RENAL FUNCTION AND PLASMA RENIN ACTIVITY AS POTENTIAL FACTORS CAUSING HYPERKALEMIA IN PATIENTS WITH THYROID CARCINOMA UNDERGOING THYROID HORMONE WITHDRAWAL FOR RADIOACTIVE IODINE THERAPY.

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients. Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state. Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA. Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS. Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K+ = potassium; Na+ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone.

[Two cases of ischemic stroke due to low protein C caused by severe hyperthyroidism].

We reported two patients with acute ischemic stroke who had presented with symptoms of thyroid storm. Case1: A 43-year-old man abruptly developed left hemiparesis caused by the right middle cerebral artery occlusion. Cardiac evaluations revealed atrial fibrillation and left atrial enlargement. He had successful recanalization after reperfusion therapies. Case 2: A 66-year-old woman with severe bilateral middle cerebral artery stenosis presented with right hemiparesis and dysarthria. MRI revealed the acute infarction in the left frontal and parietal lobe. In both cases, protein C activity was decreased which could be related to severe hyperthyroidism. They concomitantly had arterial lesions where blood stasis could occur. Severe hyperthyroidism which could evoke the decreasing of protein C activity could be responsible to develop acute ischemic stroke.

Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component.

Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.

Regulating size of silver nanoparticles on calcium carbonate via ultrasonic spray for effective antibacterial efficacy and sustained release.

Calcium carbonate is used as bone-filling material due to its good biocompatibility, bioactivity, and bioabsorbability, but the prevalence of infectious complications associated with calcium carbonate has created a persisting challenge in the treatment of bone defect. Therefore, this greatly necessitate the need to endow calcium carbonate with antibacterial properties. In this study, calcium carbonate powders loaded with silver nanoparticles (Ag-CaCO3) were prepared in attempt to serve as a novel antibacterial inorganic filler material. This objective was achieved using ultrasonic spray-pyrolysis (USSP) route to produce Ag-CaCO3 with 1, 5 and 10 mol% silver. The size of silver nanoparticles on CaCO3 microspheres could be regulated by adjusting silver concentration to facilitate effective release of Ag+ ions. This was demonstrated in Ag-CaCO3 (1), where the lowest silver content at 1 mol% achieved the highest Ag+ ions release over 28 days. This in turn gave rise to effective antibacterial efficiency against Staphylococcus aureus and Escherichia coli. Furthermore, CaCO3 (1) could also support osteoblast-like cells (MG-63) at a cell viability of 80%. Overall, this work extends the capabilities in employing USSP to produce inorganic filler materials with sustained antibacterial properties, bringing one step closer to the development of antibacterial products.

Cross-sectional observational study exploring clinical risk of titanium allergy caused by dental implants.

PURPOSE: Studies have reported cases of metal allergy caused by titanium-containing materials. We wished to clarify the relationship between titanium allergy and dental implants by describing patients who suffered allergic symptoms after they had received such implants. METHODS: A total of 270 patients who visited a Dental Metal Allergy Clinic at Tokushima University Hospital from April 2010 to March 2014 were the study cohort. Patch testing with 28 types of metal allergens (including four titanium allergens) was undertaken for patients. RESULTS: A total of 217 patients (80.4 %) exhibited allergy-positive reactions to at least one type of metal allergen. Mercury, palladium, chromium and nickel exhibited a higher prevalence of allergy-positive reactions than other metals. Sixteen patients visited our clinic suffering allergic symptoms after receiving dental implants. Eleven of those patients exhibited allergy-positive reactions for any of the metal allergens, and 4 of these patients had allergy-positive reactions against titanium allergens. The total number of allergy-positive reactions for titanium allergens among all 270 patients was 17 (6.3 %). No patient exhibited a positive reaction only for the titanium allergen. CONCLUSIONS: The prevalence of allergy-positive reactions for titanium allergens was lower than for other metal allergens. We suggest examination of pre-implant patients who have a history of hypersensitivity reactions to metals.

Comparison between flipped classroom and team-based learning in fixed prosthodontic education.

PURPOSE: We previously investigated the effects of team-based learning (TBL) on fixed prosthodontic education and reported that TBL could have higher efficiency with high student satisfaction than traditional lecture. In the current report, we introduced flipped classroom to the fixed prosthodontic education and compared their effectiveness based on the final examination score in addition to TBL. METHODS: Participants were 41 students from Tokushima University School of Dentistry who attended a fixed prosthodontics course. The first six classes adopted the flipped classroom style while the latter eight classes adopted TBL. To evaluate the relationship between learning styles and their effectiveness, we compared results from the term-end examination between the curriculum covered by flipped classroom and TBL-style classes. To draw comparisons, a referential examination with the same questions was conducted to eight faculty members who had not attended any of these classes. RESULTS: Term-end examination results showed that TBL classes had slightly higher scores than flipped classroom classes. Referential examination results also showed higher scores for the same curriculum and no significant interaction was found between class formats and the term-end and referential examination scores. Analysis revealed no noticeable difference in the effectiveness of the class formats. CONCLUSION: Our previous study reported that TBL had higher efficiency than traditional style lecture. In the current study, there was no statistical difference in the examination score between flipped classroom and TBL. Therefore, we conclude that both styles are highly effective than traditional style lecture and constitute valid formats for clinical dental education.

Validity of Peer Evaluation for Team-Based Learning in a Dental School in Japan.

The aim of this study was to determine the validity of peer evaluation for team-based learning (TBL) classes in dental education in comparison with the term-end examination records and TBL class scores. Examination and TBL class records of 256 third- and fourth-year dental students in six fixed prosthodontics courses from 2013 to 2015 in one dental school in Japan were investigated. Results of the term-end examination during those courses, individual readiness assurance test (IRAT), group readiness assurance test (GRAT), group assignment projects (GAP), and peer evaluation of group members in TBL classes were collected. Significant positive correlations were found between all combinations of peer evaluation, IRAT, and term-end examination. Individual scores also showed a positive correlation with group score (total of GRAT and GAP). From the investigation of the correlations in the six courses, significant positive correlations between peer evaluation and individual score were found in four of the six courses. In this study, peer evaluation seemed to be a valid index for learning performance in TBL classes. To verify the effectiveness of peer evaluation, all students have to realize the significance of scoring the team member's performance. Clear criteria and detailed instruction for appropriate evaluation are also required.

Effects of team-based learning on fixed prosthodontic education in a Japanese School of Dentistry.

The aims of this study were to evaluate the quality of team-based learning (TBL) in prosthodontics education for fourth-year dental students at Tokushima University School of Dentistry and to compare this teaching method with traditional lecture-based delivery. Participants in the study were 36 students (22 males and 14 females) who attended the TBL-style fixed prosthodontics course. Ten 60-minute classes were held. The first three were traditional lecture-style classes and were followed by one class introducing the TBL style. The remaining six classes constituted the TBL-format fixed prosthodontics course. The effectiveness of TBL was evaluated through student questionnaires at the end of each class and the results of the term-end examination. The questionnaire revealed high student approval for TBL-style learning, and active group discussion among students during TBL was a key factor in these ratings. In the results of the term-end examination, there were significantly higher scores on the questions that covered TBL-taught material than those covering traditional lecture-taught topics. The results of this study suggest that TBL-style lecture was more effective than traditional-style lecture for teaching fixed prosthodontics and that TBL was a more efficient mode of delivering dental education than traditional lecture-based teaching.

A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells.

INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in inducing a cascade of reactions toward tissue regeneration or reparative dentin formation or both. Previous reports have shown that inflammatory cytokines regulate the differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none has interrogated the impact of these cytokines on the stem cell phenotype of stem/progenitor cells. This study investigated the effects of a short-term treatment with TNF-α on the stem cell phenotype and differentiation ability of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during the initial stage of inflammatory response. For in vitro studies, human DPCs were isolated and incubated with TNF-α for 2 days and passaged to eliminate TNF-α completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell migration, colony-forming ability, and differentiation toward odontogenesis and adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a strong staining for CD146 during the initial inflammatory response, at 2 days after pulp exposure. In vitro experiments demonstrated that a short-term (2-day) treatment of TNF-α increased by twofold the percentage of SSEA-4+ cells. Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG mRNA levels were also significantly upregulated upon TNF-α treatment. A short-term TNF-α treatment also enhanced DPC function, including the ability to form cell colonies, to migrate, and to differentiate into odontogenic and adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-α enhanced the stem cell phenotype, migration, and differentiation ability of DPCs.