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Introduction: Active surveillance (AS) is increasingly recognized as an appropriate strategy for selected patients with papillary thyroid microcarcinomas (PTMC). However, some factors, including physician-related ones, hinder its widespread adoption. Methods: To explore the prevailing barriers and the impact of information on attitudes towards AS implementation, we developed a questionnaire that was completed before and after reading a simple information leaflet by 317 doctors working in different work environments. This leaflet provides information about the overdiagnosis of PTMC, the concept of AS, results of early studies, and main advantages and disadvantages of AS. Results: We observed a greater resistance to AS among male physicians who were more likely to maintain the initial recommendation for surgery or referral to a head and neck surgeon than female physicians (77 % vs. 46 %, p = 0.01), regardless of their medical specialty. Fear of disease progression and of the patient losing follow-up were the main concerns. Reading the educational material significantly increased the number of physicians who endorsed AS as an initial approach to PTMC without risk factors from 14 % to 34 % (p

Abstract Blended Intensive Programmes (BIP’s) represent a valuable tool for gathering knowledge and summarising the latest trends in medicine and dentistry. Blended education has been found, even before the COVID-19 pandemic, to increase the level of education and stimulate effective learning for postgraduate healthcare professionals. Interprofessional education is critical for preparing students to enter the health workforce, where teamwork and collaboration are important competencies. This article outlines the key points of the Blended Intensive Programme’s implementation in dental education organised by Wroclaw Medical University in Poland. BIP involved professors from 12 universities or research institutions from Europe and South America and 28 participants from 8 countries. The course was taught remotely and in person. In addition, it included a visit to the university and practical classes with artificial simulation and practice in dentistry. A structured questionnaire enabled measuring the evaluation of students’ perception of the COVID-19 education before and after the pandemic. The European Region Action Scheme for the Mobility of University Students (ERASMUS) was fundamental to carrying out the BIP with the participation of several countries, allowing the exchange of knowledge, assessing the impact of the pandemic on dental universities, and strengthening international collaborations and the future project of research, education and clinical assistance. We conclude that hybrid teaching programmes broaden the learning spectrum in dental studies by allowing transnational and interdisciplinary approaches that make students aware of the importance of their work within the framework of the general health approach, as this differs from country to country.

Objective To provide contemporary data on cancer mortality rates within the context of incidence in the population with intellectual disabilities.Methods Scotland’s 2011 Census was used to identify adults with intellectual disabilities and controls with records linked to the Scottish Cancer Registry and death certificate data (March 2011–December 2019). The control cohort without intellectual disabilities and/or autism were used for indirect standardisation and calculation of crude incident rates/crude mortality rates, and age–sex standardised incident rate ratios/standardised mortality ratios (SIR/SMR), with 95% CIs.Results Adults with intellectual disabilities were most likely diagnosed cancers of digestive, specifically colorectal (14.2%), lung (9.3%), breast (female 22.9%), body of the uterus (female 9.3%) and male genital organs (male 17.6%). Higher incident cancers included metastatic cancer of unknown primary origin (female SIR=1.70, male SIR=2.08), body of uterus (female SIR=1.63), ovarian (female SIR=1.59), kidney (female SIR=1.85) and testicular (male SIR=2.49). SMRs were higher, regardless of a higher, similar or lower incidence (female SMR=1.34, male SMR=1.07). Excess mortality risk was found for colorectal (total SMR=1.54, male SMR=1.59), kidney (total SMR=2.01 u, female SMR=2.85 u), female genital organs (SMR=2.34 (ovarian SMR=2.86 u, body of uterus SMR=2.11), breast (female SMR=1.58) and metastatic cancer of unknown primary origin (female SMR=2.50 u, male SMR=2.84).Conclusions Adults with intellectual disabilities were more likely to die of cancer than the general population. Reasons for this may include later presentation/diagnosis (so poorer outcomes), poorer treatment/compliance or both. Accessible public health approaches are important for people with intellectual disabilities, and healthcare professionals need to be aware of the different cancer experiences faced by this population.

IntroductionSamples classified as indeterminate correspond to 10-20% of cytologies obtained by fine needle biopsy of thyroid nodules, preventing an adequate distinction between benign and malignant lesions and leading to diagnostic thyroidectomies that often prove unnecessary, as most cases are benign. Furthermore, although the vast majority of patients with differentiated thyroid cancer (DTC) have such a good prognosis that active surveillance is permitted as an initial therapeutic option, relapses are not rare, and a non-negligible number of patients experience poor outcomes. MicroRNAs (miR) emerge as potential biomarkers capable of helping to define more precise management of patients in all these situations.MethodsAiming to investigate the clinical utility of miR-146b-5p in the diagnostic of thyroid nodules and evaluating its prognostic potential in a realworld setting, we studied 89 thyroid nodule samples, correlating miR-146b-5p expression with clinical tools such as the 8th edition from the American Joint Committee on Cancer (AJCC/UICC) and the American Thyroid Association Guideline Stratification Systems for the rate of recurrence (RR).ResultsmiR-146b-5p expression levels distinguished benign from malignant thyroid FNA samples (p< 0.0001). For indeterminate nodules, overexpression of miR-146b-5p with a cut-off of 0.497 was able to diagnose malignancy with a 90% accuracy; specificity=87.5%; sensitivity=100%. An increased expression of miR-146b-5p was associated with greater RR (p=0.015). A cut-off of 2.21 identified cases with more vascular involvement (p=0.013) and a cut-off of 2.420 was associated with a more advanced TNM stage (p-value=0.047).DiscussionWe demonstrated that miR-146b5p expression in FNA samples is able to differentiate benign from malignant indeterminate nodules and is associated with an increased risk of recurrence and mortality, suggesting that this single miRNA may be a useful diagnostic and prognostic marker in the personalized management of DTC patients.

Understanding the complex mechanisms involved in diseases caused by or related to important genetic variants has led to the development of clinically useful biomarkers. However, the increasing number of described variants makes it difficult to identify variants worthy of investigation, and poses challenges to their validation. We combined publicly available datasets and open source robust bioinformatics tools with molecular quantum chemistry methods to investigate the involvement of selectins, important molecules in the cell adhesion process that play a fundamental role in the cancer metastasis process. We applied this strategy to investigate single nucleotide variants (SNPs) in the intronic and UTR regions and missense SNPs with amino acid changes in the SELL, SELP, SELE, and SELPLG genes. We then focused on thyroid cancer, seeking these SNPs potential to identify biomarkers for susceptibility, diagnosis, prognosis, and therapeutic targets. We demonstrated that SELL gene polymorphisms rs2229569, rs1131498, rs4987360, rs4987301 and rs2205849; SELE gene polymorphisms rs1534904 and rs5368; rs3917777, rs2205894 and rs2205893 of SELP gene; and rs7138370, rs7300972 and rs2228315 variants of SELPLG gene may produce important alterations in the DNA structure and consequent changes in the morphology and function of the corresponding proteins. In conclusion, we developed a strategy that may save valuable time and resources in future investigations, as we were able to provide a solid foundation for the selection of selectin gene variants that may become important biomarkers and deserve further investigation in cancer patients. Large-scale clinical studies in different ethnic populations and laboratory experiments are needed to validate our results.

Abstract Background The breastfeeding rates of late preterm infants are lower than both term and extremely preterm infants. To explore the interventions of increasing full breast milk feeding rate of hospitalized late preterm infants on the 7th day after birth (D7) and evaluate the effect of these quality improvement (QI) interventions. Methods The full breast milk feeding (amount of enteral breast milk reached 120ml/kg/d on D7) rate of hospitalized late preterm infants during May 2017 and November 2017 was set as the baseline before intervention, and the specific aim of promoting breast milk feeding was put forward. The Pareto Chart was used to analyze the factors that affect breast milk feeding process, as well as the discussion of multidisciplinary experts. Key drivers were constructed, including informational materials and education about breast milk feeding, consultations and support on optimal breast milk initiation, initiating breast milk expression within one hour after birth, accurate measurement and recording of expressed breast milk, stimulating continuous and effective lactation, proper breast pump selection in and out of hospital and sending and preserving of expressed milk to NICU. Control chart was used to monitor the monthly change of full breast milk feeding rate until the aim was achieved and sustained. Results The baseline of full breast milk feeding rate of late preterm infants was 10%, and the aim of QI was to increase the rate to 60% within a two-year period. Control chart dynamically showed the full breast milk feeding rate increased to 80% with the implementation of the interventions, achieved and made the aim of QI sustained. Conclusion QI interventions including breast milk feeding education, early postpartum breast milk pumping, kangaroo care to stimulate breast milk secretion, and convenient way of transporting breast milk to NICU, could significantly improve the full breast milk feeding rate of hospitalized late preterm infants.

Neonicotinoid seed treatments are commonly used in agricultural production even though their benefit to crop yield and their impact on pollinators, particularly wild bees, remains unclear. Using an on-farm matched pair design in which half of each field was sown with thiamethoxam treated seed and half without, we assessed honey bee and wild bee exposure to pesticides in sunflower fields by analyzing pesticide residues in field soil, sunflower pollen and nectar, pollen-foraging and nectar-foraging honey bees, and a sunflower specialist wild bee (Melissodes agilis). We also quantified the effects of thiamethoxam-treated seed on wild bee biodiversity and crop yield. M. agilis abundance was significantly lower with thiamethoxam treatment and overall wild bee abundance trending lower but was not significantly different. Furthermore, crop yield was significantly lower in plots with thiamethoxam treatment, even though thiamethoxam was only detected at low concentrations in one soil sample (and its primary metabolite, clothianidin, was never detected). Conversely, wild bee richness was significantly higher and diversity was marginally higher with thiamethoxam treatment. Nectar volumes harvested from the nectar-foraging honey bees were also significantly higher with thiamethoxam treatment. Several pesticides that were not used in the sunflower fields were detected in our samples, some of which are known to be deleterious to bee health, highlighting the importance of the landscape scale in the assessment of pesticide exposure for bees. Overall, our results suggest that thiamethoxam seed treatments may negatively impact wild bee pollination services in sunflower. Importantly, this study highlights the advantages of the inclusion of other metrics, such as biodiversity or behavior, in pesticide risk analysis, as pesticide residue analysis, as an independent metric, may erroneously miss the impacts of field realistic pesticide exposure on bees.

Abstract To better understand the relationship among cell adhesion molecules (CAM) and investigate the clinical diagnostic and prognostic application of ICAM-1 (ICAM1), LFA-1 (ITGAL), and L-selectin (SELL) proteins and mRNA corresponding expression in thyroid cancer. Gene expression was evaluated by RT–qPCR, and protein expression was evaluated by immunohistochemistry. We evaluated 275 patients (218 women, 57 men, 48.4 ± 14.5 years old), including 102 benign and 173 malignant nodules. The 143 papillary thyroid carcinoma (PTC) and 30 follicular thyroid carcinoma (FTC) patients were managed according to current guidelines and followed-up for 78.7 ± 54.2 months. Malignant and benign nodules differed concerning mRNA (p = 0.0027) and protein (p = 0.0020 for nuclear) expression of L-selectin and ICAM-1 (mRNA: p = 0.0001 and protein: p = 0.0014) and protein expression of LFA-1 (p = 0.0168), but not mRNA expression of LFA-1 (p = 0.2131). SELL expression was more intense in malignant tumors (p = 0.0027). ICAM1 (p = 0.0064) and ITGAL (p = 0.0244) mRNA expression was higher in tumors with lymphocyte infiltrate. ICAM-1 expression correlated with younger age at diagnosis (p = 0.0312) and smaller tumor size (p = 0.0443). Also, LFA-1 expression correlated with higher age at diagnosis (p = 0.0376) and was more intense at stage III and IV (p = 0.0077). In general, the protein expression of the 3 CAM decreased as the process of cellular dedifferentiation occurred. We suggest that the SELL and ICAM1 genes and L-selectin and LFA-1 protein expression may help confirm malignancy and assist in the histological characterization of follicular patterned lesions, but we were unable to correlate these CAMs with patient outcomes.

ABSTRACT Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.

Introdução: Nosso grupo tem demonstrado evidências da relação entre os herpesvírus e a carcinogênese tireoidiana. O Herpes Simplex Vírus tipo 2 (HSV-2), um dos agentes infecciosos de maior prevalência mundial, tem se destacado nessa associação com o carcinoma diferenciado da tireoide (CDT) já que se aloja em linfonodos cervicais. Objetivo: Comparar a incidência de anticorpos da classe das IgG humanas para HSV-2 em soro de pacientes com nódulos tireoidianos benignos malignos com um grupo controle. Método: Para identificar a soroprevalência da infecção pelo HSV-2 em pacientes com CDT, analisamos a presença de anticorpos anti-HSV 2 utilizando o kit detecção da imunoglobulina G (HerpeSelect® 2 IgG -Focus Diagnostics, EUA) com alta especificidade para HSV-2 em 300 amostras sorológicas, sendo 150 pacientes com nódulos benignos e malignos da tireoide (131 mulheres e 19 homens, 42,34 ± 10,90 anos), onde 65 eram nódulos benignos (48 bócios, 17 AF) e 85 eram nódulos malignos (29 MCPT e 56 CPT); e 150 soros controles (21 homens e 129 mulheres e média de (45,0 ± 11,0 anos). Resultados: A soropositividade para HSV-2 foi observada em 37 (25%) dos pacientes com nódulos tireoidianos e em 32 (21%) dos controles (p = 0,5122). A taxa de soropositividade foi semelhante em pacientes com nódulos tireoidianos benignos (28%) e malignos (22%; p = 0,4522), e entre mulheres (12,2%) e homens (16,5%; p = 0,3415). Conclusão: Embora a soroprevalência de HSV-2 tenda a ser maior nos pacientes com nódulos tireoidianos do que na população sem nódulos, não foi possível correlacionar a presença do HSV-2 com tamanho dos nódulos, tipo histológico ou qualquer característica clínica, ou de evolução dos pacientes. Cálculo de tamanho amostral sugere que necessitamos de mais amostras, pois nosso poder de cálculo ainda é de 43%. Estamos providenciando o aumento da nossa casuística para confirmar possível correlação do HSV-2 com pacientes com nódulos tireoidianos malignos.

The immune response is remodeled with aging in a process called immunosenescence. Some immunologists conceive immunosenescence as an adaptation of immunity to the aged immune-environment rather than a merely collapsed reactivity of immune cells against microbes and tumor cells. Others believe on an uninterrupted activation of the innate immune system with aging, leading to a low grade, sterile and chronic proinflammatory state called inflammaging. For instance, it is possible that chronic infection by cytomegalovirus leads to persistent production of viral load. This phenomenon offers periodic stimuli to the immune system that ultimately contribute to the remodeling of the immune response. If investigating immunosenescence at the cellular level is already a difficult task, considering the population level is much more complex. However, by studying immunosenescence at the population level, we can extract valuable results with viable applications. While studies with animal models allow scientists to deepen their understanding of the mechanisms of immunosenescence, studying large populations can bring practical innovations to medicine and the health system. Many researchers and funders have dedicated themselves to producing methods for the evaluation of immunosenescence on a large scale, aiming to elucidate new mechanisms by which diseases are established in the elderly. The description of how the immune response is remodeled with aging emerges as a new tool to identify the subset of subjects in which unhealthy aging is a matter of time, to help better individualize clinical management and select patients who may benefit. of early interventions. This review focuses on functional assays as valuable methods for measuring the remodeling of the immune response with aging and discuss their clinical impact. We also recall fundamental concepts for understanding the aging process of the immune response. In addition, we highlight future prospects for immunosenescence research.

Endocrine-disrupting and carcinogenic effects of glyphosate have long been suspected, but little is known about the effect of compounds used in real life at different concentrations, neither in normal nor in thyroid tumor cells. As cancer cells may have different sensitivities and the effect of the product containing glyphosate may be different from that produced by the active ingredient alone, including the Acceptable Occupational Exposure Level (AOEL=160µg/L) and the Acceptable Daily Intake (ADI=830µg/L) determined by ANVISA, we used two human thyroid-derived cell lines, Nthy-ori 3-1 (from normal follicular cells) and TPC-1 (from papillary carcinoma), to test 15 different concentrations of Roundup® Original DI. Trypan blue (TB), CCK-8 and BrdU assays were used to evaluate cytotoxicity, metabolic activity and proliferation with 24h and 48h exposures in technical and biological triplicates. TB showed an important toxic effect, especially after 24h of exposure, in both cell lines. The AOEL concentration caused the death of 43% and 50% of the Nthy-ori and TPC-1 cells, respectively, in 24 h, while ADI resulted in 35% and 58% of cell death. After 48h of exposure, AOEL and ADI caused a lower number of dead Nthy-ori (33% and 18%) and TPC-1 (33% and 37%) cells, respectively, suggesting that the toxic effect of the product disappears and/or both strains have repair mechanisms that protect them from longer exposures. On the other hand, the CCK-8 assay showed that small concentrations of Roundup have a proliferative effect: 6.5µg/L increased the number of both Nthy-ori and TPC-1 cells at 24h, and the BrdU assay confirmed the stimulatory effect with a 321% increase in the absorbance of Nthy-ori cells at 48h. The herbicide produced even more frequent increases in the BrdU absorbance of TPC-1 cells, mainly at 24h. We conclude that thyroid cells exposed to Roundup present a nonmonotonic dual dose–response curve. Low concentrations of the pesticide, considered acceptable, cause significant cell death but also have an important proliferative effect, especially on TPC-1 cells. This herbicide, widely used around the world, may play a role in the increased incidence rate of thyroid nodules and cancer that has been observed in recent decades.

ContextAlthough the overt hyperthyroidism treatment during pregnancy is mandatory, unfortunately, few studies have evaluated the impact of treatment on reducing maternal and fetal outcomes.ObjectiveThis study aimed to demonstrate whether treatment to control hyperthyroidism manifested during pregnancy can potentially reduce maternal-fetal effects compared with euthyroid pregnancies through a systematic review with meta-analysis.Data SourceMEDLINE (PubMed), Embase, Cochrane Library Central, LILACS/BIREME until May 2021.Study SelectionStudies that compared, during the gestational period, treated women with hyperthyroidism versus euthyroid women. The following outcomes of this comparison were: pre-eclampsia, abruptio placentae, fetal growth retardation, gestational diabetes, postpartum hemorrhage, low birth weight, stillbirth, spontaneous abortions, premature birth.Data ExtractionTwo independent reviewers extracted data and performed quality assessments. Dichotomous data were analyzed by calculating risk differences (DR) with fixed and random effect models according to the level of heterogeneity.Data SynthesisSeven cohort studies were included. The results of the meta-analysis indicated that there was a lower incidence of preeclampsia (p=0.01), low birth weight (p=0.03), spontaneous abortion (p

Although stressful events are known to trigger Graves’ disease (GD), the mechanisms involved in this process are not well understood. The NR3C1 gene, encoding for the glucocorticoid receptor (GR), presents single nucleotide polymorphisms (SNPs) that are associated with stress-related diseases. To investigate the relationship between NR3C1 SNPs, GD susceptibility, and clinical features, we studied 792 individuals, including 384 patients, among which 209 presented with Graves’ orbitopathy (GO), and 408 paired healthy controls. Stressful life events were evaluated in a subset of 59 patients and 66 controls using the IES-R self-report questionnaire. SNPs rs104893913, rs104893909, and rs104893911 appeared at low frequencies and presented similar profiles in patients and controls. However, variant forms of rs6198 were rarer in GD patients, suggesting a protective effect. Stressful events were more common in patients than controls, and were reported to have clearly occurred immediately before the onset of GD symptoms in 23 cases. However, no association was found between these events and rs6198 genotypes or GD/GO characteristics. We suggest that the NR3C1 rs6198 polymorphism may be an important protective factor against GD, but its relationship with stressful events needs further investigation.