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IntroductionAlthough active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy.MethodsSerum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery.ResultsSerum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant.Conclusion1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Abstract This paper explores the evolutional process of back-arc basin (BAB) magma system at final spreading stage of extinct BAB, Shikoku Basin (Philippine Sea) and assesses its tectonic evolution using a newly discovered oceanic core complex, the Mado Megamullion. Bulk and in-situ chemical compositions together with in-situ Pb isotope composition of dolerite, oxide gabbro, gabbro, olivine gabbro, dunite, and peridotite are presented. Compositional ranges and trends of the igneous and peridotitic rocks from the Mado Megamullion are similar to those from the slow- to ultraslow-spreading mid-ocean ridges (MOR). Since the timing of the Mado Megamullion exhumation corresponds to the very end of the Shikoku Basin opening, the magma supply was subdued and highly episodic, leading to extreme magma differentiation to form ferrobasaltic, hydrous magmas. In-situ Pb isotope composition of magmatic brown amphibole in the oxide gabbro is identical to that of depleted source mantle for mid-ocean ridge basalt (MORB). In the context of hydrous BAB magma genesis, the magmatic water was derived solely from the MORB source mantle. The distance from the back-arc spreading center to the arc front increased away through maturing of the Shikoku Basin to cause MORB-like magmatism. After the exhumation of Mado Megamullion along detachment faults, dolerite dikes intruded as a post-spreading magmatism. The final magmatism along with post-spreading Kinan Seamount Chain volcanism were introduced around the extinct back-arc spreading center after the opening of Shikoku Basin by residual mantle upwelling.

Abstract Background Adult-onset Still’s disease (AOSD) is a self-inflammatory disease showing macrophage and neutrophil activation by inflammatory cytokines such as TNF-α, IL-6, and IL-18. Although some cases with the flare of AOSD during pregnancy have been reported, most had flares in the first or second trimester and few had flares in the third trimester. In this report, we present the case of a patient with recurrent flare of AOSD in the third trimester and discuss the management of AOSD in the third trimester with the review of previous literatures. Case presentation A 38-year-old woman in complete AOSD remission without medication presented with impaired liver function, low platelet count, mild fever, abdominal pain, splenomegaly, and elevated ferritin and IL-18 levels at 30 gestational weeks. Although the laboratory data and physical examination finding suggested HELLP syndrome or acute fatty liver of pregnancy and we considered the termination of her pregnancy, her fetus was in a reactive status. Considering her fetal status, some specific findings of AOSD, and her AOSD history, we and rheumatologists diagnosed her with AOSD recurrence and started systemic steroid therapy. In her clinical course, three flares of AOSD occurred, twice in the third trimester and once in postpartum; twice systemic steroid pulse therapies were then needed. Ultimately, a healthy infant was delivered transvaginally at 36 gestational weeks spontaneously. Conclusions Specific findings of the flare of AOSD such as fever, splenomegaly, elevated ferritin and IL-18 levels, and fetal status could be useful findings for differentiation from HELLP syndrome and AFLP in the third trimester. With the careful management supported by rheumatologists, patients complicated with the flare of AOSD may continue their pregnancy longer than we expected.

Abstract On June 29, 2015, a small phreatic eruption occurred in the most intensively steaming area of Hakone volcano, Japan. A previous magnetotelluric survey for the whole volcano revealed that the eruption center area (ECA) was located near the apex of a bell-shaped conductive body (resistivity

Nodal metastasis is crucial for determining the stage of well-differentiated thyroid cancer (WTC) in patients older than 55. Well-formed thyroid follicular inclusions (TFIs) are occasionally encountered in the cervical lymph nodes (LNs) of patients with papillary thyroid carcinoma (PTC), and it is difficult to determine whether they are true nodal metastases or ectopic thyroid tissues (ETT). This study aimed to elucidate the impact of the expression of the DNA damage response molecule TP53-binding protein 1 (53BP1) using immunofluorescence (IF) as a biomarker to differentiate TFIs in cervical LN by comparing the mutation analyses of primary thyroid cancers. The data demonstrated the necessity for the differential diagnosis of true metastases from ETT among TFIs in cervical LNs. PTC-like nuclear features using hematoxylin–eosin staining combined with immunohistochemistry for conventional biomarkers of PTC, including BRAFV600E protein, were most helpful in identifying metastatic follicular-patterned carcinomas. In conclusion, IF analysis of 53BP1 expression could be an excellent ancillary technique to distinguish metastatic carcinoma or ETT from TFIs in LNs, particularly in cases other than BRAFV600E-mutated PTC.

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.

ABSTRACT: Objective: The objective of this report was to describe an unusual case of emerging primary hyperparathyroidism (PHPT) accompanied by recovery of parathyroid blood flow 3 months after spontaneous parathyroid hemorrhage. Methods: Neck images and laboratory tests including serum calcium and parathyroid hormone (PTH) were performed to evaluate parathyroid hemorrhage. Pathologic findings after parathyroidectomy are also presented. Results: A 58-year-old woman developed acute onset of neck pain and swelling with ecchymosis. Computed tomography showed a right paratracheal hematoma-like lesion behind the thyroid. Ultrasound (US) of the neck revealed a round, hypoechoic nodule measuring 27 × 25 × 18 mm in the right lower thyroid pole without vascular flow. Blood tests showed a corrected calcium of 9.3 mg/dL (normal, 8.7 to 10.3 mg/dL), and intact PTH of 68 pg/mL (normal, 10 to 65 pg/mL). Intact PTH measurement in fine-needle aspirate of the lesion was 339 pg/mL, confirming parathyroid origin. Repeat US after 3 months showed a remarkable decrease in lesion size with significant blood flow. Blood biochemistry showed a corrected calcium of 10.9 mg/dL, and an intact PTH of 237 pg/mL. She eventually underwent parathyroidectomy, and pathologic examination revealed parathyroid adenoma with a tiny thrombus. Conclusion: Spontaneous remission of PHPT after parathyroid hemorrhage has been known to occur sporadically, a phenomenon referred to as autoparathyroidectomy. Although spontaneous remission with permanent improvement of PHPT may be observed, PHPT can recur in the relative short term after parathyroid hemorrhage, and so follow-up blood biochemistry surveillance is necessary. Also, evaluating parathyroid blood flow using color Doppler US might be useful in verifying the recurrence of PHPT. Abbreviations: PHPT primary hyperparathyroidism PTH parathyroid hormone US ultrasound

In Japan, fine-needle aspiration (FNA) cytology is the most important diagnostic modality for triaging patients with thyroid nodules. A clinician (endocrinologist, endocrine surgeon, or head and neck surgeon) generally performs FNA cytology at the outpatient clinic, and ultrasound (US)-guided FNA is widespread because US is extremely common and most clinicians are familiar with it. Although almost all FNA thyroid samples are examined by certified cytopathologists and pathologists, some clinicians assess cytological specimens themselves. In Japan, there are two clinical guidelines regarding the management of thyroid nodules. One is the General Rules for the Description of Thyroid Cancer (GRDTC) published by the Japanese Society of Thyroid Surgery (JSTS) in 2005, and the other is the national reporting system for thyroid FNA cytology published by the Japan Thyroid Association in 2013 (Japanese system). Although the Bethesda System for Reporting Thyroid Cytopathology (Bethesda system) is rarely used in Japan, both the GRDTC and Japanese system tried to incorporate the Bethesda system so that the cytological diagnoses would be compatible with each other. The essential point of the Japanese system is stratification of follicular neoplasm (FN) into three subgroups based on cytological features in order to reduce unnecessary diagnostic thyroidectomy, and this system has been successful in stratifying the risk of malignancy in FN patients at several high-volume thyroid surgery centers. In Japan, the measurement of thyroglobulin and/or calcitonin in FNA needle washings is often used as an adjunct for diagnosis of possible cervical lymph node metastasis when FNA cytology is performed.

This study aimed to determine whether additional tissue sampling of encapsulated thyroid nodules would increase the frequency of follicular thyroid carcinoma (FTC) diagnoses. We examined thyroid tissue specimens from 86 patients suspected of FTC (84.9% female; mean age, 49.0 ± 17.8 years). The number of tissue blocks created for pathological assessments ranged from 3 to 20 (mean, 9.1 ± 4.1); the numbers in the previous method recommended by the Japanese General Rules for the Description of Thyroid Cancer and additional blocks ranged from 1 to 12 (mean, 6.0 ± 2.8) and from 1 to 8 (mean, 3.1 ± 2.0), respectively. The additional blocks were subsequently examined to determine whether any diagnoses changed from those based on the previous method. Five patients were diagnosed with FTC using the previous method; however, additional tissue blocks led to the diagnosis of FTC in 6 patients, as 1 diagnosis was revised from follicular adenoma to FTC. It has been reported that increasing the number of tissue blocks used for pathological assessments can increase the frequency of FTC diagnoses; however, this was not clinically significant in thyroid carcinoma, which requires completion thyroidectomy and radioactive iodine treatment. It resulted in no benefits to the patient because all minimally invasive FTCs, follicular tumors of uncertain malignant potential (FT-UMP), and follicular adenomas are treated with lobectomy alone in Japan. Additional tissue sampling only had a slight impact on our thyroid practice; therefore, we decided to cease it.

Apple latent spherical virus (ALSV) was successfully used in promoting flowering (virus-induced flowering, VIF) in apple and pear seedlings. In this paper, we report the use of ALSV vectors for VIF in seedlings and in vitro cultures of grapevine. After adjusting experimental conditions for biolistic inoculation of virus RNA, ALSV efficiently infected not only progeny seedlings of Vitis spp. ‘Koshu,’ but also in vitro cultures of V. vinifera ‘Neo Muscat’ without inducing viral symptoms. The grapevine seedlings and in vitro cultures inoculated with an ALSV vector expressing the ‘florigen’ gene (Arabidopsis Flowering locus T, AtFT) started to set floral buds 20−30 days after inoculation. This VIF technology was successfully used to promote flowering and produce grapes with viable seeds in in vitro cultures of F1 hybrids from crosses between V. ficifolia and V. vinifera and made it possible to analyze the quality of fruits within a year after germination. High-temperature (37 °C) treatment of ALSV-infected grapevine disabled virus movement to newly growing tissue to obtain ALSV-free shoots. Thus, the VIF using ALSV vectors can be used to shorten the generation time of grapevine seedlings and accelerate breeding of grapevines with desired traits.

We report a case of interstitial cystitis (IC) associated with primary Sj ö gren's syndrome (SS) successfully controlled with combination therapy of tacrolimus and a corticosteroid. In 2011, a 69-year-old female, who had been diagnosed with primary SS 23 years ago, developed IC and was successfully treated with tacrolimus and prednisolone combination therapy. The mechanism of IC, including the involved autoimmunity, has not been elucidated. Clinical observation studies suggest a potential association between SS and IC. However, IC is currently thought to be underdiagnosed in patients with SS as well as in the general population. Based on our case and others reported previously, IC associated with SS responds well to immunosuppressive therapy. In particular, a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) with a corticosteroid seems to be highly effective. The possibility of IC in patients with SS complaining of lower urinary tract symptoms without features of infection or other identifiable causes should be given attention. [ABSTRACT FROM AUTHOR]

To evaluate the eff ects of tocilizumab (TCZ) on adult-onset Still's disease (AOSD), we reviewed medical records of seven patients with refractory AOSD treated with TCZ at our institution. TCZ therapy might allow rapid corticosteroid tapering and help maintain remission status, that is, resolution of clinical symptoms and normalization of biomarkers such as CRP and ferritin. Patients, however, should be monitored for the development of macrophage activation syndrome when TCZ is administered for active AOSD. [ABSTRACT FROM AUTHOR]

A highly soluble cocrystal of a poorly soluble drug has the potential to improve the dissolution rate and bioavailability. Reaping the potential dissolution advantage of soluble cocrystals is challenged by the precipitation of the parent drug during dissolution. Using the carbamazepine-nicotinamide cocrystal, we show that the use of excess coformer can be an effective strategy for eliminating precipitation during dissolution by taking advantage of the "common coformer effect". When excess coformer is present, the solubility of the cocrystal is depressed, which leads to a lower degree of supersaturation. At an appropriate level, precipitation can be prevented and improved dissolution is realized. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the utility of imaging techniques, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), in immunoglobulin (IgG)4-related disease (IgG4-RD). Methods: We reviewed eight IgG4-RD patients who were referred to our hospital between August 2006 and April 2012. All cases underwent FDG-PET/CT and brain magnetic resonance imaging (MRI) and endobronchial ultrasonography (EBUS) were also performed in five cases and one case, respectively. Results: Although nearly all patients with IgG4-RD in this study were negative for CRP (mean 0.22mg/dL), various organ involvement sites were detected by FDG-PET/CT. In the active phase in two autoimmune pancreatitis (AIP) cases, FDG-PET/CT showed longitudinal and heterogeneous FDG accumulation in the pancreas with FDG uptake in the hilar or mediastinal lymph nodes. Follow-up FDG-PET/CT after therapy in one case revealed that the abnormal FDG uptake in all affected lesions had completely disappeared. In two cases, brain MRI revealed asymptomatic hypertrophic pachymeningitis. In one case, EBUS imaging of mediastinal lymph node swelling was consistent with tortuous vessels with high Doppler signals and hyperechoic strands between lymph nodes. Conclusions: When FDG-PET/CT shows FDG accumulation, characteristic of IgG4-RD in organs, without evidence of an associated inflammatory reaction, a diagnosis of IgG4-RD can be made. Treatment effects can be assessed by the disappearance of FDG uptake. A routine brain MRI is useful for detecting asymptomatic hypertrophic pachymeningitis. EBUS may also be useful for differentiating among the etiologies of lymphadenopathy with characteristic sonographic imaging findings. [ABSTRACT FROM AUTHOR]

Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves' disease. She was diagnosed with Graves' disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves' disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves' disease, few reports about thyroid cancer accompanied by Graves' disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves' disease. [ABSTRACT FROM AUTHOR]

Abstract  Among the isotypes of serum tartrate-resistant acid phosphatase (TRACP), only type 5b (TRACP-5b) is derived from osteoclasts, and it is necessary to develop an assay specific for this TRACP-5b for evaluation of osteoclastic activity. Recently, a novel assay system for TRACP-5b called the fragments absorbed immunocapture enzymatic assay (FAICEA) has been developed. With two unique monoclonal antibodies, one that is highly specific for TRACP-5b and another which absorbs inactive TRACP-5b fragments that interfere with measuring active TRACP-5b, this assay provides correct measurement of TRACP-5b activity in the serum without interference by the inactive fragments of TRACP-5b and other isotypes of TRACP, especially TRACP-5a. To study the reference data of Japanese subjects, we measured TRACP-5b activity in the serum of 320 men (age, 20–82 years) and 466 women [315 premenopausal (age, 18–55 years) and 151 postmenopausal (age, 45–77 years)] with this novel assay. In men, serum TRACP-5b activity did not vary significantly with age. The postmenopausal women had significantly higher serum TRACP-5b activity than the premenopausal women. The reference intervals (logarithmic mean ±1.96 SD) for men, premenopausal women, and postmenopausal women were 1.7–5.9 U/l, 1.2–4.4 U/l, and 2.5–7.6 U/l, respectively. [ABSTRACT FROM AUTHOR]

Abstract Purpose  To find out if the whole parathyroid hormone (wPTH) assay has practical advantages over the intact (iPTH) assay in patients with Graves’ disease. Methods  We measured iPTH and wPTH levels before and after subtotal thyroidectomy in 111 consecutive patients (94 women and 17 men) with Graves’ disease. Blood samples for assays were obtained after the induction of anesthesia (basal) and following skin closure (postoperative). Results  There was a significant correlation between wPTH and iPTH in both the basal and postoperative levels. Logistic regression analyses examining the relationship between the reduction in parathyroid hormone (PTH) levels and the incidence of tetany revealed that both the wPTH and iPTH assays were significantly equally predictive of postoperative tetany. Conclusion  We found that both the wPTH and iPTH assays were useful for predicting postoperative tetany in patients with Graves’ disease, yielding similar results. [ABSTRACT FROM AUTHOR]

To investigate the interrelationship between polyamine and ethylene, apple fruits (Malus domestica Borkh.) were treated with 1-methylcyclopropene (1-MCP). Without 1-MCP treatment, ethylene production of apple fruits rapidly increased to maximum level at 4 days after treatment (DAT) and kept its level until 21 DAT, then gradually decreased. Accordingly, fruit firmness was progressively reduced until 26 DAT. On the other hand, ethylene production in 1-MCP-treated fruits was almost completely repressed until 21 DAT, retaining fruit firmness. This ethylene inhibition by 1-MCP was accompanied by the reduction of transcript accumulations for 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) and ACC oxidase (ACO). The expression of MdSAMDC1 showed no differences between 1-MCP-treated and control fruits, whereas that of MdSAMDC2 was rather repressed in 1-MCP-treated fruits compared with the control. There were no statistically significant differences of free spermidine (Spd) and spermine (Spm) titers between fruits with and without 1-MCP treatment; however, Spd titer in 1-MCP-treated fruits temporally increased in the early DAT, then was adjusted to similar level as that in control, whereas Spm level was always higher in 1-MCP-treated fruits than in the control, indicating that Spd may be under a tight homeostatic regulation, whereas Spm may not. Therefore, the results demonstrated that the antagonistic relationships between polyamine and ethylene might exist transiently in the early days after 1-MCP treatment, but disappear later possibly because of the polyamine homeostasis mechanism and the extension of apple shelf life by 1-MCP might be owed little to the role of polyamines and be mainly ascribed to the inhibitory effects of ethylene on modulation of all wall. [ABSTRACT FROM AUTHOR]

We describe our modification of the reversed T-shaped sternotomy. The conventional technique consists of a limited upper sternotomy with transverse division of the sternum. Our modification involves shifting the transverse division lines one costal space between the right and left sides for perfect apposition of the divided upper and lower sternum. This technique can be used for patients with thyroid cancer and mediastinal lymph node metastasis and for those with a mediastinal tumor or certain cardiac disorders. [ABSTRACT FROM AUTHOR]

Low-density InAs quantum dots (QDs) were grown by intermittent supply method in molecular beam epitaxy. QD density was controlled in a wide range of 106 to 109 cm−2 by in-situ monitoring of RHEED specular-beam intensity. Low-density InAs QDs were embedded into GaAs/AlAs micro-pillar cavity structure, which was fabricated by anisotropic wet-etching through a conventional photoresist mask. Photoluminescence (PL) spectra of single InAs QD in the micro-cavity were analyzed, and its PL intensity was three times higher than that without the cavity. [ABSTRACT FROM AUTHOR]