Effect of orodispersible hyaluronic acid film on palatal mucosa wound healing.

OBJECTIVE: The objective of the study was to evaluate the healing effect of hyaluronic acid films on palatal wounds. MATERIALS AND METHODS: After making 5-mm diameter palatal wounds, 72 rats were randomly assigned to three groups: control, hyaluronic acid gel, and hyaluronic acid film. The animals were sacrificed at 3, 7, and 21 days after the experiment. Clinical, histological, and RT-PCR analyses were performed. Human ex vivo oral mucosa models were used. Histological analysis and pan-cytokeratin staining were performed at 5 days after wound creation. RESULTS: In rat model, both gels and films showed favorable healing on Days 3 and 7 compared with healing in the control (p < 0.05). Film showed remarkable VEGF and α-SMA expression than did the others (p < 0.05). Immunohistochemical analysis showed that film exhibited significantly lower CD68 and greater α-SMA and vimentin expression levels than those in the others (p < 0.05). In human model, re-epithelialization rate of film group was significantly higher than that of the others. Complete epithelial regeneration was confirmed only in film group using pan-cytokeratin staining. CONCLUSIONS: Within the limits of this study, hyaluronic acid film outperformed gels in terms of palatal wound healing in both models.

Effect of intra-alveolar delivery of Frondoside A on inflammatory response of delayed tooth replantation.

BACKGROUND/AIM: Frondoside A is a sea cucumber extract which is well known for its anti-inflammatory and immunomodulatory properties. The purpose of this study was to evaluate the effect of Frondoside A application in the alveolar socket on inflammatory responses after delayed replantation in rat teeth. MATERIALS AND METHODS: Human periodontal ligament cells were cultured and exposed to Frondoside A. Cell-counting kit-8 assay was performed to evaluate the cell viability and nitric oxide assay was performed to assess the anti-inflammatory effect of Frondoside A. Molars were extracted from 32 Sprague-Dawley rats and randomly divided into control and Frondoside A groups. After 30 min of extra-oral dry time, molars were replanted. In the Frondoside A group, Frondoside A solution was applied in the alveolar socket before replantation. The animals were sacrificed after 28 days and histologically and immunohistochemically evaluated. RESULTS: 0.5 µM Frondoside A showed higher cellular viability at 6 h and lower production of nitric oxide compared with other Frondoside A solutions (p < .05). The Frondoside A group demonstrated lower inflammatory resorption scores in both middle 1/3 and apical 1/3 of root compared to the control group (p < .05). The Frondoside A group showed lower levels of expression in both cathepsin K and CD45 compared with the control group (p < .05). CONCLUSIONS: Within the limits of this study, intra-alveolar delivery of Frondoside A alleviates inflammatory root resorption in delayed replantation of rat teeth.

Risk prediction of the metabolic syndrome using TyG Index and SNPs: a 10-year longitudinal prospective cohort study.

TyG (triglyceride and glucose) index using triglyceride and fasting blood glucose is recommended as a useful marker for insulin resistance. To clarify whether the TyG index is a marker for predicting metabolic syndrome (MetS) and to investigate the importance of single-nucleotide polymorphisms (SNPs) in MetS diagnosis. From 2001 to 2014, a longitudinal prospective cohort study of 3580 adults aged 40-70 years was conducted. The area under the receiver operating characteristic curves (AUROC) and Youden index (YI) was calculated to assess the diagnostic value. During the 14-year follow-up, 1270 subjects developed MetS. Five SNPs in four genes (BUD13 rs10790162, ZPR1 rs2075290, APOA5 rs2266788, APOA5 rs2075291, and MKL1 rs4507196) significantly correlated with susceptibility to MetS (p < 0.00005). The areas under the curve of TyG index and HOMA-IR were 0.854 (95% confidence interval [CI], 0.841-0.867) and 0.702 (95% CI, 0.684-0.721), respectively. Despite no statistical significance, AUROC and YI were increased when MetS was diagnosed using TyG index and the five SNPs. TyG index might be useful for identifying individuals at high risk of developing MetS. The combination of TyG index and SNPs showed better diagnostic accuracy than TyG index alone, indicating the potential value of novel SNPs for MetS diagnosis.

Lighting up the stressed ER.

Balancing the capacity for protein maturation with changes in protein flux through the endoplasmic reticulum (ER) is crucial for maintaining ER homeostasis. In this issue, Merksamer et al. (2008) exploit a redox-sensitive fluorescent protein to monitor the environment inside the ER of living yeast, illuminating how this organelle responds to different perturbations.

Preparation of Porous Hydroxyethyl Cellulose Materials to Utilize Lactic Acid with Vacuum-Assisted Process.

For the first time, we succeeded in manufacturing a 2-hydroxyethyl cellulose (HEC)-based composite membrane with improved thermal stability, for use as a battery separator, coating a HEC polymer solution to a polypropylene (PP) support and using a vacuum-assisted process. A HEC polymer solution was prepared by utilizing HEC and lactic acid (LA) as a plasticizer. A vacuum-assisted process was used to move ethanol, which a mobile phase to permeate a plasticized region in the HEC polymer side for pore formation. The pores formed with uniform nano sizes, and areas in which some large pores formed were observed. The thermal stability of the composites was measured using TGA. The thermal decomposition temperatures were measured at about 250 °C for the neat HEC, about 210 °C for the HEC/LA film, and about 335 °C for the HEC/LA/PP membrane before the process. After the vacuum-assisted process, the first and second thermal decomposition were observed at about 360 °C and 450 °C, respectively. The HEC/LA/PP membrane after the process showed greater thermal stability than before the process. This means that the adhesion between the HEC polymer and the PP support was created through the rearrangement of the HEC chain, as LA escaped after the process, and it was seen indirectly that the mechanical strength was enhanced. In particular, the surface of the membrane was observed by SEM to investigate whether the HEC penetrated into the PP to block its pores, and whether the HEC region collapsed. Furthermore, the interaction of the HEC chain with the additives and the rearrangement of the HEC was confirmed using FT-IR. As a result, we demonstrated that the mechanical strength and thermal stability of the manufactured HEC/LA/PP membrane were enhanced.

Evaluation of delphinidin as a storage medium for avulsed teeth.

BACKGROUND: Delphinidin (DP), an anthocyanidin found in blueberries, has antioxidant and anti-inflammatory effects. This study aimed to investigate the efficacy of DP as a storage medium for avulsed teeth. METHODS: Human periodontal ligament cells were cultured and exposed to DP solution (10, 50, and 100 µM), Dulbecco's modified Eagle's medium, Hank's balanced salt solution and tap water. Cell counting kit-8 assays were performed after 0.5, 1, 6, and 24 h to measure the cell viability. Nitric oxide assays and gelatin zymography were performed to evaluate the anti-inflammatory effects of DP. Reverse transcription-polymerase chain reaction was used to determine the expression levels of inflammatory cytokines. RESULTS: The viability of periodontal ligament cells was greatest at 100 µM DP. At 1 h, 100 µM DP decreased nitric oxide synthesis (p < .0167). Matrix metallopeptidase-9 activity was inhibited by DP in a dose-dependent manner (p < .0167). Moreover, treatment with 100 µM DP decreased the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 in periodontal ligament cells (p < .0167). CONCLUSIONS: Within the limits of this study, DP preserved the viability and suppressed the inflammatory response of periodontal ligament cells. These findings suggest that DP could be promising for preservation of avulsed teeth.

Bisphenol A release from commercially available 3-dimensionally printed resins and human cell apoptosis to bisphenol A: an in-vitro study.

Bisphenol A (BPA) from dental materials may be linked to children's health issues. This study aimed to assess the release of BPA from commercially available 3-dimensional (3D)-printed resin materials and evaluate BPA-related apoptotic effects on human periodontal ligament cells and gingival fibroblasts. Commercially available 3D-printed resin materials for prosthodontic use were selected as follows: NextDent C&B MFH (3D Systems, Rock Hill, SC, USA), DIOnavi-P. MAX (Dio Co., Busan, Korea), and DIOnavi-Denture02 (Dio Co., Busan, Korea). Identical cuboidal samples (1 cm × 1 cm × 0.5 cm) were printed from the materials and cured. BPA release was assessed using liquid chromatography/mass spectrometry (LC/MS). In addition, human gingival fibroblasts and periodontal ligament cells were exposed to various BPA solutions based on the LC/MS results. Cell Counting kit-8 (CCK-8) and real-time polymerase chain reaction analyses were performed to evaluate BPA-related apoptotic effects. The LC/MS analysis confirmed that none of the 3D-printed resin materials released BPA after curing. Both human gingival fibroblasts and periodontal ligament cells showed lower viability after BPA exposure. Regarding apoptosis-related gene expression, Caspase10 (CASP10) expression in periodontal ligament cells was significantly different in the BPA solutions (p < 0.05). The expression of BAX and Capspase8 (CASP8) in gingival fibroblasts was significantly increased by BPA in a dose-dependent manner (p < 0.05). Within the limitations of this study, the 3D-printed resin materials were not found to release BPA. This finding implies that 3D-printed resin materials are not associated with potential BPA-related risks in children.

Robotic Adrenalectomy Using the da Vinci SP Robotic System: Technical Feasibility Comparison with Single-Port Access Using the da Vinci Multi-arm Robotic System.

BACKGROUND: Laparoscopic adrenalectomy is the gold standard for adrenal tumor; however, robotic adrenal surgery has gained interest recently. For minimally invasive surgeries, we first reported on robotic adrenalectomy using a single-port access performed using the da Vinci multi-arm robotic system (RA-SA) in 2011. Since its introduction in 2018, we first performed robotic adrenalectomy using the da Vinci SP robotic system in 2020. OBJECTIVE: We aimed to introduce the novel single-port robotic system (RA-SP) for adrenalectomy and evaluate its technical feasibility by comparing it with the surgical outcomes of patients who underwent robotic adrenalectomy using the RA-SA. METHODS: Eight patients who underwent robotic adrenalectomy using the RA-SP from February 2020 to June 2021 were compared with 11 patients who underwent RA-SA from 2011 to 2015 by a single surgeon. RESULTS: The two groups were similar in age, sex, body mass index, type of operation, and final pathologic diagnosis. Despite no significant differences, RA-SP resulted in moderately less mean operation time, estimated blood loss, and length of hospitalization. CONCLUSIONS: The Da Vinci SP robotic system is a novel, safe, and feasible technique to improve the convenience of operation and cosmetic effect for adrenalectomy.

Robotic transaxillary lateral neck dissection for thyroid cancer: learning experience from 500 cases.

BACKGROUND: Differentiated thyroid carcinoma with lateral neck lymph node metastasis requires aggressive operative intervention, including lateral neck dissection. Although several robotic approaches have made precise surgery for thyroid cancer possible, few centers have expanded the technique for application to lateral neck dissections. This study aimed to demonstrate the technical feasibility, cosmetic effectiveness, and safety of robotic transaxillary lateral neck dissection (RTLND) using the da Vinci system. METHODS: From January 2008 to July 2019, 500 patients diagnosed with thyroid cancer with lateral neck node metastasis underwent RTLND. The clinicopathologic characteristics and surgical outcomes were retrospectively reviewed. RESULTS: All operations were performed successfully without open conversion. As the primary operation for thyroid cancer, 476 (95.2%) patients underwent unilateral or bilateral RTLND, including robotic total thyroidectomy. The remaining 24 patients (4.8%), all of whom had a recurrence, also underwent RTLND with additional procedures, if needed. The mean operation time for the 500 operations was 293.71 ± 67.22 min. Only five cases had recurrence and required further treatment. CONCLUSIONS: RTLND is technically feasible and safe through the precise manipulation of robotic instruments. While this method is thorough and provides safe and effective surgical outcomes, it also offers the additional advantage of being minimally invasive.

Single-port transaxillary robotic thyroidectomy (START): 200-cases with two-step retraction method.

BACKGROUND: This study aims to report the results of a pioneering clinical study using the single-port transaxillary robotic thyroidectomy (START) for 200 patients with thyroid tumor and to introduce our novel two-step retraction method. METHODS: START was performed on consecutive 200 patients using the da Vinci Single-Port (SP) robot system from January 2019 to September 2020 at the Yonsei University Health System, Seoul, Korea. The novel two-step retraction technique, in which a 3.5 cm long incision is made along the natural skin crease, was used for the latter 164 patients. The surgical outcome and invasiveness of the SP two-step retraction method were analyzed. RESULTS: Among the 200 cases who underwent START, 198 were female and 2 were male, with a mean age of 34.7 (range: 13-58 years). Thyroid lobectomy was performed for 177 patients and total thyroidectomy was performed for 23 patients. Ten patients had benign thyroid nodules, whereas the other 190 had thyroid malignancy. The mean body mass index (BMI) was 22.2 ± 3.7 kg/m2 (range: 15.9-37.0 kg/m2). All of the operations were performed successfully without any open conversions, and patients were discharged on postoperative day 3 or 4 without significant complication. The mean operative time for thyroid lobectomy with the two-step retraction method was 116.69 ± 23.23 min, which was similar to that in the conventional robotic skin flap method (115.33 ± 17.29 min). We could minimize the extent of the robotic skin flap dissection with the two-step retraction method. CONCLUSIONS: START is a practical surgical method. By employing the new two-step retraction method, we can maximize the cosmetic and functional benefits for patients and reduce the workload fatigue of surgeons by increasing robotic dependency.

Safety and Feasibility of Robotic Transaxillary Thyroidectomy for Graves' Disease: A Retrospective Cohort Study.

BACKGROUND: Despite the increase in experience and understanding of robotic thyroidectomy, its application for Graves' disease (GD) remains controversial. This study aimed to assess the safety and feasibility of robotic transaxillary thyroidectomy (RTT) for GD in comparison with the conventional open thyroidectomy (open group: OG) approach. METHODS: A total of 192 patients who underwent surgical resection for GD were retrospectively reviewed. Among them, 51 patients underwent RTT and the remaining 141 patients were in the conventional OG. RESULTS: All robotic operations were performed successfully without open conversion. Patients who underwent RTT were significantly younger (P < 0.001) and predominantly of the female sex. Operative time was longer for RTT than for the OG (182.5 ± 58.1 vs. 112.0 ± 29.5; P < 0.001). The mean intraoperative blood loss was not statistically different between RTT and the OG (113.3 ± 161.6 vs. 95.3 ± 209.1, P = 0.223). The mean weight of the resected thyroid was reduced in those who underwent RTT compared with open thyroidectomy (P = 0.033). The overall complication rate for RTT and open thyroidectomy was not significantly different (33.3% vs. 22.7%, P = 0.135). In RTT, the most common complication was transient hypocalcemia (21%). Permanent hypocalcemia and recurrent laryngeal nerve injury occurred in only one patient in each group. The weight of the resected thyroid was not related to the incidence of complications in patients receiving RTT. CONCLUSIONS: Considering excellent cosmesis, findings of this study support the safety and feasibility of RTT. Nevertheless, it should be performed by expert surgeons with extensive robotic surgery experience.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. METHODS: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). RESULTS: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. CONCLUSION: We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Interactions of Ag Particles Stabilized by 7,7,8,8-Tetracyanoquinodimethane with Olefin Molecules in Poly(ether-block-amide).

In this study, to use a stabilized carrier, silver nanoparticles (AgNPs) were used as carriers and electron acceptors were added to activate the surface of AgNPs as olefin carriers. In addition, poly(ether-block-amide) (PEBAX), consisting of polyamide (hard segments) and polyether (soft segments), was investigated for the correlation of the between-segments ratio related to the stability of AgNPs and separation performance. As a result, contrary to the expectation that high permeance would be observed in PEBAX-1657/AgNPs/7,7,8,8-tetracyanoquinodimethane (TCNQ) membrane, which had a higher ratio of polyether soft segment, the PEBAX-5513/AgNPs/TCNQ membrane, which had a relatively high proportion of polyamide, showed a higher permeance without difference in selectivity. These unexpected data were attributable to the fact that the relatively abundant amount of PA groups in PEBAX-5513 was able to stabilize and positively polarize the surface of AgNPs, resulting in the stabilized and high performance of olefin separation.

Identification of Multiple Hub Genes in Acute Kidney Injury after Kidney Transplantation by Bioinformatics Analysis.

Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein-protein interaction network. Results: Finally, we identified 137 differentially expressed genes (59 upregulated genes and 16 downregulated genes). AKAP12, AMOT, C3AR1, LY96, PIK3AP1, PLCD4, PLCG2, TENM2, TLR2, and TSPAN5 were filtrated by the hub genes related to the development of post-transplant AKI from the Protein-Protein Interaction (PPI) network. Conclusions: This may provide important evidence of the diagnostic and therapeutic biomarker of AKI.

Implications of US radiomics signature for predicting malignancy in thyroid nodules with indeterminate cytology.

OBJECTIVES: The purpose of this study was to evaluate the role of the radiomics score using US images to predict malignancy in AUS/FLUS and FN/SFN nodules. METHODS: One hundred fifty-five indeterminate thyroid nodules in 154 patients who received initial US-guided FNA for diagnostic purposes were included in this retrospective study. A representative US image of each tumor was acquired, and square ROIs covering the whole nodule were drawn using the Paint program of Windows 7. Texture features were extracted by in-house texture analysis algorithms implemented in MATLAB 2019b. The LASSO logistic regression model was used to choose the most useful predictive features, and ten-fold cross-validation was performed. Two prediction models were constructed using multivariable logistic regression analysis: one based on clinical variables, and the other based on clinical variables with the radiomics score. Predictability of the two models was assessed with the AUC of the ROC curves. RESULTS: Clinical characteristics did not significantly differ between malignant and benign nodules, except for mean nodule size. Among 730 candidate texture features generated from a single US image, 15 features were selected. Radiomics signatures were constructed with a radiomics score, using selected features. In multivariable logistic regression analysis, higher radiomics score was associated with malignancy (OR = 10.923; p < 0.001). The AUC of the malignancy prediction model composed of clinical variables with the radiomics score was significantly higher than the model composed of clinical variables alone (0.839 vs 0.583). CONCLUSIONS: Quantitative US radiomics features can help predict malignancy in thyroid nodules with indeterminate cytology.

Feasibility and safety of the posterior retroperitoneoscopic approach in the resection of aortocaval and infrarenal paraganglioma: a single-center experience.

BACKGROUND: The posterior retroperitoneoscopic approach (PRA) has been under attention as a method for resection of paraganglioma (PGL) for the past few years. However, only a few studies have explored the effectiveness and safety of the PRA for aortocaval and infrarenal PGL resection. METHODS: We designed this retrospective study to investigate the safety and effectiveness of the PRA for aortocaval and infrarenal PGL resection in a single center. We retrospectively reviewed the medical records of patients who underwent PRA for PGL resection at our medical center from January 2006 to March 2021. Eight patients were enrolled, of whom six had aortocaval PGL. We investigated the surgical outcomes of enrolled patients. RESULTS: The locations of the tumors in relation to the renal vein were: suprarenal in two (25.0%) patients, at the renal vein level in three (37.5%) patients, and infrarenal in three (37.5%) patients. The mean operative time of the enrolled patients was 101.5 ± 39.1 min. The mean postoperative stay was 3.5 ± 1.5 days, and the estimated blood loss was 31.3 ± 51.4 ml. There was one minor complication (chyle leakage), and two hypotensive events occurred during the surgery. Focusing on the results of the renal vein level and infrarenal PGL resection, the mean operative time, mean postoperative stay, and estimated blood loss of the patients were 109.2 ± 41.3 min, 3.5 ± 1.8 days, and 41.7 ± 56.4 ml, respectively. CONCLUSION: The PRA for aortocaval and infrarenal PGL resection is feasible and safe. Additional data analysis and long-term follow-up are needed in the future.

HLA-G 14bp Ins/Del Polymorphism in the 3'UTR Region and Acute Rejection in Kidney Transplant Recipients: An Updated Meta-Analysis.

Background and Objectives: Acute kidney injury (AKI) affects the survival rate of kidney transplant organs and patients. Acute rejection (AR) due to AKI may lead to kidney transplantation failure. It is known that there is a relationship between human leukocyte antigen-G (HLA-G), which is involved in immune regulation, and AR in transplant patients. Moreover, 14-bp insertion/deletion polymorphism in the 3' untranslated region (UTR) region of the HLA-G gene is known to affect HLA-G expression. However, its relationship to AR is still controversial. The aim of this study was to investigate whether HLA-G 14-bp insertion/deletion polymorphism contributed to the development of AR in kidney transplant patients using a meta-analysis. Materials and Methods: To perform our meta-analysis, eligible studies about HLA-G 14-bp insertion/deletion polymorphism and AR were searched in electronic databases until 1 June 2021. Finally, a total of 336 patients with AR and 952 patients without AR in relation to kidney transplantation were analyzed from a total of nine studies. Results: In our results, the Del allele and Ins/Del+Del/Del and Del/Del genotypes significantly increased susceptibility of AR in Asian populations [odds ratio (OR) = 2.359, 95% confidence interval (CI) = 1.568-3.550, p = 3.8 × 10-5; OR = 3.357, 95% CI = 1.769-6.370, p = 0.002; OR = 2.750, 95% CI = 1.354-5.587, p = 0.0052 in each model, respectively]. Conclusions: Evidence of the present results indicate that HLA-G 14-bp insertion/deletion polymorphism is associated with susceptibility to AR in the Asian population.

ATP-driven reactions are required for the assembly of large stress granules.

Stress granules (SGs) are functional messenger ribonucleoprotein aggregates, and their assembly is an important cellular process required for remodeling the signaling network to cope with extensive environmental stresses. SG formation is a stepwise process that involves the formation of a stable core followed by a less stable outer shell, and this process is often hampered by faulty regulation of protein phosphorylation. It remains unclear, however, which kinase activity is essential for SG formation. Here, we screened small molecule library of kinase inhibitors using a well-validated fluorogenic SG probe. Our screen, time-lapse microscopy, and biochemical analyses identified an ATP-mimetic SG inhibitor that selectively interferes with the fusion and growth, rather than the initial assembly, of SG core structures into the large assemblies. Thus, SGs utilize ATP-dependent chemical reactions to achieve their functional architectures.

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.

Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

BACKGROUND: Thyroidectomy is the typical treatment for pediatric thyroid carcinoma; total thyroidectomy is commonly performed. We aimed to report our experience at a single tertiary institution and to evaluate the risk factors for recurrence, especially based on surgical extent, in pediatric patients with differentiated thyroid carcinoma (DTC). METHODS: A data of 94 pediatric patients who underwent thyroid surgery for DTC from January 1982 to December 2012 at Yonsei University Hospital (Seoul, Korea) were reviewed. The clinicopathologic features and surgical outcomes were retrospectively analyzed through complete chart reviews. RESULTS: The mean age was 16.6 ± 3.0 (range, 5-19) years. Fourteen patients had recurrence. Tumor size >2 cm (hazard ratio [HR], 14.241; p = 0.011) and positive lymph nodes (HR, 1.056; p = 0.039) were significant risk factors for disease-free survival (DFS) in multivariate analysis. In Kaplan-Meier analysis, a statistically significant difference was noted in the DFS according to tumor size 2 cm (p < 0.001). However, the DFS was not significantly different between the bilateral total thyroidectomy (BTT) and less than BTT groups (p = 0.215). CONCLUSIONS: BTT remains the treatment of choice in pediatric patients with DTC. Lobectomy may be considered for patients with limited disease, including those with tumor size <2 cm, no suspicious lymph nodes, intrathyroidal lesion, and no multifocal disease.