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Introduction Hurthle cells are modified follicular thyroid cells, whose development and proliferation have been related to different stimuli inducing cellular stress. Most thyroid aspirates containing Hurthle cells are classified as indeterminate, although the specific risk of malignancy for this subtype of atypia remains unclear. The aim of our study was to assess if the presence of Hurthle cells in indeterminate thyroid nodules correlates with the risk of malignancy. We further evaluated if this risk can be modified by the presence of an underlying Hashimoto's thyroiditis. Materials and methods We retrospectively analyzed all indeterminate thyroid nodules that were surgically treated at our institution between January 2010 and March 2019. For each nodule, we inferred the presence of Hurthle cells in the cytological report. Cytological findings were then correlated with histological reports. Results 354 indeterminate thyroid nodules were included in the study. The rate of malignancy resulted significantly lower in nodules exhibiting Hurthle cells compared to those negative for this cellular pattern (11.4% vs 22.5%, p = 0.01). Although there was no difference in the rate of malignancy in the whole population according to the presence or absence of Hashimoto's thyroiditis (21.5 vs 18.5%, p = 0.63), the significantly lower prevalence of malignant lesions in nodules with Hurthle cells was confirmed only in the presence of a histologically documented Hashimoto's thyroiditis (6.2% vs 32%, p = 0.005). Conclusions The finding of Hurthle cells in indeterminate thyroid nodules is associated with a low risk of malignancy in patients with an underlying Hashimoto's thyroiditis. The clinical management of these lesions may therefore be more conservative.

The Pound–Drever–Hall technique is widely used for laser frequency or optical cavity length stabilization. We propose a method to broaden its dynamic range. The conventional error signal divided by the transmission power serves as the new error signal, which increases the dynamic range in the linear regime. The use of an extended Kalman filter improves the resilience to noise when the transmitted power is low. This expands the dynamic range into the nonlinear regime and achieves a deterministic auto-lock even in the presence of a large disturbance. Such a nonlinear extension is, however, limited to an auto-lock for a previously locked state because the extended Kalman filter requires accurate prior knowledge of the initial state. For demonstration purposes, we simulate the implementation of this method for locking a ten-meter scale cavity with a single-stage suspension.

Background. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system changed the age cutoff for risk stratification of differentiated thyroid carcinoma (DTC), downgrading patients between 45 and 54 years to stage I or II. The aim of our study was to assess cancer-specific survival (CSS) in patients aged 45–54 years, in order to document the prognostic capability of the last edition of the staging system. Methods. We retrospectively reviewed the medical records of 172 patients that from January 1st, 2005, to May 31st, 2017, were diagnosed at our institution with DTC when aged 45–54 years. We restaged patients according to the 8th edition of the staging system and estimated CSS. Results. 101 out of 172 patients (58.7%) were reallocated to a lower stage. Of the 101 downstaged patients, 88 (88.9%) showed a high or intermediate American Thyroid Association (ATA) risk of recurrence. We recorded no cancer-specific deaths. Conclusions. Risk of cancer-specific mortality in patients aged 45–54 years with DTC is low, supporting the prognostic capability of the 8th edition of the staging system. However, we recommend to consider carefully the significant proportion of patients at intermediate or high risk of recurrence in this group of patients.

Tumors of the parathyroid glands are highly vascularized and display a microRNA (miRNA) profile divergent from normal parathyroid glands (PaNs). Angiogenic miRNAs, namely miR-126-3p, miR-126-5p, and miR-296-5p, have been found downregulated in parathyroid tumors. Here, we show that miR-126-3p expression levels are reduced in parathyroid adenomas (PAds; n = 12) compared with PaNs (n = 4). In situ hybridization (ISH) of miR-126-3p and miR-296-5p in 10 PAds show that miR-126-3p is expressed by endothelial cells lining the walls of great vessels and by cells within the thin stroma surrounding acinar structures. At variance, miR-296-5p was detectable in most PAd epithelial cells. Combining ISH for miR-126-3p with immunohistochemistry for the endothelial and mesenchymal markers CD34, CD31 and α-smooth muscle actin (αSMA), we could identify that miR-126-3p is localized in the αSMA-positive thin stroma. Further, miR-126-3p-expressing cells are enriched in the CD34-positive stromal cells surrounding epithelial cell acinar structures, a cellular pattern consistent with tumor-associated myofibroblasts (TAMs). In line with this, CD34-positive cells, sorted by FACS from PAds tissues, express miR-126-3p at higher levels than CD34-negative cells, suggesting that miR-126-3p downregulation promotes the endothelial-to-αSMA+ mesenchymal transition. In human mesenchymal stem cells derived from bone marrow (hBM-MSCs), a model of TAMs, the co-culture with PAds-derived cells for 5 days decreases miR-126-3p, while it increases VEGFA expression. At variance, adrenomedullin (ADM) expression is unaffected. Finally, overexpression of the miR-126-3p mimic in both hBM-MSCs and PAds-derived explants downregulates VEGFA expression levels. In conclusion, miR-126-3p is expressed by both endothelial cells and TAMs in PAds, and its downregulation promotes neoangiogenesis, possibly through VEGFA overexpression.

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging system changed the age cutoff for risk stratification of differentiated thyroid carcinoma (DTC), downgrading patients between 45 and 54 years to stage I or II. The aim of our study was to assess cancer-specific survival (CSS) in patients aged 45–54 years, in order to document the prognostic capability of the last edition of the staging system. Methods We retrospectively reviewed the medical records of 172 patients that from January 1st, 2005, to May 31st, 2017, were diagnosed at our institution with DTC when aged 45–54 years. We restaged patients according to the 8th edition of the staging system and estimated CSS. Results 101 out of 172 patients (58.7%) were reallocated to a lower stage. Of the 101 downstaged patients, 88 (88.9%) showed a high or intermediate American Thyroid Association (ATA) risk of recurrence. We recorded no cancer-specific deaths. Conclusions Risk of cancer-specific mortality in patients aged 45–54 years with DTC is low, supporting the prognostic capability of the 8th edition of the staging system. However, we recommend to consider carefully the significant proportion of patients at intermediate or high risk of recurrence in this group of patients.

The valorization of food wastes is a challenging opportunity for a green, sustainable, and competitive development of industry. Approximately 30 million m3 of olive mill wastewater (OMWW) are produced annually in the world as a by-product of the olive oil extraction process. In addition to being a serious environmental and economic issue because of their polluting load, OMWW can also represent a precious resource of high-added-value molecules such as polyphenols that show acclaimed antioxidant and anti-inflammatory activities and can find useful applications in the pharmaceutical industry. In particular, the possibility to develop novel nutraceutical ophthalmic formulations containing free radical scavengers would represent an important therapeutic opportunity for all inflammatory diseases of the ocular surface. In this work, different adsorbents were tested to selectively recover a fraction that is rich in polyphenols from OMWW. Afterward, cytotoxicity and antioxidant/anti-inflammatory activities of polyphenolic fraction were evaluated through in vitro tests. Our results showed that the fraction (0.01%) had no toxic effects and was able to protect cells against oxidant and inflammatory stimulus, reducing reactive oxygen species and TNF-&alpha, levels. Finally, a novel stable ophthalmic hydrogel containing a polyphenolic fraction (0.01%) was formulated and the technical and economic feasibility of the process at a pre-industrial level was investigated.

Insufficient vascular supply is one of the main causes of anastomotic leak in colorectal surgery. Intraoperative indocyanine-green (ICG) angiography has been shown to provide information on tissue perfusion, identifying a well-perfused location for colonic and rectal transections, and thus possibly reducing the leak rate. Aim of this study was to evaluate the usefulness of intraoperative assessment of anastomotic perfusion using ICG angiography in patients undergoing left-sided colon or rectal resection with colorectal anastomosis. This randomized trial involved 252 patients undergoing laparoscopic left-sided colon and rectal resection randomized 1:1 to intraoperative ICG or to subjective visual evaluation of the bowel perfusion without ICG. The primary aim was to assess whether ICG angiography could lead to a reduction in anastomotic leak rate. Secondary outcomes were possible changes in the surgical strategy and postoperative morbidity. After randomization, 12 patients were excluded. Accordingly, 240 patients were included in the analysis; 118 were in the study group, and 122 in the control group. ICG angiography showed insufficient perfusion of the colic stump, which led to extended bowel resection in 13 cases (11%). An anastomotic leak developed in 11 patients (9%) in the control group and in 6 patients (5%) in the study group (p = n.s.). Intraoperative ICG fluorescent angiography can effectively assess vascularization of the colic stump and anastomosis in patients undergoing colorectal resection. This method led to further proximal bowel resection in 13 cases, however, there was no statistically significant reduction of anastomotic leak rate in the ICG arm. ClinicalTrials.gov NCT02662946.

The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1(MEN1), while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61, CTGF, and WNT5A, and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.

The olive oil industry is a sector of high relevance in the economy of the European Union; indeed, three quarters of the world production is concentrated in the South Europe. Unfortunately, the commonly used milling techniques generate huge amounts of highly polluting olive mill wastewater (OMWW) as a side-product. If released in the environment, not treated OMWW have a detrimental impact on land and water because of the large amount of phytotoxic phenolic compounds contained. At the same time, due to their powerful antiradical properties, polyphenols represent the center of a very valuable market niche, where they find application in cosmetic and nutraceutic fields. Consequently, the mandatory (for evident environmental reasons) depollution of OMWW associated with an efficient and selective recovery of the phenolic fraction could be economically very advantageous. In the present study, a new methodology employing activated charcoal as the adsorbent phase was developed in order to depollute OMWW and simultaneously recover a fraction enriched in hydroxytyrosol, the most abundant and valuable phenolic compound present in this matrix. Moreover, to evaluate the technical and economic feasibility of the process at a pre-industrial level, this strategy was submitted to a scale-up process and a pilot plant prototype was developed.

The use of biological species in the monitoring of marine environmental quality allows the evaluation of biologically available levels of contaminants in the ecosystem and the effects of contaminants on living organisms. The seagrass Posidonia oceanica is a useful bioindicator because through the lepidochronology technique it is possible to obtain a historical contamination trend of a given area. This study aims to assess the temporal trend contamination by heavy metal investigations on dead sheaths of 100 samples of P. oceanica collected in the Protected Marine Area of "Plemmirio" (Sicily) and in the Siracusa bay. Important results were obtained because data show a significant negative temporal trend for the metals analysed especially for As, Co, Cr, Hg, Pb, Se, U and V that in the past had higher concentrations, with a stronger contamination in the Plemmirio area, the site much more exposed to the pollution of the nearby petrochemical complex. This study confirms the relevance of the use of P. oceanica as a biological indicator of metal contamination in coastal ecosystems. Thus the usefulness of P. oceanica as a tracer of spatial metal contamination and as a good tool for water quality evaluation is reinforced.

The olive oil industry is a sector of high relevance in the economy of the European Union; indeed, three quarters of the world production is concentrated in Europe. The extraction of olive oil generates huge quantities of wastes that may have a great impact on land and water environments because of their high phytotoxicity. Olive mill wastewater (OMW) represents the main by-product. Approximately 30 million m3of OMW are produced annually just in the Mediterranean area, and a direct reuse of this wastewater in agriculture is strongly limited by the phytotoxicity and antimicrobial effects due in particular to its contents in phenolic compounds, and low pH (4 - 5). However polyphenols are characterized by an important antioxidant activity; therefore, once extracted from OMW, they might find valorization in the cosmetic and pharmaceutical industries, in food technologies, and conversely the physico-chemical parameters of the resulting clarified waters could be much more compatible for a reuse in agriculture. One of the most abundant and important polyphenols contained in OMW is hydroxytyrosol (3,4-dihydroxyphenylethanol) characterized by a very interesting and documented antioxidant activity. In the present study, activated charcoal was applied as adsorbent to clarificate OMW and simultaneously to recover an hydroxytyrosol enriched fraction; optimization and recycle of the adsorbent material was studied too. Moreover to evaluate the feasibility and the economic value at industrial level, the procedure was submitted to a scale-up process and an automatized pilot prototype was developed.

The protonation of 3-amino-1,2,4-triazole was studied potentiometrically (glass electrode) in sodium chloride and calcium chloride solutions, 0.13 I 0.92M, at 10, 25, 37 and 45 degrees . The effect of the background electrolyte on the protonation constants is explained by a complex formation model. The species CaL(+), CaHL(2+) and H(2)LCl (HL = 3-amino-1,2,4-triazole) are proposed. Stability constants, together with their dependence on temperature (DeltaH degrees ) and on ionic strength, are reported for the protonated and complex species.

The formation constants of copper(II) complexes of phenoxyacetate, 2-phenoxypropionate and 2-phenoxybutyrate were determined potentiometrically, using an (H + )-glass electrode at 10, 25, 37 and 45 °C, at different ionic strengths in the range 0.05 ⩽ I ⩽ 0.3 mol l −1 . Values for Δ H XXX and Δ S XXX were estimated from the temperature coefficients. Using the formation constants obtained, together with literature results for low molecular weight monocarboxylate ligands, a simple linear relationship between formation and protonation constants was obtained.

Formation and stability of the mixed complexes of Cu 2+ -2, 2′-dipyridyl with cyclohexane-1, 1-dicarboxylic acid have been investigated by means of potentiometric measurements of hydrogen ion concentration, at 25° C and in a medium 0.1M (Na,H)ClO 4 . Complexes as CuDipL and CuDipL 2 have been considered. Hamilton test applied to this system cannot confirm or exclude the hypothesis of formation of the complex CuDipL 2 , whose real existence is considered unlikely on the ground of enthalpic and entropic considerations. Relating the stability of CuDipL to that of other mixed complexes of CuDip L with some 1, 1-dicarboxylic acids previously studied one can point out the influence of the alicyclic ring rigidity on the stability of the mixed complexes.

The thermal behaviour of mixed complexes containing transition metals, α-nitroketones and pyridine or ethanol was investigated by thermogravimetric analysis (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC). The values of the activation energies and the enthalpies for the dissociation processes have been calculated in high vacuum and isothermal conditions. Comments are made on the obtained heats and correlations with structural characteristics are looked for.

A new digital timer for electrocapillary studies, which allows to time a predeterminate number of consecutive drops up to 99.999s, is described. The instrument was checked against 1MKCl and 0.1 M NaF solutions and the experimental results obtained this way are discussed.

The polarographic behaviour of isothionicotinamide in aqueous-organic system and at various values of pH has been studied. The reaction pattern has been explained on the basis of the protolytic equilibria and surface activity of the depolarizer.

A simple computer program (DISDI) has been developed for obtaining the distribution diagrams of the species in solutions containing up to one metal and two ligands. It has been compared with the programs COMICS and EQUIL.