Radiopharmaceuticals for Skeletal Muscle PET Imaging.

The skeletal muscles account for approximately 40% of the body weight and are crucial in movement, nutrient absorption, and energy metabolism. Muscle loss and decline in function cause a decrease in the quality of life of patients and the elderly, leading to complications that require early diagnosis. Positron emission tomography/computed tomography (PET/CT) offers non-invasive, high-resolution visualization of tissues. It has emerged as a promising alternative to invasive diagnostic methods and is attracting attention as a tool for assessing muscle function and imaging muscle diseases. Effective imaging of muscle function and pathology relies on appropriate radiopharmaceuticals that target key aspects of muscle metabolism, such as glucose uptake, adenosine triphosphate (ATP) production, and the oxidation of fat and carbohydrates. In this review, we describe how [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), [18F]fluorocholine ([18F]FCH), [11C]acetate, and [15O]water ([15O]H2O) are suitable radiopharmaceuticals for diagnostic imaging of skeletal muscles.

A novel chalcone derivative exerts anticancer effects by promoting apoptotic cell death of human pancreatic cancer cells.

Aggressive pancreatic cancer is typically treated using chemotherapeutics to reduce the tumor pre-operatively and prevent metastasis post-operatively, as well as surgical approaches. In the present study, we synthesized a hydroxyl group-introduced chalcone derivative (1, IC50 = 32.1 µM) and investigated its potential as an anticancer drug candidate by evaluating its apoptosis-promoting effects on BXPC-3 cancer cells. The viability of BXPC-3 cells treated with 1 was measured using the water-soluble tetrazolium 1 reagent. BXPC-3 cells induced by 1 were stained with diverse probes or antibodies, such as ethidium homodimer-1, Hoechst, anti-Ki67, and MitoTracker. Protein expression was measured using an immunoblotting assay, and mRNA expression was determined using real-time polymerase chain reaction. Apoptotic molecular features, such as lipid accumulation and protein degradation, were monitored directly using stimulated Raman scattering microspectroscopy. Through incubation time- and concentration-dependent studies of 1, we found that it significantly reduced the proliferation and increased the number of apoptotic BXPC-3 cells. Compound 1 induced mitochondrial dysfunction, phosphorylation of p38, and caspase 3 cleavage. These results indicate that 1 is a potential therapeutic agent for pancreatic cancer, providing valuable insights into the development of new anticancer drug candidates.

Using acellular porcine dermal matrix (XCM Biologic® Tissue Matrix) to repair a giant omphalocele: A case report.

RATIONALE: An omphalocele is an abdominal wall birth defect, and a giant omphalocele (GO) is defined as an omphalocele having a diameter >5 cm or containing a herniated liver. GOs are usually treated in stages and in this case, during the silo reduction, dehiscence occurred at the suture site of the axis ring and skin edge, which was repaired using synthetic absorbable mesh. PATIENT CONCERNS: A girl infant was born at 36 weeks with a GO of 8 cm diameter, and herniated multiple organs such as the small bowel, cecum, appendix, and the entire liver. Even after the staged repair technique for the GO silo, wound dehiscence between the ring of the silo and the edge of the skin occurred and gradual reduction failed. DIAGNOSIS: A GO of 8 cm diameter, which was found during prenatal ultrasonography. INTERVENTIONS: Revision was performed to repair the defect. The small bowel and liver were still prolapsed, and there were severe adhesions. After adhesiolysis, the muscle layer of the abdominal wall was repaired using the tissue matrix, but the skin could not be repaired. After the second operation, the defect wound was dressed as sterilely as possible. OUTCOMES: The abdominal wall defect was repaired completely; there were no residual complications. LESSONS: Repair of GOs using an acellular porcine dermal matrix can be considered a viable treatment option.

Tannic acid-functionalized boron nitride nanosheets for theranostics.

Here, we report a tannic acid-Fe3+ coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.e., dopamine, 3,4-dihydroxyphenylacetic acid, gallic acid, and tannic acid), a coating of tannic acid-Fe3+ coordination complex provided the highest magnetic field relaxivity and near infrared (NIR) laser light responsiveness. An in vitro study showed that KB tumor cells treated with tannic acid-Fe3+ coordination complex adsorbed on BNS (TA-Fe/BNS) exhibited higher T1-weighted magnetic resonance contrast compared with plain BNS, and BNS coated with tannic acid or Fe alone. NIR irradiation at 808 nm caused a significant increase in KB tumor cell death after treatment with TA-Fe/BNS compared with other treatments. In vivo MRI imaging revealed tumor accumulation of intravenously administered TA-Fe/BNS. Guided by MRI information, application of focused laser irradiation onto tumor tissues resulted in complete tumor ablation. These results support the potential of TA-Fe/BNS for MRI theranostics. Moreover, this study suggests the wide applicability of TA-Fe noncovalent coating as biocompatible and facile tool for converting nonfunctional early-generation nanomaterials into functional new nanomaterials, opening new opportunities for their use in translational biomedical applications such as MRI theranostics.

Pentraxin-3 Modulates Osteogenic/Odontogenic Differentiation and Migration of Human Dental Pulp Stem Cells.

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

A Microbial Siderophore-Inspired Self-Gelling Hydrogel for Noninvasive Anticancer Phototherapy.

Microbial carboxyl and catechol siderophores have been shown to have natural iron-chelating abilities, suggesting that hyaluronic acid (HA) and the catechol compound, gallic acid (GA), may have iron-coordinating activities. Here, a photoresponsive self-gelling hydrogel that was both injectable and could be applied to the skin was developed on the basis of the abilities of HA and GA to form coordination bonds with ferric ions (Fe3+). The conjugate of HA and GA (HA-GA) instantly formed hydrogels in the presence of ferric ions and showed near-infrared (NIR)-responsive photothermal properties. Following their subcutaneous injection into mice, HA-GA and ferric ion formed a hydrogel, which remained at the injection site for at least 8 days. Intratumoral injection of HA-GA/Fe hydrogel into mice allowed repeated exposure of the tumor to NIR irradiation. This repeated NIR irradiation resulted in complete tumor ablation in KB carcinoma cell-xenografted mice and suppressed lung metastasis of 4T1-Luc orthotopic breast tumors. Application of HA-GA/Fe hydrogel to the skin of A375 melanoma-xenografted tumor sites, followed by NIR irradiation, also resulted in complete tumor ablation. These findings demonstrate that single applications of HA-GA/Fe hydrogel have photothermal anticancer effects against both solid tumors and skin cancers. SIGNIFICANCE: These findings provide new insights into noninvasive anticancer phototherapy using self-gelling hydrogels. Application of these hydrogels in preclinical models reduces the sizes of solid tumors and skin cancers without surgery, radiation, or chemotherapy.

Association between internet gaming addiction and leukocyte telomere length in Korean male adolescents.

Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth. In particular, the potential association between IGA and leukocyte telomere length (LTL) has yet to be examined. In this study we compared LTL in Korean male adolescents with and without IGA and examined the association between LTL and autonomic functions. Specifically, plasma catecholamine, serum cortisol, and psychological stress levels were measured as autonomic functions. Data were collected using participant blood samples analyzed for LTL, catecholamine, and cortisol levels and a set of questionnaires to assess IGA and psychological stress levels of the participants. The LTL measurements were made using a qPCR-based technique, and the relative LTL was calculated as the telomere/single copy (T/S) ratio. T/S ratio was significantly shorter in the IGA group than in the non-IGA group (150.43 ±â€¯6.20 and 187.23 ±â€¯6.42, respectively; p < .001) after adjusting for age. In a univariate regression analysis, age, daily Internet gaming time, IGA score, and catecholamine level (epinephrine and norepinephrine) were significantly associated with T/S ratio. However, duration of Internet gaming exposure, dopamine, cortisol, and psychological stress levels were not found to be associated with T/S ratio. In the final multiple linear regression model, age, daily Internet gaming time, and epinephrine level showed statistically significant relationships with T/S ratio. Our results indicate that in addition to age, involvement in excessive Internet gaming may induce LTL shortening in male adolescents, which may be partially attributable to changes in autonomic function such as catecholamine level. These findings further understanding of the health effects of IGA and highlight the need for screening and intervention strategies for male adolescents with IGA.

Nanoformulation-based sequential combination cancer therapy.

Although combining two or more treatments is regarded as an indispensable approach for effectively treating cancer, the traditional cocktail-based combination therapies are seriously limited by coordination issues that fail to account for differences in the pharmacokinetics and action sites of each drug. The careful manipulation of dosing regimens, such as by the sequential application of combination treatments, may satisfy the temporal and spatial needs of each drug and achieve successful combination antitumor therapy. Nanotechnology-based carriers might be the best tools for sequential combination therapy, as they can be loaded with multiple cargos and may provide targeted and sustained delivery to target tumor cells. Single nanoformulations capable of sequentially releasing drugs have shown synergistic anticancer activity, such as by sensitizing tumor cells through cascaded drug delivery or remodeling the tumor vasculature and microenvironment to enhance the tumor distribution of nanotherapeutics. This review highlights the use of nanotechnology-based multistage drug delivery for cancer treatment, focusing on the ability of such formulations to enhance antitumor efficacy by applying sequential treatment and modulating dosing regimens, which are challenges currently being faced in the clinic.

Graphene-based nanosheets for delivery of chemotherapeutics and biological drugs.

Graphene-based nanosheets (GNS), including graphenes, graphene oxides and reduced graphene oxides, have properties suitable for delivery of various molecules. With their two-dimensional structures, GNS provide relatively high surface areas and capacity for non-covalent π-π stacking and hydrophobic interactions with various drug molecules. Currently, GNS-based delivery applications extend to chemotherapeutics as well as biological drugs, including nucleic acid drugs, proteins, and peptides. Surfaces of GNS have been modified with various polymers, such as polyethylene glycol and biopolymers, which enhance biocompatibility and increase drug loading. Anticancer drugs are prominent among chemotherapeutic agents tested, and have been loaded onto GNS with relatively high loading capacities compared with other nanocarriers. For enhanced distribution to specific tissues, GNS have been covalently or non-covalently modified with targeting ligands, including folic acid, transferrins, and others. In this review, we cover the current status of GNS for delivery of anticancer chemotherapeutics and biological drugs, with a focus on nucleic acid drugs. Remaining challenges for the application of GNS for drug-delivery systems and future perspectives are also addressed.

Single-Tooth Implant Versus Three-Unit Fixed Partial Denture: A Study of Oral Health-Related Quality of Life.

PURPOSE: Many studies have investigated the impact of prosthetic treatment on oral health-related quality of life (OHRQoL). However, most of these have been performed among fully or partially edentulous patients. Studies involving patients with a single missing tooth are limited. The purpose of this study was to compare the OHRQoL between patients treated by single-tooth implants and three-unit fixed partial dentures (FPDs) for single missing tooth restoration. MATERIALS AND METHODS: A cross-sectional survey was conducted in Korea with patients drawn by stratified purposive sampling based on age. OHRQoL was measured using the Korean version of the 14-item Oral Health Impact Profile (OHIP-14K) questionnaire. Pre- and posttreatment OHIP-14K scores were compared by paired t test. Single-tooth implants and three-unit FPDs were compared by two-sample t test. In addition, multiple regression analysis was used to evaluate the impact of treatment mode on OHIP-14K total score after adjusting the effect of demographics and clinical factors. RESULTS: Thirty-five patients with single-tooth implants and 36 patients with three-unit FPDs were included. All participants had a significant improvement in OHRQoL compared with before the treatment (P < .0001). However, there was no statistically significant difference in the change of OHIP-14K score between the two treatment modes. In addition, the treatment mode had no significant impact on the change of OHIP-14K total score after adjusting the influence of covariates (P = .170). CONCLUSION: Both single-tooth implants and three-unit FPDs for single missing tooth replacement resulted in significant and similar improvement of OHRQoL.

Comparison of fixed implant-supported prostheses, removable implant-supported prostheses, and complete dentures: patient satisfaction and oral health-related quality of life.

OBJECTIVES: The purpose of this study was to compare patient satisfaction and oral health-related quality of life (OHRQoL) among fully edentulous patients treated with either fixed implant-supported prostheses (FP), removable implant-supported prostheses (RP), or complete dentures (CD). MATERIAL AND METHODS: Eighty-six patients - 29 FP, 27 RP, and 30 CD patients - participated in this study. The survey was conducted using face-to-face interviews with a questionnaire that included a patient satisfaction scale and Oral Health Impact Profile (OHIP-14). We measured patient satisfaction after prosthetic treatments and OHRQoL before and after the treatments. RESULTS: After prosthetic treatments, OHRQoL increased in all three groups (P < 0.05). The FP and RP groups showed no significant difference in patient satisfaction and OHRQoL, and both groups showed greater improvement compared with the CD group. Specifically, the OHRQoL dimensions of functional limitation, physical pain, psychological discomfort, and psychological disability in the FP group, and functional limitation in the RP group, improved greatly in comparison with the CD group (P < 0.05). CONCLUSIONS: Although further research is still needed, prosthetic treatments may provide superior OHRQoL for fully edentulous patients. In particular, both the FP and RP treatments provided significantly greater improvement of OHRQoL and patient satisfaction than the CD treatment. Reliable information of OHRQoL and patient satisfaction helps experts and patients choose the best prosthetic treatment option.

Biomimetic DNA nanoballs for oligonucleotide delivery.

Here, we designed biomimetic DNA nanoballs for delivery of multiple antisense oligonucleotides (ASOs). DNA templates with ASOs-complementary sequences were amplified by rolling circle amplification (RCA). RCA products were loaded with two types of ASOs by hybridization, condensed using adenovirus-derived Mu peptide, and coated with hyaluronic acid (HA) for delivery into CD44-overexpressing tumor cells. HA-coated, Mu peptide-condensed, dual ASO-loaded DNA nanoballs (HMA nanoballs) showed considerable cellular entry of Cy5-incorporated RCA product DNA and fluorescent ASOs, whereas Mu peptide-condensed, dual ASO-loaded DNA nanoballs (MA nanoballs) revealed limited uptake. Dual ASOs, Dz13 and OGX-427, delivered by HMA nanoballs could reduce the levels of protein targets and exert anticancer effects. Enhanced tumor distribution was observed for fluorescent HMA nanoballs than the corresponding MA nanoballs. Upon intravenous co-administration with doxorubicin, HMA nanoballs exerted the greatest anti-tumor effects among the groups. These results suggest HMA nanoballs as a nanoplatform for sequence-specific delivery of multiple ASOs and other functional oligonucleotides.

Polyaptamer DNA nanothread-anchored, reduced graphene oxide nanosheets for targeted delivery.

Here, we report reduced graphene oxide (rGO) nanosheets anchoring receptor-specific polyaptamer nanothreads for targeted drug delivery. DNA polyaptamer nanothreads of protein tyrosine kinase 7 receptor (PTK7) were synthesized by rolling cycle amplification. To strengthen the anchoring of polyaptamer nanothreads onto rGO, oligoT bridge domain was introduced between each repeating PTK7 aptamer sequence. As compared to PTK7 polyaptamer nanothreads alone, PTK7 polyaptamer nanothreads with 22-mer oligoT bridges (PNT) showed higher anchoring capacity onto rGO nanosheets. Nanothread-coated surface morphology of PNTrGO was observed. Coating of PNT did not affect the sizes of rGO, but reduced the zeta potential. In PTK7-negative Ramos cells, the uptake of PNT-anchored rGO (PNTrGO) did not differ from that of oligoT-bridged scrambled polyaptamer-anchored rGO (SNTrGO). However, in CCRF-CEM leukemia cells overexpressing PTK7, the uptake of PNTrGO was 2.1-fold higher than that of SNTrGO after 15 min pulse. In vivo distribution to CCRF-CEM tumor tissues was 2.8-fold higher in PNTrGO than in SNTrGO at 48 h post-injection. In CCRF-CEM xenografted mice, intravenously administered doxorubicin (Dox)-loaded PNTrGO showed the higher antitumor activity than other groups, reducing the tumor weight down to 12% of tumor weights of untreated mice. These results suggest the potential of PNTrGO for target-specific drug delivery nanoplatform.

Economic evaluation of single-tooth replacement: dental implant versus fixed partial denture.

PURPOSE: This study assessed the cost-effectiveness from a societal perspective of a dental implant compared with a three-unit tooth-supported fixed partial denture (FPD) for the replacement of a single tooth in 2010. MATERIALS AND METHODS: A decision tree was developed to estimate cost-effectiveness over a 10-year period. The survival rates of single-tooth implants and FPDs were extracted from a meta-analysis of single-arm studies. Medical costs included initial treatment costs, maintenance costs, and costs to treat complications. Patient surveys were used to obtain the costs of the initial single-tooth implant or FPD. Maintenance costs and costs to treat complications were based on surveys of seven clinical experts at dental clinics or hospitals. Transportation costs were calculated based on the number of visits for implant or FPD treatment. Patient time costs were estimated using the number of visits and time required, hourly wage, and employment rate. Future costs were discounted by 5% to convert to present values. RESULTS: The results of a 10-year period model showed that a single dental implant cost US $261 (clinic) to $342 (hospital) more than an FPD and had an average survival rate that was 10.4% higher. The incremental cost-effectiveness ratio was $2,514 in a clinic and $3,290 in a hospital for a prosthesis in situ for 10 years. The sensitivity analysis showed that initial treatment costs and survival rate influenced the cost-effectiveness. If the cost of an implant were reduced to 80% of the current cost, the implant would become the dominant intervention. CONCLUSION: Although the level of evidence for effectiveness is low, and some aspects of single-tooth implants or FPDs, such as satisfaction, were not considered, this study will help patients requiring single-tooth replacement to choose the best treatment option.

Estimating the burden of irritable bowel syndrome: analysis of a nationwide korean database.

BACKGROUND/AIMS: Management of irritable bowel syndrome (IBS) imposes a heavy economic burden. This study was to estimate the epidemio-logic features of IBS and to report the IBS burden for the first time in the Korean population. METHODS: A cross-sectional study was conducted using the National Health Insurance (NHI) system database, which covers the entire pop-ulation of Korea. IBS was defined as diagnostic code -10 in adults with any outpatient clinic visits or hospitalization related to IBS. We excluded diseases that mimic IBS symptoms. RESULTS: A total of 2.42 million (58.2% female) individuals were identified as patients with IBS, yielding an age- and gender-adjusted prevalence of 5.1% in males and 6.9% in females. The prevalence of IBS increased proportionally with age, with higher medical costs in middle-aged patients. Outpatient clinics were visited by 98.6% of IBS patients, and 1.9% were treated upon admission. Of these patients, 87.6% were given a prescription. Co-morbidities that commonly accompanied IBS included upper gastro-intestinal (36.1%), respiratory (12.3%), musculoskeletal (8.0%) disease, somatoform (4.3%) and depression/anxiety disorders (3.1%). The NHI costs of IBS, which include the NHI covered cost and beneficiary copayment charges, were estimated to be 155 million USD, which accounts for 0.46% of the total NHI costs for the entire Korean population. CONCLUSIONS: According to the Korean national claims database, about 6% of the Korean population seeks medical care for IBS at least once per year. This high prevalence places a large economic burden on the Korean healthcare system, accounting for 0.46% of over-all national medical expenditure.

Enhanced survival of transplanted human adipose-derived stem cells by co-delivery with liposomal apoptosome inhibitor in fibrin gel matrix.

To improve the survival of transplanted human adipose-derived stem cells (ADSCs), a liposome preparation containing the apoptosome inhibitor, NS3694, was formulated and co-delivered with ADSCs in fibrin gel scaffolds. Liposomes provided enhanced effect on ADSC proliferation in vitro as compared to free drug. Exposure of ADSCs to liposomal NS3694 for 7 days did not affect the surface marker expression profile. NS3694 encapsulated in negatively charged liposomes composed of phosphatidylcholine, phosphatidylglycerol, and cholesterol was evaluated in vivo following subcutaneous transplantation in mice. Survival of ADSCs co-delivered with liposomal NS3694 was significantly higher than that of untreated ADSCs or ADSCs treated with free NS3694 or empty liposomes. An immunohistochemical analysis revealed a higher number of human nucleus-positive cells after treatment with liposomal NS3694 than following treatment with free NS3694. Similarly, liposomal NS3694 significantly enhanced survival of transplanted ADSCs in rabbits compared to other treatments. Taken together, our results indicate the potential of liposomal NS3694 co-delivered with ADSCs using fibrin gel systems as an in vivo-survival enhancer.

Percutaneous osteoplasty for the treatment of a painful osteochondral lesion of the talus: a case report and literature review.

An osteochondral lesion of the talus (OLT) is a lesion involving the talar articular cartilage and its subchondral bone. OLT is a known cause of chronic ankle pain after ankle sprains in the active population. The lesion causes deep ankle pain associated with weight-bearing, impaired function, limited range of motion, stiffness, catching, locking, and swelling. There are 2 common patterns of OLTs. Anterolateral talar dome lesions result from inversion and dorsiflexion injuries of the ankle at the area impacting against the fibula. Posteromedial lesions result from inversion, plantar flexion, and external rotation injuries of the ankle at the area impacting against the tibial ceiling of the ankle joint. Early diagnosis of an OLT is particularly important because the tibiotalar joint is exposed to more compressive load per unit area than any other joint in the body. Failure of diagnosis can lead to the evolution of a small, stable lesion into a larger lesion or an unstable fragment, which can result in chronic pain, joint instability, and premature osteoarthritis. A 43-year-old man, with a history of ankle sprain one year previously, visited our pain clinic for continuous right ankle pain after walking or standing for more than 30 minutes. There was a focal tenderness on the posteromedial area of the right talus. Imaging studies revealed a posteromedial OLT classified as having a geode form according to the FOG (fractures, osteonecroses, geodes) radiological classification and categorized as a stage 2a lesion on magnetic resonance imaging. The patient was scheduled for aspiration and osteoplasty with hydroxyapatite under arthroscopic and fluoroscopic guidance. A 26-gauge needle was inserted to infiltrate local anesthetics into the skin over the cyst and ankle joint. An arthroscope was placed into the joint to approach the OLT. The arthroscopic view showed that there was no connection between the OLT and the cyst of the talus body. A 13-gauge bone biopsy needle was inserted into the cyst, and aspiration was performed. Aspirated fluid from the cyst was originally white and clear; however, it changed to a blood-tinged, reddish color due to mixing with the incisional blood. After aspiration, contrast medium was injected, and the shape of the spread was observed. Bone cement comprising hydroxyapatite was injected to fill the bone defect of the cyst. A 1.5 mL volume of cement was injected into the talus under vigilant fluoroscopic and arthroscopic monitoring to prevent its dissemination into the joint. There was no cement leakage into the vessels or articular space. Postoperative fluoroscopy and computed tomography images showed bone cement filling of the defect. In the present case, arthroscopic and fluoroscopic guidance was used for aspiration of an OLT and for performing percutaneous osteoplasty with hydroxyapatite for one defect; this treatment decreased pain upon weight bearing and enabled a return to work without any restrictions one week after the procedure. The purpose of this report was to highlight the presence of OLT in chronic ankle pain and to review its management strategies.

Hypothermic cardiopulmonary bypass for minimally invasive mitral valve plasty in adult moyamoya disease.

A 43-year-old man underwent minimally invasive mitral valve plasty of a flail mitral valve. Four years previously, he had been diagnosed with moyamoya disease (MMD) by cerebral magnetic resonance imaging/angiography findings. In MMD, risk factors for cerebral stroke include changes in arterial carbon dioxide partial pressure, blood pressure, and body temperature. And during cardiopulmonary bypass (CPB), these hemodynamic changes can be challenging. However, hypothermia during CPB can decrease cerebral oxygen consumption and have a cerebral protective effect. We performed a minimally invasive mitral valve plasty, using hypothermic CPB, in a patient with MMD, without any neurological deficits.

Preoperative BRAF mutation has different predictive values for lymph node metastasis according to tumor size.

OBJECTIVE: To investigate whether BRAF mutation of papillary thyroid carcinoma (PTC) has different predictive values for regional lymph node (LN) metastasis according to tumor size. STUDY DESIGN: Prospective cohort study. Setting. A tertiary hospital. SUBJECTS AND METHODS: From January 2009 to August 2009, the authors prospectively enrolled 102 consecutive patients with unifocal PTC based on the findings of ultrasonography-guided fine-needle aspiration biopsy (FNAB). BRAF mutation was tested on preoperative FNAB specimens. Total thyroidectomy and bilateral central neck dissection (± lateral neck dissection) was performed for all patients. Among 102 patients, 71 who were confirmed to have unifocal PTC by the surgical pathology were finally selected. The 71 patients were classified into 3 groups according to their tumor size: group I, ≤0.5 cm; group II, >0.5 cm and ≤1 cm; and group III, >1 cm. LN metastasis was evaluated in the surgical specimen as a dependent variable. The authors investigated whether BRAF mutation is predictive of LN metastasis in each group. RESULTS: Overall, BRAF mutation was a significant predictor of LN metastasis (P = .045). When patients were classified into 3 groups, frequency of LN metastasis increased with tumor size: 4.8%, 50.0%, and 66.7% (P < .001). However, the frequency of BRAF mutation was not different among 3 groups: 61.9%, 56.3%, and 72.2% (P = .536). BRAF mutation was predictive of LN metastasis only in group II (P = .026). CONCLUSION: BRAF mutation of PTC may have differential predictive values for LN metastasis, according to tumor size.

Topical administration of cyclosporin A in a solid lipid nanoparticle formulation.

Cyclosporin A (CsA)-loaded solid lipid nanoparticles (SLN) were developed for improved skin penetration. CsA-loaded SLN, prepared using a hot homogenization method, were nano-sized (about 73 nm) with a slightly negative surface charge (about -16 mV) and stable under physiological conditions regardless of CsA incorporation. In vitro permeation studies using murine skin mounted in the Franz-type vertical diffusion assembly revealed that the skin permeation efficiency of CsA-loaded SLN was 2-fold higher than that of CsA-oil mixture in viable skin. Furthermore, topically administered CsA-loaded SLN relieved symptoms of atopic dermatitis (AD) in an in vivo murine model of AD by decreasing the T helper (Th) 2 cell-related cytokines interleukin (IL)-4 and -5. These results suggest that SLN are effective drug carriers for topical delivery andthat CsA-loaded SLN can be therapeutically applied in allergy-related skin disorders.