Influence of different palatal morphologies on the accuracy of intraoral scanning of the edentulous maxilla: A three-dimensional analysis.

PURPOSE: This study investigated the influence of different palatal morphologies on the accuracy of intraoral scanning (TRIOS 4) of edentulous maxillae. METHODS: Six typodonts were fabricated for different palatal morphologies with flat (F), medium (M), and deep (D) palates, with palatal wrinkles (W), or smooth palates (S), resulting in six groups: WF, WM, WD and SF, SM, SD. Ten scans were performed for each group; standard tessellation language files obtained were imported into a software to measure trueness and precision in micrometer. Trueness was calculated as the mean of the standard deviation values obtained by superimposing each scan onto the reference scan. Precision was achieved by overlapping each scan with that with the best trueness in the group. Descriptive and post-hoc analyses were conducted. RESULTS: The mean values for trueness were as follows: WM=48.7±4.7, WD=161.7±18.4, WF=85.9±16, SM=48.1±2.4, SD=349.9±8.8, and SF=349.1±25.5. The precision values were as follows: WM=46.7±7.3, WD=46.9±9, WF=48.9±6.7, SM=46±2.7, SD=105.9±17.4, SF=72.6±10.8. Significant differences were observed for trueness between SM and SD (P < 0.001), SM and SF (P < 0.001), and WF and SF (P = 0.003); whereas for precision, significant differences were reported between WD and SD (P = 0.015). Regarding trueness and precision, no difference was found between WM and SM (P = 1.0). CONCLUSIONS: Medium palatal depth showed the best accuracy. The mean accuracy values were within the clinical acceptability thresholds for all palatal morphologies. The presence of rugae improved the precision of deeper palates and the trueness of flat palates. No differences were observed in the medium palates with or without rugae.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

Preconception Thyrotropin Levels and Thyroid Function at Early Gestation in Women With Hashimoto Thyroiditis.

CONTEXT: Preconception optimization of thyroid function in women with Hashimoto thyroiditis (HT) is highly recommended to prevent/reduce the risk of thyroid insufficiency at early gestation. OBJECTIVE: This work aimed to evaluate the prevalence of first-trimester thyroid insufficiency in HT women with preconception thyrotropin (T0-TSH) values consistently less than or equal to 2.5 mIU/L with or without levothyroxine (LT4) treatment, and to calculate T0-TSH cutoffs that best preconceptionally identified HT women requiring first-trimester LT4 adjustment/prescription. METHODS: Serum TSH was obtained at 4- to 6-week intervals from 260 HT pregnant women (122 on LT4 [Hypo-HT]; 138 euthyroid without LT4 [Eu-HT]), prospectively followed from preconception up to pregnancy term. Receiver operating characteristic (ROC) curves were plotted to identify T0-TSH cutoffs best predicting first-trimester TSH levels greater than 2.5 mIU/L (diagnostic criterion [DC] 1) and greater than 4.0 mIU/L (DC 2). RESULTS: At first trimester, TSH was greater than 2.5 mIU/L in approximately 30% of both Hypo-HT and Eu-HT women, and greater than 4.0 mIU/L in 19.7% Hypo-HT and 10.1% Eu-HT women (P = .038). The optimal ROC-based T0-TSH cutoffs found were 1.24 mIU/L/1.74 mIU/L in Hypo-HT, and 1.73 mIU/L/2.07 mIU/L in Eu-HT women, for DC 1 and DC 2, respectively. T0-TSH values exceeding these cutoffs resulted in a statistically significantly increased risk of first-trimester thyroid insufficiency (odds ratio [OR] [95% CI)] 15.92 [5.06-50.15] and 16.68 [5.13-54.24] in Hypo-HT; 16.14 [6.47-40.30] and 17.36 [4.30-70.08] in Eu-HT women, for DC 1 and DC 2, respectively). CONCLUSION: The preconception TSH cutoffs that guaranteed a first-trimester TSH less than 2.5 mU/L in hypothyroid- and euthyroid-HT women were, respectively, almost 50% (1.24 mU/L) and 30% (1.73 mU/L) lower than this gestational target, and 1.74 mU/L and 2.07 mU/L in hypothyroid- and euthyroid-HT women, respectively, for a gestational target of 4.0 mU/L.

Recruitment in randomized clinical trials: The MeMeMe experience.

INTRODUCTION: Recruitment is essential for the success of clinical trials. We are conducting a randomized clinical trial to test the effect of a Mediterranean dietary intervention with or without 1700 mg/day of metformin for the prevention of age-related chronic diseases, the MeMeMe trial (Trial registration number: EudraCT number: 2012-005427-32 ClinicalTrials.gov ID: NCT02960711). MeMeMe recruiting experience, highlighting strengths, limitations encountered and results is reported. PATIENTS AND METHODS: Statistical analysis focused on the reasons for withdrawal according to the recruitment method ("active" versus "passive" criterion) and the time of withdrawal. Logistic regression models were used to explore the associations between the risk of withdrawal and sex, recruitment method, randomization arm, and with markers of compliance to the intervention, such as one-year change in body weight. RESULTS: Out of 2035 volunteers, 660 (32.4%) were recruited "actively" and 1375 (67.6%) "passively". Among people who dropped out of the trial after randomization, there were 19.5% for the "active" and 22.0% for the "passive" method (p = 0.28). The risk of withdrawal was significantly higher in women (OR:1.91; 95% CI:1.17-3.12; p = 0.01), in volunteers older at recruitment (OR:1.25; 95% CI:1.07-1.45; p = 0.004), and in those with a higher BMI at baseline (OR:1.23; 95% CI:1.07-1.43; p = 0.004). Volunteers who lost at least 2 kg (the median weight change) in the first year of intervention were significantly less (53%) likely to withdraw from the trial (OR:0.48; 95% CI:0.30-0.75; p = 0.001). CONCLUSION: Our findings suggest that the "passive" recruitment method was more effective than the "active" one to advance recruitment. The benefits of "passive" recruitment hardly outweighed the drawbacks. TRIAL REGISTRATION: Trial registration number: EudraCT number: 2012-005427-32. ClinicalTrials.gov ID: NCT02960711.

Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients.

Introduction: Artificial Intelligence (AI) methods are being increasingly investigated as a means to generate predictive models applicable in the clinical practice. In this study, we developed a model to predict the efficacy of immunotherapy (IO) in patients with advanced non-small cell lung cancer (NSCLC) using eXplainable AI (XAI) Machine Learning (ML) methods. Methods: We prospectively collected real-world data from patients with an advanced NSCLC condition receiving immune-checkpoint inhibitors (ICIs) either as a single agent or in combination with chemotherapy. With regards to six different outcomes - Disease Control Rate (DCR), Objective Response Rate (ORR), 6 and 24-month Overall Survival (OS6 and OS24), 3-months Progression-Free Survival (PFS3) and Time to Treatment Failure (TTF3) - we evaluated five different classification ML models: CatBoost (CB), Logistic Regression (LR), Neural Network (NN), Random Forest (RF) and Support Vector Machine (SVM). We used the Shapley Additive Explanation (SHAP) values to explain model predictions. Results: Of 480 patients included in the study 407 received immunotherapy and 73 chemo- and immunotherapy. From all the ML models, CB performed the best for OS6 and TTF3, (accuracy 0.83 and 0.81, respectively). CB and LR reached accuracy of 0.75 and 0.73 for the outcome DCR. SHAP for CB demonstrated that the feature that strongly influences models' prediction for all three outcomes was Neutrophil to Lymphocyte Ratio (NLR). Performance Status (ECOG-PS) was an important feature for the outcomes OS6 and TTF3, while PD-L1, Line of IO and chemo-immunotherapy appeared to be more important in predicting DCR. Conclusions: In this study we developed a ML algorithm based on real-world data, explained by SHAP techniques, and able to accurately predict the efficacy of immunotherapy in sets of NSCLC patients.

Nutritional iodine status and obesity.

Iodine is an essential component of the thyroid hormones, thyroxine and triiodothyronine. Its availability strictly depends on iodine content of foods, which may vary from very low to very high. Inadequate iodine intake (deficiency or excess) may affect thyroid function resulting in hypothyroidism or hyperthyroidism. Based on median urinary iodine concentrations, epidemiological criteria have been established for the categorization and monitoring of nutritional iodine status of a population (or subgroups of populations). Additional methods for iodine intake assessment include measurement of thyroid size (by thyroid palpation or ultrasonography) and of biochemical parameters, such as neonatal thyroid stimulating hormone, thyroglobulin and thyroid hormones.Recent studies carried out in overweight/obese children and adults provide evidence that body mass index (BMI) may significantly influence the above indicators, thus theoretically affecting the epidemiological evaluation of nutritional iodine status in populations.In this short review, we analyze current knowledge on the effects of overweight and obesity on indicators of adequacy and monitoring of iodine status, namely urinary iodine excretion and thyroid volume and echogenicity.Data on urinary iodine excretion in overweight/obese children are divergent, as both increased and reduced levels have been reported in overweight/obese children compared to normal-weight controls.Whether gastrointestinal surgery may affect iodine absorption and lead to iodine deficiency in patients undergoing bariatric surgery has been evaluated in a limited number of studies, which excluded iodine deficiency, thus suggesting that supplements usually recommended after bariatric surgery do not need to include iodine.Albeit limited, evidence on thyroid volume and obesity is consistent with a direct relationship between thyroid volume and BMI, irrespective of nutritional iodine status. Finally, a higher frequency of thyroid hypoechoic pattern has been described in overweight/obese children. This finding has been recently related to an increased adipocyte infiltration and thyroid parenchyma imbibition mediated by inflammatory cytokines and should be considered when the frequency of thyroid hypoechoic pattern is used as non-invasive marker to indirectly assess thyroid autoimmunity in monitoring Universal Salt Iodization programs. Further studies, specifically addressing the role of schoolchildren body mass index as a factor potentially influencing iodine intake indicators are needed.

Optical behaviors, surface treatment, adhesion, and clinical indications of zirconia-reinforced lithium silicate (ZLS): A narrative review.

OBJECTIVES: The present narrative review was focused on the optical properties, surface treatment, adhesion, and clinical indications of zirconia-reinforced lithium silicate ceramics (ZLS) for Computer-aided design / Computer-aided manufacturing (CAD/CAM) technologies. DATA/SOURCES: A literature search was performed by 3 calibrated independent researchers on PubMed, Scopus, Embase, Google Scholar, Dynamed, and Open Grey. The criteria for inclusion were: 1) papers addressing at least one of the following variables about ZLS: optical properties, surface treatment, adhesion, and clinical indications; 2) in vitro, in silico, or in vivo studies; 3) case reports; 4) systematic reviews. The exclusion criteria were: 1) animal studies; 2) non-dental studies; 3) studies only focusing on ZLS used in the heat-pressed process. STUDY SELECTION: 98 records among in vitro studies and case reports were included. CONCLUSIONS: Despite the promising microstructure characteristics of ZLS, increased translucency compared to lithium disilicate ceramics (LS2) was not proven, but acceptable color changes and stability were reported. Mechanical polishing was the most effective method to reduce surface roughness. Moreover, machinability and handling of ZLS resulted harder than LS2. Conventional acid etching procedures seemed effective in conditioning ZLS surface, but no protocol has been established yet. Besides, silane-coupling and dual-curing resin cements were recommended. CLINICAL SIGNIFICANCE: ZLSs can be used for anterior and posterior fixed single-unit CAD/CAM restorations onto both natural teeth and implants, but do not seem to represent a viable treatment option for endocrowns onto posterior teeth or fixed dental prostheses.

Adherence to the 2018 WCRF/AICR recommendations and sleep behaviour in people with metabolic syndrome.

OBJECTIVES: to investigate the association between the adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations and the prevalence of parameters of sleep quality and quantity in people with metabolic syndrome (MS). DESIGN: cross-sectional study. SETTING AND PARTICIPANTS: 126 people with MS included in a randomized controlled trial of Mediterranean diet and metformin for the primary prevention of age-related chronic diseases (Me.Me.Me. study) wore for one week an actigraph called Actiwatch to assess restful sleep parameters (sleep efficiency - SE, actual sleep time - AST, immobile time - IT) and fragmented sleep parameters (moving time - MT, movement and fragmentation index - MFI, sleep latency - SL). At the baseline visit, each participants completed a 24-hour food frequency diary listing what he/she ate the previous day, and the International Physical Activity Questionnaire. These questionnaires were used to build up a score for adherence to seven relevant 2018 WCRF/AICR recommendations. MAIN OUTCOME MEASURES: the prevalence ratios (PRs) and 95% confidence intervals (CIs) of sleep parameters associated with each recommendation and with the number of met recommendations were calculated using a binomial regression model. RESULTS: the PRs for SE>=85% and IT>=84% increased with the number of met recommendations. Meeting 5-7 recommendations compared to 0-2 was associated with a better SE (PR 3.24 for SE>=85%; p=0.03) and IT (PR 1.68 for IT>=84%; p=0.04). The PRs for MFI>=34.5 and SL>=18 minutes decreased with the number of met recommendations. Meeting 5-7 recommendations compared to 0-2 was associated with a 46% lower prevalence of MFI (p=0.02) and 40% lower prevalence of SL (p=0.04). CONCLUSIONS: the findings of this paper suggest that the prevalence of better sleep quality in people with MS might be associated with closer adherence to 2018 WCRF/AICR recommendations.

Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation.

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

Fourteen-year evaluation of posterior zirconia-based three-unit fixed dental prostheses: A Prospective clinical study of all ceramic prosthesis.

OBJECTIVES: the purpose of the present prospective trial was to evaluate the clinical performance of posterior 3-unit zirconia-based fixed dental prostheses (FDPs) after 14 years of clinical function. METHODS: thirty-seven patients needing to replace either premolars or molars were involved and 48 FDPs were fabricated (Procera Zirconia, Nobel Biocare AB). Frameworks with a9 mm2 cross section of the connectors and 0.6 mm minimum thickness of the retainers were made by means of Procera Forte CAD-CAM System (Nobel Biocare AB). The patients were recalled after 6 and 12 months and then yearly up to a total follow-up of 14 years. Two independent survival curves for patients wearing 1 or 2 FDPs were calculated by means of Kaplan-Meier analysis and a log-rank test was performed in order to compare these curves. The United States Public Health Service criteria were used to examine technical and esthetic outcomes. The biological examination was performed evaluating plaque control, pocket depth, attachment level, bleeding on probing at both abutments and contralateral teeth and evaluated by means of the Wilcoxon test (p < 0.05) between the baseline and the 14-year follow-up. RESULTS: descriptive statistics resulted in 91 % and 99 % cumulative survival rates for patients wearing 1 and 2 FDPs, respectively. There were no significant differences in periodontal parameters between control and test teeth. Both function and esthetic results were successful for FDPs over a 14-year follow-up period. CONCLUSIONS: the results of this prospective clinical study confirmed the effectiveness of zirconia as a clinical option to fabricate short-span posterior FDPs. CLINICAL SIGNIFICANCE: within the limitations of the present prospective clinical study, zirconia-based three-unit fixed dental prostheses perform satisfactorily on long term, in posterior areas and in patients with standard biomechanical conditions.

Accuracy of Three Impression Materials on the Totally Edentulous Maxilla: In Vitro/In Silico Comparative Analysis.

BACKGROUND: This study was aimed at comparing the accuracy of impressions of a reference typodont (RT) reproducing a totally edentulous maxilla made with three impression materials: polysulfide, polyether, and polyvinyl-siloxane. METHODS: The RT was scanned using a desktop scanner, obtaining a reference scan. Ten impressions for each of the three tested materials were made using a mechanical device with a standardized and consistent modality. A laboratory scanner performed the digitization of each impression. We produced digital models by processing "in reverse" the scans of the physical impressions using a dedicated software, obtaining three groups (n = 10), respectively. The groups were titled: "polysulfide," "polyvinyl-siloxane," and "polyether." The scans in .stl format were imported into Geomagic Control X and then compared to RT to evaluate the accuracy of each scan by calculating trueness and precision in µm. Recorded data were subjected to descriptive statistics. RESULTS: Trueness (arithmetic proximity) values (95%CI) were: polysulfide = 249.9 (121.3-378.5), polyvinyl-siloxane = 216.8 (123.1-310.6), polyether = 291.1 (219.9-362.3). Precision values (95% CI) were: polysulfide = 261.9 (108.8-415), polyvinyl-siloxane = 209.4 (111.9-306.8), polyether = 283 (227.9-338.1). Statistically significant differences were not detected between the means of the experimental groups, both for trueness and precision. CONCLUSIONS: The accuracy of the scans obtained from polyvinyl-siloxane, polysulfide, and polyether impressions can be considered comparable in a fully edentulous maxilla.

Current status on lithium disilicate and zirconia: a narrative review.

BACKGROUND: The introduction of the new generation of particle-filled and high strength ceramics, hybrid composites and technopolymers in the last decade has offered an extensive palette of dental materials broadening the clinical indications in fixed prosthodontics, in the light of minimally invasive dentistry dictates. Moreover, last years have seen a dramatic increase in the patients' demand for non-metallic materials, sometimes induced by metal-phobia or alleged allergies. Therefore, the attention of scientific research has been progressively focusing on such materials, particularly on lithium disilicate and zirconia, in order to shed light on properties, indications and limitations of the new protagonists of the prosthetic scene. METHODS: This article is aimed at providing a narrative review regarding the state-of-the-art in the field of these popular ceramic materials, as to their physical-chemical, mechanical and optical properties, as well as to the proper dental applications, by means of scientific literature analysis and with reference to the authors' clinical experience. RESULTS: A huge amount of data, sometimes conflicting, is available today. Both in vitro and in vivo studies pointed out the outstanding peculiarities of lithium disilicate and zirconia: unparalleled optical and esthetic properties, together with high biocompatibility, high mechanical resistance, reduced thickness and favorable wear behavior have been increasingly orientating the clinicians' choice toward such ceramics. CONCLUSIONS: The noticeable properties and versatility make lithium disilicate and zirconia materials of choice for modern prosthetic dentistry, requiring high esthetic and mechanical performances combined with a minimal invasive approach, so that the utilization of such metal-free ceramics has become more and more widespread over time.

Hyperthyroidism in the pregnant woman: Maternal and fetal aspects.

Hyperthyroidism during pregnancy is uncommon. Nonetheless, prompt identification and adequate management of hyperthyroidism in a pregnant woman is essential, because uncontrolled thyrotoxicosis significantly increases the risk of maternal and fetal complications. Also, fetal prognosis may be affected by the transplacental passage of maternal thyroid stimulating antibodies or thyrostatic agents, both of which may disrupt fetal thyroid function. Birth defects have been reported in association with the use of antithyroid drugs during early pregnancy. Although rarely, offspring of mothers with Graves' disease may develop fetal/neonatal hyperthyroidism, the management of which requires a close collaboration between endocrinologists, obstetricians, and neonatologists. Because of the above considerations, the management of pregnant and lactating women with hyperthyroidism requires special care, bearing in mind that both maternal thyroid excess per se and related treatments may adversely affect the newborn's health. In this review we discuss the diagnosis and management of hyperthyroidism in pregnancy, along with the impact of thyrotoxicosis and medications on fetal outcome.

A management system for randomized clinical trials: A novel way to supply medication.

BACKGROUND: Randomized controlled clinical trials require management effort, involving huge organizational, economic and informatics investments. Information technology offers opportunities to approach clinical trial methodology in new ways. However, there are only a few reports of computerized data and drug management systems. OBJECTIVE: This paper describes a novel software created specifically for the management of a randomized trial of diet and metformin in people with metabolic syndrome (the Me.Me.Me. trial). METHODS: Me.Me.Me. is an ongoing phase III randomized controlled trial in healthy people with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin can prevent age-related chronic non-communicable diseases. To manage all the phases of the trial, we created a software which is a state pattern machine, user friendly, web-based, able to maintain the correct balance between randomization groups, and structured in various levels of security in order to guarantee the participant's privacy and compliance with the study protocol. The software achieves budget savings: drug management is not based on patients' packs, but on the actual need for drugs according to each participant's "state", with strict guidelines for the handling and supply of medication. RESULTS: The trial is ongoing and recruitment will close on August 31, 2018. To date, 11737 bottles of metformin/placebo have been dispensed to 1054 randomized participants, with drug savings of 29.5%. CONCLUSIONS: A software which takes into account the "state" of participant might be a powerful resource for developing and managing clinical trials, helping avoid poor treatment allocation, and wastage of drugs and money. ME.ME.ME. TRIAL: EUDRACT no. 2012-005427-32. ClinicalTrials.gov Identifier: NCT02960711.

Nodular Thyroid Disease in the Era of Precision Medicine.

Management of thyroid nodules in the era of precision medicine is continuously changing. Neck ultrasound plays a pivotal role in the diagnosis and several ultrasound stratification systems have been proposed in order to predict malignancy and help clinicians in therapeutic and follow-up decision. Ultrasound elastosonography is another powerful diagnostic technique and can be an added value to stratify the risk of malignancy of thyroid nodules. Moreover, the development of new techniques in the era of "Deep Learning," has led to a creation of machine-learning algorithms based on ultrasound examinations that showed similar accuracy to that obtained by expert radiologists. Despite new technologies in thyroid imaging, diagnostic surgery in 50-70% of patients with indeterminate cytology is still performed. Molecular tests can increase accuracy in diagnosis when performed on "indeterminate" nodules. However, the more updated tools that can be used to this purpose in order to "rule out" (Afirma GSC) or "rule in" (Thyroseq v3) malignancy, have a main limitation: the high costs. In the last years various image-guided procedures have been proposed as alternative and less invasive approaches to surgery for symptomatic thyroid nodules. These minimally invasive techniques (laser and radio-frequency ablation, high intensity focused ultrasound and percutaneous microwave ablation) results in nodule shrinkage and improvement of local symptoms, with a lower risk of complications and minor costs compared to surgery. Finally, ultrasound-guided ablation therapy was introduced with promising results as a feasible treatment for low-risk papillary thyroid microcarcinoma or cervical lymph node metastases.

A randomized controlled trial of Mediterranean diet and metformin to prevent age-related diseases in people with metabolic syndrome.

PURPOSE: Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD. We designed a phase III randomized controlled trial (the Me.Me.Me trial) to evaluate the effect of a comprehensive lifestyle intervention (including moderate physical activity and a Mediterranean-macrobiotic diet) and the effect of treatment with metformin in the prevention of ArCDs in healthy people with MetS. This report describes the scientific protocol of this trial. METHODS: The design of the study is 2 × 2 factorial with 2,000 volunteers to be randomized into 4 equal groups of 500 each, which are allocated to the following treatments: metformin (1,700 mg/day) + active lifestyle intervention, placebo + active lifestyle intervention, metformin (1,700 mg/day) alone, and placebo alone. The metformin/placebo component of the study is double blind. The study is planned for a term of 5 years. RESULTS: The Me.Me.Me. trial is ongoing and recruitment of participants is underway. No patient has completed the 5 years of follow-up. CONCLUSIONS: We believe that the results of the trial will clarify the importance of lifestyle for primary prevention and the role of metformin as a potential chemopreventive agent. The trial is registred on ClinicalTrials.gov with the identification NCT02960711.

Sugar and mineral enriched fraction from olive mill wastewater for promising cosmeceutical application: characterization, in vitro and in vivo studies.

Nowadays, agro-food by-products represent a potential low-cost source of biologically active ingredients which have been paid significant attention as nutraceuticals, medicine, food and cosmetics. In a previous study we evaluated the total sugars, metals and polyphenols of olive mill wastewater (OMWW) from a Cerasuola olive cultivar. In the present work we selectively recovered a sugar and mineral enriched fraction (SMEF) from Cerasuola OMWW by a green adsorption/desorption process. The SMEF was mainly found to be composed of monosaccharides and potassium by HPLC-ELSD and ICP-MS. The in vitro cytotoxicity on human fibroblasts, at different concentrations of the fraction, was investigated by MTT and comet assays. In addition, intracellular reactive oxygen species (ROS) production, apoptosis and cell morphological changes were examined. The physical stability of a formulation containing the SMEF (1% w/w) and its in vivo skin effects were also assessed.Our results highlighted that the SMEF showed a toxic effect at higher concentrations (i.e. cell viability reduction, DNA fragmentation and morphological alterations) well correlated with high ROS levels. Conversely, at low concentrations (0.5% and 1% w/w), no significant changes were observed. For the first time, through stability studies and in vivo tests, we also demonstrated that the SMEF formulation is stable and safe for topical application, since skin hydration improvement without negative effects was observed after 7 days of its use. Therefore, the SMEF has great potential to be used for cosmeceutical applications.

Female Reproductive Factors and Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases.

Complications of endodontically treated teeth restored with fiber posts and single crowns or fixed dental prostheses-a systematic review.

OBJECTIVE: The present systematic review aimed at assessing data from the literature on endodontic and prosthetic complications in endodontically treated teeth restored with fiber posts and single crowns (SCs) or fixed dental prostheses (FDPs). MATERIALS AND METHODS: Available randomized controlled clinical trials evaluating endodontic and prosthetic complications in the teeth treated with fiber posts and restored with different prosthetic restorations were reviewed. PubMed, Evidence-Based Dentistry, BMJ Clinical Evidence, Embase, DynaMed, and gray literature restricted to scientific literature were analyzed; also, manual researches were performed. English language and time filters (from 1990 to 2015) were used. RESULTS: The database search produced 4230 records, many of which were duplicates. The manual research did not produce any other relevant article. After duplications were removed, all the selected databases produced 3670 records. Reading titles and abstracts, two independent reviewers excluded 3664 reports. The full-texts of the remaining six reports were read. Only four studies met the inclusion criteria and were included in this systematic review. CONCLUSIONS: The most frequently reported failures in the available studies were as follows: fiber post debonding, loss of retention of single crowns, and marginal gaps. Less frequently, chippings and fractures were recorded in SCs. No studies about complications related to FDPs were found. CLINICAL RELEVANCE: A correlation between the failure rates of fiber posts and the type of prosthetic restorations just like SCs and FDPs cannot be found to date. Further randomized controlled clinical studies are required to achieve evidence-based conclusions, particularly about the use of fiber posts with FDPs.

Fasting blood glucose and long-term prognosis of non-metastatic breast cancer: a cohort study.

High circulating glucose has been associated with increased risk of breast cancer (BC). There may also be a link between serum glucose and prognosis in women treated for BC. We assessed the effect of peridiagnostic fasting blood glucose and body mass index (BMI) on long-term BC prognosis. We retrospectively investigated 1,261 women diagnosed and treated for stage I-III BC at the National Cancer Institute, Milan, in 1996, 1999 and 2000. Data on blood tests and follow-up were obtained by linking electronic archives, with follow-up to end of 2009. Multivariate Cox modelling estimated hazard ratios (HR) with 95 % confidence intervals (CI) for distant metastasis, recurrence and death (all causes) in relation to categorized peridiagnostic fasting blood glucose and BMI. Mediation analysis investigated whether blood glucose mediated the BMI-breast cancer prognosis association. The risks of distant metastasis were significantly higher for all other quintiles compared to the lowest glucose quintile (reference <87 mg/dL) (respective HRs: 1.99 95 % CI 1.23-3.24, 1.85 95 % CI 1.14-3.0, 1.73 95 % CI 1.07-2.8, and 1.91 95 % CI 1.15-3.17). The risk of recurrence was significantly higher for all other glucose quintiles compared to the first. The risk of death was significantly higher than reference in the second, fourth and fifth quintiles. Women with BMI ≥ 25 kg/m(2) had significantly greater risks of recurrence and distant metastasis than those with BMI < 25 kg/m(2), irrespective of blood glucose. The increased risks remained invariant over a median follow-up of 9.5 years. Mediation analysis indicated that glucose and BMI had independent effects on BC prognosis. Peridiagnostic high fasting glucose and obesity predict worsened short- and long-term outcomes in BC patients. Maintaining healthy blood glucose levels and normal weight may improve prognosis.