Virulence Genes, Antimicrobial Resistance, and Genotypes of Campylobacter jejuni Isolated from Chicken Slaughterhouses in South Korea.

Campylobacter jejuni represents one of the leading causes of bacterial gastroenteritis in humans and is primarily linked to chicken meat contamination. In the present study, we analyzed the virulence and survival genes, antimicrobial resistance, and the clonal distribution of 50 C. jejuni isolates obtained from various sources in 14 chicken slaughterhouses across 8 provinces in South Korea from 2019 to 2022. Furthermore, we determined their genetic relatedness to human-derived isolates registered in PubMLST using multilocus sequence typing (MLST). All isolates harbored various virulence and survival genes (flhA, cadF, cdtA, cdtC, cmeA, and sodB) out of 17 tested genes, as confirmed via polymerase chain reaction analysis. Adherence factor gene virB11 was not detected in any isolate. All isolates harbored 12 or more virulence and survival genes. Antimicrobial susceptibility testing indicated that ciprofloxacin resistance was the most prevalent (84.0%), followed by nalidixic acid (82.0%) and tetracycline (52.0%) resistance. MLST analysis of the isolates revealed 18 sequence types (STs), including four new ones. Overlapping STs between chicken slaughterhouse and human-derived isolates included ST42, ST45, ST50, ST137, ST354, and ST464. Our study identified 11 clonal complexes (CCs), with CC-21 being the most prevalent in both human and chicken slaughterhouse-derived isolates. This study provides comprehensive insights into recent C. jejuni isolates from chicken slaughterhouses, including data on quinolone resistance and virulence factors. The MLST-based genetic relatedness between isolates from humans and chicken slaughterhouses in this study suggests the potential of C. jejuni transmission from chickens to humans through the food chain. This study suggests the need for improved management practices in chicken slaughterhouses to reduce the transmission of chicken slaughterhouse-derived C. jejuni to humans.

Longitudinal association between self-compassion and intuitive eating: Testing emotion regulation and body image flexibility as mediating variables.

OBJECTIVES: Growing evidence suggests that intuitive eating is associated with numerous positive mental health and well-being constructs. Understanding factors that predict intuitive eating is necessary for identifying practical targets to enhance this style of eating, yet research identifying such predictors is scarce. Self-compassion is one variable that could enhance intuitive eating because it involves the practice of healthy emotion regulation skills that may disrupt the tendency to turn to food to cope during distressing situations. The present study tested for a longitudinal association between self-compassion and intuitive eating. We also tested whether this association was mediated by indices of emotion regulation (i.e., global emotion regulation skill scores and body image flexibility). METHOD: Adult women (n = 3039) were invited to completed study measures at baseline (T1), 4-month follow-up (T2), and 8-month follow-up (T3). Path analyses were computed to test hypothesized indirect effects. RESULTS: A direct path from T1 self-compassion to T3 intuitive eating emerged, such that higher self-compassion levels predicted increased intuitive eating over time. However, this association was not mediated by T2 emotion regulation skills nor body image flexibility. CONCLUSION: Findings suggest that self-compassion may facilitate an intuitive eating style, which does not appear to be explained by certain emotion regulation skills.

Prospective voice assessment after uncomplicated thyroidectomy: A comprehensive analysis of a single centre experience.

OBJECTIVES: Voice change after uncomplicated thyroidectomy has been an important issue in the field of thyroid surgery. The aim of this study was to promote understanding of voice change after uncomplicated thyroidectomy by analysing the results for a large number of patients from a single institute. DESIGN: We retrospectively reviewed the medical records of 2879 consecutive patients who underwent thyroidectomy and voice evaluation between January 2014 and December 2019 in a single institute. All the patients had their vocal status assessed using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) scores preoperatively and at 1, 3, and 6 months postoperatively. We analysed the pattern of voice changes over time and differences in voice parameters based on clinical factors. To confirm the usefulness of the TVSQ, the correlation between TVSQ scores and objective parameters was analysed. Lastly, predictive factors for persistent voice symptoms were analysed. SETTING: Tertiary referral hospital. RESULTS: The frequency ranges and TVSQ scores exhibited significant deterioration until 6 months following surgery. Among clinical factors, the extents of thyroidectomy and neck dissection were associated with worse voice parameters. The TVSQ score was significantly correlated with objective voice parameters. The extents of thyroidectomy and neck dissection were predictive of persistent voice symptoms at 6 months after thyroidectomy. CONCLUSION: After uncomplicated thyroidectomy, most voice parameters tended to recover, but some parameters remained aggravated even at 6 months after surgery. With more extensive surgery, worse voice quality and the higher risk of persistent voice symptoms may be anticipated.

Rapid calculation of static magnetic field perturbation generated by magnetized objects in arbitrary orientations.

PURPOSE: Most previous work on the calculation of susceptibility-induced static magnetic field (B0 ) inhomogeneity has considered strictly unidirectional magnetic fields. Here, we present the theory and implementation of a computational method to rapidly calculate static magnetic field vectors produced by an arbitrary distribution of voxelated magnetization vectors. THEORY AND METHODS: Two existing B0 calculation methods were systematically extended to include arbitrary orientations of the magnetization and the magnetic field; they are (1) Fourier-domain convolution with k-space-discretized (KD) dipolar field, and (2) generalized susceptibility voxel convolution (gSVC). The methods were tested on an analytical ellipsoid model and a tilted human head model, as well as against experimentally measured B0 fields induced by a stainless-steel implant located in an inhomogeneous region of a clinical 3T MRI magnet. RESULTS: Both methods were capable of correctly calculating B0 fields inside a magnetized ellipsoid in all tested orientations. The KD method generally required a larger grid and longer computation time to achieve accuracy comparable to gSVC. Measured B0 fields due to the implant showed a good match with the gSVC-calculated fields that accounted for the spatial variation of the applied magnetic field including the radial components. CONCLUSION: Our method can provide a reliable and efficient computational tool to calculate B0 perturbation by magnetized objects under a variety of circumstances, including those with inhomogeneous magnetizing fields, anisotropic susceptibility, and a rotated coordinate system.

Laser ablation of pancreatic cancer using a cylindrical light diffuser.

Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (n = 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson's correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (p < 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer.

Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells.

Chronic liver inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Kupffer cells (KC) secrete proinflammatory and fibrogenic cytokines in response to lipopolysaccharide (LPS), and so play an important role in liver inflammation, where they induce hepatocellular damage. LPS also activates hepatic stellate cells and induces extracellular matrix deposition. In this study, we used isolated primary KC, primary hepatocytes, and primary hepatic stellate cells (HSC) to investigate whether evogliptin directly inhibits inflammatory and fibrotic signaling. We found that evogliptin inhibited LPS-induced secretion of inducible nitric oxide synthase and transforming growth factor ß (TGF-ß) from KC. Moreover, evogliptin inhibited inflammatory mediator release from hepatocytes and hepatic stellate cell activation that were induced by KC-secreted cytokines. In hepatocytes, evogliptin also inhibited LPS-induced expression of proinflammatory cytokines and fibrotic TGF-ß. In addition, evogliptin inhibited TGF-ß-induced increases in connective tissue growth factor levels and HSC activation. These findings indicate that evogliptin inhibits inflammatory and fibrotic signaling in liver cells. We also showed that the inhibitory effect of evogliptin on inflammatory and fibrotic signaling is associated with the induction of autophagy.

Prevalence, treatment patterns, and prognosis of low estrogen receptor-positive (1% to 10%) breast cancer: a single institution's experience in Korea.

PURPOSE: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer. METHODS: This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. CONCLUSION: Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease.

Thyroid Isthmusectomy with Prophylactic Central Compartment Neck Dissection is a Feasible Approach for Papillary Thyroid Cancer on the Isthmus.

BACKGROUND: The treatment for papillary thyroid cancer (PTC) has become more conservative, but still no specific guidelines exist for managing isthmic PTC. This study analyzed the outcomes from isthmusectomy in single isthmic PTC and compared it with those for patients who previously had undergone a total thyroidectomy. METHODS: An isthmusectomy with prophylactic central compartment neck dissection (pCCND) was planned for a single isthmic PTC between 2014 and 2018 (isthmusectomy group). For cases with gross extrathyroidal extension (ETE) or multiple nodal metastasis, the procedure was converted to a total thyroidectomy. The study analyzed the characteristics and outcomes of the isthmusectomy group. Additionally, the results were compared with those of the isthmusectomy-feasible group who met the eligibility criteria for isthmusectomy among total thyroidectomies performed between 2009 and 2013. RESULTS: Of the 90 patients in the isthmusectomy group, 81 received isthmusectomy and 9 had conversion to a total thyroidectomy. Microcarcinoma occurred in 72 cases and gross ETE in 3 cases. One patient showed occult satellite cancer, and seven patients showed more than five metastatic nodes. Transient hypocalcemia developed in five and patients and permanent hypocalcemia in one patient with total thyroidectomy. Of 46 patients who began hormone replacement postoperatively, 13 completely stopped taking medication during the follow-up period. Metachronous PTC was diagnosed for one patient 12 months after isthmusectomy. The isthmusectomy group and the isthmusectomy-feasible group showed similar clinicopathologic properties including multifocality, ETE, and nodal metastasis. However, the isthmusectomy group showed significantly less transient or permanent hypocalcemia and thyroid hormone dependency. CONCLUSIONS: Isthmusectomy with pCCND may be a feasible alternative for properly selected isthmic PTC, resulting in a better quality of life than total thyroidectomy.

Rising prevalence of colonic diverticulosis in a westernized multi-ethnic Asian community.

BACKGROUND AND AIM: Singapore is a multi-ethnic country that has undergone rapid development over the last few decades, with increasing influence of western culture, and faces an aging population. Previously, a varying prevalence of colonic diverticulosis (CD) was reported by a few small studies. This study aims to evaluate the prevalence of CD in Singapore and identify associations with common gastrointestinal symptoms and risk factors. METHODS: We reviewed retrospective data of 20 395 consecutive colonoscopies performed from 2006 to 2016 for presence of CD and indications of screening, diarrhea, constipation, and abdominal pain. RESULTS: The prevalence of CD progressively increased from 2006 to 2016 (14.9% vs 23.9%, adjusted trend < 0.001), with an overall prevalence of 19.6%. Patients with CD were older and had higher body mass index (BMI). CD was significantly more prevalent in Chinese compared with Malay and Indian races (20.5% vs 18.9% vs 15.5%, P < 0.05), and in male patients compared with female patients (21.5% vs 17.6%, P < 0.05). Right-sided CD was more common than left-sided or pan diverticulosis (16.2% vs 8.3% vs 4.8%, P < 0.05). Age [odds ratio (OR), 1.060; 95% confidence interval (CI), 1.052-1.068], BMI (OR, 1.051; 95% CI, 1.028-1.075), male gender (OR, 1.317; 95% CI, 1.084-1.600), and abdominal pain (OR, 1.409; 95% CI, 1.168-1.699) were positively associated, while constipation (OR, 0.566; 95% CI, 0.452-0.709) was negatively associated with CD. CONCLUSION: The prevalence of CD in Singapore has progressively increased over the last decade and is associated with older age, higher BMI, and abdominal pain. These findings may provide insights for healthcare resource planning in the region.

Comparison of long-term surgical outcome between transaxillary endoscopic and conventional open thyroidectomy in patients with differentiated thyroid carcinoma: a propensity score matching study.

BACKGROUND: There is an increased use of endoscopic thyroidectomy (ET), including robotic-assisted thyroidectomy (RT), to avoid postoperative scars on the anterior neck. The objective of this study was to compare the surgical and oncologic outcomes between ET and conventional open thyroidectomy (COT) for differentiated thyroid carcinoma (DTC). METHODS: We reviewed 4129 patients with DTC who underwent thyroid lobectomy at Seoul St. Mary's Hospital (Seoul, Korea) from January 2009 to December 2014. Patients were categorized according to the type of surgery and statistically compared using propensity score matching analysis. RESULTS: The mean operation time was significantly longer in the ET group than in the OT group (101.2 ± 26.2 min vs. 86.4 ± 27.0 min, p < 0.001). The number of harvested lymph nodes was significantly lower in the ET group than in the OT group (5.5 ± 4.2 vs. 8.3 ± 6.2, p < 0.001). There was no significant difference in the recurrence rate between the two groups (p = 0.879). Kaplan-Meier analysis revealed no significant difference in the disease-free survival after propensity score matching (p = 0.811). The mean follow-up duration was 90.4 ± 21.0 months. CONCLUSIONS: Transaxillary ET including RT for DTC is a safe and feasible alternative to COT with a cosmetically desirable outcome. Further studies are required to confirm our results.

Kahweol Induces Apoptosis in Hepatocellular Carcinoma Cells by Inhibiting the Src/mTOR/STAT3 Signaling Pathway.

Kahweol, a coffee-specific diterpene, induces apoptosis in human cancer cells, and some targets of kahweol-mediated apoptosis have been identified. However, the specific apoptotic effects and mechanism of action of kahweol in hepatocellular carcinoma (HCC) cells are unknown. This study was performed to investigate the molecular mechanism by which kahweol induces apoptosis in HCC cells. The Src pathway is associated with apoptosis in cancer. In this study, we found that kahweol induces apoptosis by inhibiting phosphorylation of Src, and also inhibiting p-mTOR and p-STAT3. Therefore, we suggest that kahweol is a potent inhibitor of HCC cell growth.

In Vitro and In Vivo Protective Effects of Lentil (Lens culinaris) Extract against Oxidative Stress-Induced Hepatotoxicity.

Excessive oxidative stress plays a role in hepatotoxicity and the pathogenesis of hepatic diseases. In our previous study, the phenolic extract of beluga lentil (BLE) showed the most potent in vitro antioxidant activity among extracts of four common varieties of lentils; thus, we hypothesized that BLE might protect liver cells against oxidative stress-induced cytotoxicity. BLE was evaluated for its protective effects against oxidative stress-induced hepatotoxicity in AML12 mouse hepatocytes and BALB/c mice. H2O2 treatment caused a marked decrease in cell viability; however, pretreatment with BLE (25-100 µg/mL) for 24 h significantly preserved the viability of H2O2-treated cells up to about 50% at 100 µg/mL. As expected, BLE dramatically reduced intracellular reactive oxygen species (ROS) levels in a dose-dependent manner in H2O2-treated cells. Further mechanistic studies demonstrated that BLE reduced cellular ROS levels, partly by increasing expression of antioxidant genes. Furthermore, pretreatment with BLE (400 mg/kg) for 2 weeks significantly reduced serum levels of alanine transaminase and triglyceride by about 49% and 40%, respectively, and increased the expression and activity of glutathione peroxidase in CCl4-treated BALB/c mice. These results suggest that BLE protects liver cells against oxidative stress, partly by inducing cellular antioxidant system; thus, it represents a potential source of nutraceuticals with hepatoprotective effects.

Perspectives of e-health interventions for treating and preventing eating disorders: descriptive study of perceived advantages and barriers, help-seeking intentions, and preferred functionality.

PURPOSE: Digital interventions that consider end-user needs, preferences, and concerns may address suboptimal rates of e-health uptake, usage, and engagement. We explored target-user perspectives of e-health treatment and prevention programs for eating disorders (EDs), with a focus on investigating (1) perceived advantages and barriers of e-health; (2) help-seeking intentions; and (3) preferences for different digital functionality, device types, and content-delivery formats. METHODS: Survey data were analysed from 722 community-based participants. Participants were categorized into one of four groups based on symptom presentation and severity, ranging from low risk to probable bulimia nervosa or binge-eating disorder. RESULTS: e-health advantages that received the highest endorsement (~ 84%) were "always there in times of need" and "travel not required". e-health barriers that received the highest endorsement (~ 50%) were concerns about data privacy and the accuracy of content presented. Nearly three-quarters reported an intention to use an e-health platform for preventing or treating EDs. Preference ratings were highest for programs to be available on all digital devices (relative to restricting the program to one type of device) and for content to be presented via graphics and video tutorials (rather than audio-based). e-health functionality that received highest preference ratings (~ 80%) were added clinician support, tailored feedback, strategies to change unhelpful ED thoughts, screening scales to assess symptoms, ED psychoeducation, and just-in-time intervention prompts. Preference and intention ratings were strikingly similar across all subgroups. CONCLUSION: Findings may inform the development and design of e-health platforms that meet the needs of people at different stages of an ED. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Thiol-disulfide status regulates quality control of prion protein at the plasma membrane.

Rapid endoplasmic reticulum (ER) stress-induced export (RESET) is undoubtedly beneficial in that it eliminates misfolded prion protein (PrP) from a stressed ER. Considering that RESET induces rapid endocytosis of misfolded PrP for degradation, it is questionable whether RESET is beneficial when its product amount overwhelms the capacity of subsequent clearance pathways. We require a strategy to monitor the endocytic flux rate of misfolded PrPs. Here, we stabilized misfolded PrPs by inserting red fluorescent protein (RFP) and indirectly determined this rate by monitoring the lysosomal free RFP. We discovered a surveillance mechanism that limits endocytosis of misfolded PrPs through plasma membrane quality control (pmQC). pmQC was regulated by the thiol-disulfide status of misfolded PrPs and consequently accumulates nonpathogenic PrP variants at the plasma membrane. This variant alleviated prion proteotoxicity induced by persistent RESET. Thus, PrP endocytosis is regulated by pmQC to ensure the safety of endolysosomal pathway from persistent internalization of misfolded PrP.-Lee, D., Lee, S., Shin, Y., Song, Y., Kang, S.-W. Thiol-disulfide status regulates quality control of prion protein at the plasma membrane.

How Can We Predict the Recovery from Pitch Lowering After Thyroidectomy?

BACKGROUND: Some of patients are suffered from pitch lowering of voice after thyroidectomy. We sought to identify factors predictive of a recovery from lowered pitch voice after thyroid surgery. METHODS: We retrospectively reviewed the records of 133 patients who underwent total thyroidectomy to treat papillary carcinoma between January 2012 and February 2013. Of these, we enrolled 78 who exhibited a lower-pitched voice (SFF fall > 12 Hz) at 2 weeks post-operatively than pre-operatively and investigated pitch recovery after 3 months. We subclassified patients into recovery and non-recovery groups and compared videostroboscopic findings, acoustic voice data, and thyroidectomy-related voice questionnaire scores pre-operatively and 2, 8, and 12 weeks post-operatively. RESULTS: Vocal cord asymmetry on videostroboscopic examination at 2 weeks post-operatively (odds ratio 19.056, p = 0.001*) was more frequent in the non-recovery group. In acoustic analysis, mean pre-operative SFF was higher in the non-recovery group than the recovery group (190.9 ± 27.5 and 180.9 ±  24.6 Hz, respectively; p = 0.030*). Also, a reduction in the SFF of > 19.6 Hz, at 2 weeks post-operatively versus pre-operatively, predicted non-recovery of pitch-lowering in patients with reduced SFF within post-operative 3 months, with 72.0% sensitivity and 71.2% specificity. After 6 months of follow-up, no patient who exhibited an SFF fall > 19.6 Hz recovered to within 10 Hz of the pre-operative value. CONCLUSION: A reduction in the speaking fundamental frequency (SFF) > 19.6 Hz at 2 weeks post-operatively predicted persisting lowering of voice pitch after thyroidectomy among those with lower-pitched voices after surgery. Pre-operative high SFF and post-operative stroboscopic findings including vocal cord asymmetry at 2 weeks post-operatively also predicted persisting lowering of voice pitch for 3 months.

Design of Advanced Polymeric Hydrogels for Tissue Regenerative Medicine: Oxygen-Controllable Hydrogel Materials.

Engineered polymeric hydrogels have been extensively utilized in tissue engineering and regenerative medicine because of their biocompatibility, tunable properties, and structural similarity in their native extracellular microenvironment. The native extracellular matrix (ECM) has been implicated as a crucial factor in the regulation of cellular behaviors and their fate. The emerging trend in the design of hydrogels involves the development of advanced materials to precisely recapitulate the native ECM or to stimulate the surrounding tissues via physical, chemical, or biological stimuli. The ECM presents various parameters such as ECM components, soluble factors, cell-to-cell and cell-to-matrix interactions, physical forces, and physicochemical environments. Among these environmental factors, oxygen is considered as an essential signaling molecule. In particular, abnormal oxygen tension such as a lack of oxygen (defined as hypoxia) and an excess supply of oxygen (defined as hyperoxia) plays a pivotal role during early vascular development, tissue regeneration and repair, and tumor progression and metastasis. In this chapter, we discuss how engineered polymeric hydrogels serve as either an artificial extracellular microenvironment to create engineered tissues or as an acellular matrix to stimulate the native tissues for a wide range of biomedical applications including tissue engineering and regenerative medicine, wound healing, and engineered disease models. Specifically, we focus on emerging technologies to create advanced polymeric hydrogel materials that accurately mimic or stimulate the native ECM.

Use of a Phosphatase-Like DT-Diaphorase Label for the Detection of Outer Membrane Vesicles.

DT-diaphorase (DT-D) is known to mainly catalyze the two-electron reduction of quinones and nitro(so) compounds. Detection of Gram-negative bacterial outer membrane vesicles (OMVs) that contain pyrogenic lipopolysaccharides (LPSs, also called endotoxins) is required for evaluating the toxic effects of analytical samples. Here, we report that DT-D has a high dephosphorylation activity: DT-D catalyzes reductive dephosphorylation of a phosphate-containing substrate in the presence of NADH. We also report that sensitive and simple OMV detection is possible with a sandwich-type electrochemical immunosensor using DT-D and two identical LPS-binding antibodies as a catalytic label and two sandwich probes, respectively. The absorbance change in a solution containing 4-nitrophenyl phosphate indicates that dephosphorylation occurs in the presence of both DT-D and NADH. Among the three phosphate-containing substrates [4-aminophenyl phosphate, ascorbic acid phosphate, and 1-amino-2-naphthyl phosphate (ANP)] that can be converted into electrochemically active products after dephosphorylation, ANP shows the highest electrochemical signal-to-background ratio, because (i) the dephosphorylation of ANP by DT-D is fast, (ii) the electrochemical oxidation of the dephosphorylated product (1-amino-2-naphthol, AN) is rapid, even at a bare indium-tin oxide electrode, and (iii) two redox cycling processes significantly increase the electrochemical signal. The two redox cycling processes include an electrochemical-enzymatic redox cycling and an electrochemical-chemical redox cycling. The electrochemical signal in a neutral buffer (tris buffer, pH 7.5) is comparable to that in a basic buffer (tris buffer, pH 9.5). When the immunosensor is applied to the detection of OMV from Escherichia coli, the detection limit is found to be 8 ng/mL. This detection strategy is highly promising for the detection of biomaterials, including other extracellular vesicles.

Distinct Clinical Manifestations of Thyroid Cancer After Hematopoietic Stem Cell Transplantation.

BACKGROUND: The incidence of a secondary solid malignancy after hematopoietic cell transplantation (HCT) is increasing in long-term survivors. OBJECTIVE: The aim of this study was to compare the clinicopathological characteristics of HCT recipients with secondary thyroid cancer (STC), with those of non-HCT thyroid cancer patients. METHODS: We retrospectively investigated 5184 patients who received HCT between 1983 and 2016. Of these, 18 patients developed STC and underwent thyroidectomy due to differentiated thyroid cancer. We compared the clinicopathological characteristics of post-HCT thyroid cancer patients (post-HCT group) with those of a primary differentiated thyroid carcinoma cohort (cohort group) from Seoul St. Mary's Hospital. RESULTS: The mean ages at HCT and thyroidectomy after HCT were 22.0 and 31.8 years, respectively, and the median time interval between HCT and thyroidectomy was 5 years (range 1-16). Compared with the cohort group, the post-HCT group was younger at cancer onset and frequently had a palpable mass at initial diagnosis. The post-HCT group had more aggressive features, including larger tumor size, frequent extrathyroidal extension, lymphatic invasion, perineural invasion, and frequent lateral neck node metastasis and distant metastasis, relative to the cohort group; however, most patients (83.2%) in the post-HCT group were stage I or II. Additionally, BRAF V600E mutation was less frequent in the post-HCT group. CONCLUSIONS: We found that STC after HCT showed younger presentation and more aggressive clinical presentation. Therefore, a policy of regular screening, including neck ultrasound examination, may promote early detection and treatment in HCT recipients.

Comparison of efficacy and complications between radiofrequency ablation and repeat surgery in the treatment of locally recurrent thyroid cancers: a single-center propensity score matching study.

PURPOSE: To compare the efficacy and complication rates of radiofrequency ablation (RFA) and repeat surgery in the treatment of locally recurrent thyroid cancers. MATERIALS AND METHODS: A total of 221 patients with locally recurrent thyroid cancers who underwent either RFA (n = 96) or repeat surgery (n = 125) between March 2008 and March 2017 were retrospectively enrolled (range of follow-up, 1-10 years). Each cohort consisted of 70 patients after propensity score adjustment. Patients with more than three recurrent lesions were excluded. The primary and secondary end points were recurrence-free survival and complication rates, respectively. Recurrence-free survival curves were compared via the log-rank test. The complications-voice changes, hypocalcemia, and immediate procedural complications-were compared between the groups. In addition, pretreatment serum thyroglobulin (Tg) levels and those at the last follow-up were also compared between the two groups to examine therapeutic efficacy. RESULTS: After propensity score matching, both groups showed no significant differences in baseline characteristics. The recurrence-free survival rates were comparable between the RFA and surgery groups (p = .2). There were no significant differences in mean serum Tg levels and their mean decrease after treatment between the groups (p = .891 and p = .963, respectively). Immediate procedural complications and voice changes also showed no significant between-group differences (p = .316, p = .084, respectively). Hypocalcemia occurred only in the repeat surgery group (n = 18). Overall complications were significantly more frequent in the repeat surgery group (RFA, n = 7; surgery, n = 27; p < .001). CONCLUSION: RFA may be an effective and safe alternative to repeat surgery in the treatment of a small number of locally recurrent thyroid cancers.

Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier. OBJECTIVE: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis. METHODS: We identified and generated reporter proteins conjugated to astrotactin 1-derived peptide (AP), a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multiphoton confocal microscopy. We also generated a recombinant therapeutic protein, AP-recombinant protein tyrosine phosphatase (rPTP), consisting of the phosphatase domain of the T-cell protein tyrosine phosphatase conjugated to AP. The immunomodulatory function of AP-rPTP was confirmed in splenocytes on cytokine stimulation and T-cell receptor stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP transdermal delivery in patients with oxazolone-induced contact hypersensitivity, ovalbumin-induced AD-like, and imiquimod-induced psoriasis-like skin inflammation models. RESULTS: AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited phosphorylated signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell activation and proliferation. Transcutaneous administration of AP-rPTP through the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both AD-like and psoriasis-like dermatitis models. CONCLUSION: We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis.