Ultrasound-guided fine-needle aspiration of thyroid nodules: assessment of the ideal number of punctures

OBJECTIVE: To determine the number of punctures in fine-needle aspiration biopsies required for a safe cytological analysis of thyroid nodules. MATERIALS AND METHODS: Cross-sectional study with focus on diagnosis. The study population included 94 patients. RESULTS: The mean age of the patients participating in the study was 52 years (standard-deviation = 13.7) and 90.4% of them were women. Considering each puncture as an independent event, the first puncture has showed conclusive results in 78.7% of cases, the second, in 81.6%, and the third, in 71.8% of cases. With a view to the increasing chance of a conclusive diagnosis at each new puncture, two punctures have showed conclusive results in 89.5% of cases, and three punctures, in 90.6% of cases with at least one conclusive result. CONCLUSION: Two punctures in fine-needle aspiration biopsies of thyroid nodules have lead to diagnosis in 89.5% of cases in the study sample, suggesting that there is no need for multiple punctures to safely obtain the diagnosis of thyroid nodules.

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND: Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS: The study consisted of consecutive fine-needle aspiration biopsy (FNAB) cases collected between January 1, 2013 and June 30, 2014 from 5 academic institutions. Demographic information, cytology diagnoses, and surgical pathology follow-up were recorded. The ROM was calculated with and without NI-FVPTC and was presented as a range: all cases (ie, overall risk of malignancy [OROM]) versus those with surgical follow-up only. RESULTS: The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. CONCLUSIONS: The results from this multi-institutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC. Cancer Cytopathol 2016;124:181-187. © 2015 American Cancer Society.

Is there any association between Hashimoto’s thyroiditis and thyroid cancer? A retrospective data analysis

AbstractObjective:To evaluate the association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC).Materials and Methods:The patients were evaluated by ultrasonography-guided fine needle aspiration cytology. Typical cytopathological aspects and/or classical histopathological findings were taken into consideration in the diagnosis of HT, and only histopathological results were considered in the diagnosis of PTC.Results:Among 1,049 patients with multi- or uninodular goiter (903 women and 146 men), 173 (16.5%) had cytopathological features of thyroiditis. Thirty-three (67.4%) out of the 49 operated patients had PTC, 9 (27.3%) of them with histopathological features of HT. Five (31.3%) out of the 16 patients with non-malignant disease also had HT. In the groups with HT, PTC, and PCT+HT, the female prevalence rate was 100%, 91.6%, and 77.8%, respectively. Mean age was 41.5, 43.3, and 48.5 years, respectively. No association was observed between the two diseases in the present study where HT occurred in 31.1% of the benign cases and in 27.3% of malignant cases (p = 0.8).Conclusion:In spite of the absence of association between HT and PCT, the possibility of malignancy in HT should always be considered because of the coexistence of the two diseases already reported in the literature.

Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast

Calcium signals trigger the translocation of the Prz1 transcription factor from the cytoplasm to the nucleus. The process is regulated by the calciumactivated phosphatase calcineurin, which activates Prz1 thereby maintaining active transcription during calcium signalling. When calcium signalling ceases, Prz1 is inactivated by phosphorylation and exported to the cytoplasm. In budding yeast and mammalian cells, different kinases have been reported to counter calcineurin activity and regulate nuclear export. Here, we show that the Ca2+/calmodulin-dependent kinase Cmk1 is first phosphorylated and activated by the newly identified kinase CaMKK2 homologue, Ckk2, in response to Ca2+. Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca2+. Furthermore, Cdc25 phosphatase is also phosphorylated by Cmk1, inducing cell cycle arrest in response to an increase in Ca2+. Moreover, cmk1 deletion shows a high tolerance to chronic exposure to Ca2+, due to the lack of cell cycle inhibition and elevated Prz1 activity. This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription. These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.

Design of highly focused fields that remain unpolarized on axis

Research on the properties of highly focused fields mainly involved fully polarized light, whereas partially polarized waves received less attention. The aim of this Letter is to provide an appropriate framework, for designing some features of the focused field, when dealing with incoming partially polarized beams. In particular, in this Letter, we describe how to get an unpolarized field on the axis of a high numerical aperture objective lens. Some numerical results that corroborate theoretical predictions are provided.

Added value of SPECT/CT in addition to whole-body scintigraphy augmented with prone lateral views in patients with well-differentiated thyroid carcinoma

Purpose: We aimed to determine the impact of SPECT/CT performed in addition to whole-­‐body scintigraphy augmented with prone lateral views in patients with well-­‐differentiated thyroid carcinoma. Methods and Materials: This retrospective study included 141 patients (87 female, 54 male, mean age 47 years) with well-­‐differentiated thyroid carcinoma (105 papillary, 31 follicular, 1 Hürthle cell and 4 poorly differentiated) treated with radioiodine therapy (1000-7400 MBq). Patients were referred for either first postsurgical therapy (n=76) or further treatment (n=65). Two nuclear medicine physicians interpreted the scans in consensus (first whole-­‐body scintigraphy with prone lateral view, then SPECT/CT) reporting abnormal iodine uptake in the thyroid bed, lymph nodes and distant metastasis. The corresponding ATA risk score was calculated for each patient before and after SPECT/CT, as well as change in disease extension Results: The analysis showed a difference between scintigraphy and SPECT/CT in n=17 lesions in 14 patients (9.9%): 12 were described as suspicious on scintigraphy and could be considered as benign on SPECT/CT (3 corresponded to local iodine uptake, 6 to lymph nodes metastases and 3 to distant metastases). The others 5 corresponded to metastases (4 lymph nodes and 1 distant) that were not seen on whole-­‐body scintigraphy augmented with prone lateral views. In 10 of 141 (7.1%) patients, we observed a change in ATA risk stratification, with a risk increase in 4 of them (2.8%). Conclusion: SPECT/CT allowed detecting 5 focal lesions missed on planar scintigraphy, and to precise benignity of 12 suspicious lesions on planar scintigraphy. Moreover, SPECT/CT improved the risk stratification in 10 patients with a significant change in the patient management

Regulating Mechanisms of Gonadal and Pituitary Tumorigenesis in Mice Producing Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are structurally and functionally similar glycoprotein hormones acting through the same luteinizing hormone chorionic gonadotropin receptor (LHCGR). The functions of LH in reproduction and hCG in pregnancy are well known. Recently, the expression of LHCGR has been found in many nongonadal tissues and cancers, and this has raised the question of whether LH/hCG could affect the function or tumorigenesis of these nongonadal tissues. We have also previously generated an hCG expressing mouse model presenting nongonadal phenotypes. Using this model it is possible to improve our understanding of nongonadal action of highly elevated LH/hCG. In the current study, we analyzed the effect of moderately and highly elevated hCG levels on male reproductive development and function. The main finding was the appearance of fetal Leydig cell (FLC) adenomas in prepubertal males. However, the development and differentiation of FLCs were not significantly affected. We also show that the function of hCG is different in FLCs and in adult Leydig cells (ALC), because in the latter cells hCG was not able to induce tumorigenesis. In FLCs, LHCGR is not desensitized or downregulated upon ligand binding. In this study, we found that the testicular expression of two G protein-coupled receptor kinases responsible for receptor desensitization or downregulation is increased in adult testis. Results suggest that the lack of LHCGR desensitization or downregulation in FLCs protect testosterone (Te) synthesis, but also predispose FLCs for LH/hCG induced adenomas. However, all the hCG induced nongonadal changes observed in male mice were possible to explain by the elevated Te level found in these males. Our findings indicate that the direct nongonadal effects of elevated LH/hCG in males are not pathophysiologically significant. In female mice, we showed that an elevated hCG level was able to induce gonadal tumorigenesis. hCG also induced the formation of pituitary adenomas (PA), but the mechanism was indirect. Furthermore, we found two new potential risk factors and a novel hormonally induced mechanism for PAs. Increased progesterone (P) levels in the presence of physiological estradiol (E2) levels induced the formation of PAs in female mice. E2 and P induced the expression and nuclear localization of a known cell-cycle regulator, cyclin D1. A calorie restricted diet was also able to prevent the formation of PAs, suggesting that obesity is able to promote the formation of PAs. Hormone replacement therapy after gonadectomy and hormone antagonist therapy showed that the nongonadal phenotypes observed in hCG expressing female mice were due to ovarian hyperstimulation. A slight adrenal phenotype was evident even after gonadectomy in hCG expressing females, but E2 and P replacement was able to induce a similar phenotype in WT females without elevated LH/hCG action. In conclusion, we showed that the direct effects of elevated hCG/LH action are limited only to the gonads of both sexes. The nongonadal phenotypes observed in hCG expressing mice were due to the indirect, gonadal hormone mediated effects of elevated hCG. Therefore, the gonads are the only physiologically significant direct targets of LHCGR signalling.

Evolution in the profile of thyroid cancer cases treated in an oncology reference service: what changed in the last 20 years

Objective: To evaluate the characteristics of thyroid carcinoma cases treated at a reference hospital for cancer between 2008 and 2010.Methods: we studied 807 cases and analyzed the following clinicopathologic variables: symptoms, risk factors, diagnostic tests, staging, histological type, treatment performed and complications.Results: Females were more affected, with 660 cases (82%). The average age at diagnosis was 44.5 years. Prior exposure to ionizing radiation was reported by 22 (3%) patients, a family history of thyroid cancer by 89 (11%), and 289 (36%) individuals reported other types of cancer in the family. The fine needle aspiration biopsy was the main parameter for surgical indication and was suggestive of carcinoma in 463 patients (57%). Papillary carcinoma was the most common histological type, with 780 cases (96.6%). There were 728 (90%) total thyroidectomies, 43 (5.3%) reoperations or partial thyroidectomies followed by totalization, 23 (2.8%) extended thyroidectomies and only 13 (1.6%) partial thyroidectomies (lobectomy with isthmectomy). Neck dissection associated with thyroidectomy was done in 158 patients (19.5%). We observed a predominance of tumors classified as T1 in 602 (74.6%) patients. Transient hypocalcemia was the most frequent complication.Conclusion: The results show that the worldwide increase in the incidence of thyroid cancer has changed the profile of patients seen at a referral service. In addition, there were changes in the type of surgical treatment used, with increased use of total thyroidectomy in relation to partial and subtotal ones, and decreased use of elective neck dissections.

Role of the canonical transient receptor potential channel 2 (TRPC2) in thyroid cell function

Kalciumjonen reglerar flera processer i celler såsom transkribering av gener, celldelning, cellernas rörlighet och celldöd. Därför har cellerna utvecklat många mekanismer för att reglera den intracellulära kalciumkoncentrationen. Kalciumkanaler spelar en viktig roll i denna regleringsprocess. TRPC-kanalerna (eng. canonical transient receptor potential) är en familj av jonkanaler med sju medlemmar (TRPC1-7) vars regleringsmekanismer och fysiologiska roller är varierande. TRPC2-kanalens fysiologiska signifikans, samt hur kanalen regleras, är dåligt karakteriserad. För första gången, rapporterar vi närvaron av TRPC2 kanalen i råttans sköldkörtelceller samt primära sköldkörtelceller från råtta. Hos gnagare har TRPC2 antagits vara exklusivt uttryckt i det vomeronasala organet. För att undersöka den fysiologiska betydelsen av kanalen, har vi utvecklat stabila celler med nedreglerat TRPC2 (shTRPC2) m.h.a. shRNA-teknik. Nedreglering av TRPC2 resulterade i stora skillnader i flera viktiga cellulära funktioner och i regleringen av sköldkörtelcellernas cellsignalering. Nedreglering av TRPC2 orsakade minskad agonist-beroende frigivning av kalcium från det endoplasmatiska nätverket, samt minskat agonist-beroende inflöde av extracellulärt kalcium, men ökade det basala kalciuminflödet. Uttrycket av PKCβ1 och PKCδ, SERCA-aktiviteten och kalciumhalten i det endoplasmatiska nätverket minskade i shTRPC2 celler. Kommunikation mellan kalcium- och cAMP-signalering påvisades vara TRPC2-beroende, vilket visades reglera uttrycket av TSH-receptorn. Vi undersökte också betydelsen av TRPC2 kanalen i reglering av sköldkörtelcellers proliferation, migration, vidhäftning och invasion; processer som alla var dämpade i shTRPC2 celler. Samamnfattningsvis påvisade dessa resultat en ny och viktig fysiologisk betydelse för TRPC2 kanalerna.

Multi-axis solutions in packaging machines in Europe

The objective of this thesis was to examine the potential of multi-axis solutions in packaging machines produced in Europe. The definition of a multi-axis solution in this study is a construction that uses a common DC bus power supply for different amplifiers running the axes and the intelligence is centralized into one unit. The cost structure of a packaging machine was gained from an automation research, which divided the machines according to automation categories. The automation categories were then further divided into different sub-components by evaluating the ratio of multi-axis solutions compared to other automation components in packaging machines. A global motion control study was used for further information. With the help of the ratio, an estimation of the potential of multi-axis solutions in each country and packaging machine sector was completed. In addition to the research, a specific questionnaire was sent to five companies to gain information about the present situation and possible trends in packaging machinery. The greatest potential markets are in Germany and Italy, which are also the largest producers of packaging machinery in Europe. The greatest growth in the next few years will be seen in Turkey where the annual growth rate equals the general machinery production rate in Asia. The greatest market potential of the Nordic countries is found in Sweden in 35th position on the list. According to the interviews, motion control products in packaging machines will retain their current power levels, as well as the number of axes in the future. Integrated machine safety features together with a universal programming language are the desired attributes of the future. Unlike generally in industry, the energy saving objectives are and will remain insignificant in the packaging industry.

Morphological and immunohistochemical characterization of angiogenic and apoptotic factors and the expression of thyroid receptors in the ovary of tilapia Oreochromis niloticus in captivity

Morphological and immunohistochemical characterization of angiogenic and apoptotic factors and the expression of thyroid receptors in the ovary of tilapia Oreochromis niloticus in captivity were studied. The morphological evaluation of the ovaries was performed by histological paraffin embedded and stained with HE. The immunohistochemical expressions of CDC47, VEGF, Flk-1, angiopoietin, Tie-2 and thyroid receptor (TRα) were performed by the technique of streptavidein-biotin-peroxidase. Apoptosis was assessed using the TUNEL kit. The relative expression of thyroid hormone receptors (TRα and TRβ) was assessed by RT-PCR real time. The nuclear expression of CDC47 increased with the stage of maturation of the oocyte and was observed in the follicle cells. Apoptotic bodies were observed in the follicular cells of atretic follicles and postovulatory follicles from the ovaries of 150g and 350g fish. Expression of VEGF and its receptor Flk-1 was also observed in the follicular cells, and the expression of both increased with the maturity of the oocyte, with a higher intensity observed in the full-grown follicle. The expression of angiopoietin and of its receptor (Tie 2) was discrete and moderate respectively. TRα expression was independent of follicular development. However, the 350 g tilapia exhibited higher expression of TRβ compared with the 50 g tilapia. We conclude that the proliferative activity and the expression of VEGF and its receptor increase with follicular maturation and that the TRs expression increases with ovarian maturity in tilapia (Oreochromis niloticus).

Single axis controlled attraction type magnetic bearing

This paper presents a new type of magnetic bearing with active control only in axial direction. The bearing uses two pairs of permanent magnets working in attraction mode to restrict the radial motion and a control system composed of two electromagnets, a gap sensor and a controller to keep the axis in a fixed axial position. The principle, the dynamic model for axial motion and the control system for this bearing are presented. Finally, by experiments conducted in a prototype, the effectiveness of the presented concept is shown.