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Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.

Abstract Context Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO). Objective This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs). Methods Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components. Results At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment. Conclusion The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.

BackgroundGraves’ orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves’ Orbitopathy (EUGOGO) tertiary referral centres and initial management over time.MethodsProspective observational multicentre study. All new referrals with diagnosis of GO within September–December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012.ResultsBesides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0–350) vs 6 (0–552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027).ConclusionGO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Background Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. Method Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. Results Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. Conclusions LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

The prevalence of pituitary tumors has been a topic of controversy for many years. Autopsy and radiological series show that pituitary incidentalomas may be present in one of six people. Recent epidemiological data suggest that clinically apparent pituitary adenomas have a prevalence of approximately one in 1,000 people in the general population. The disconnect between these two prevalence rates underlines the common clinical quandary of how to manage pituitary incidentalomas, particularly those lacking clinical signs/symptoms or hormonal abnormalities. The natural history of incidentalomas suggests that periodic hormonal, clinical and radiological follow-up is the optimal approach. In the absence of tumor growth or relevant symptoms, screening can be continued intermittently or curtailed based on the clinical judgment of the physician. In the presence of hormonal hypersecretion, the management of pituitary incidentalomas, whether they are micro- or macroadenomas, should follow accepted clinical guidelines. For incidental pituitary macroadenomas without hormonal hypersecretion, clinical management should also include assessments for visual field impairment or hypopituitarism. In such cases, regular radiological and hormonal follow-up is required to identify tumor growth or the appearance of new symptoms. In the presence of tumor growth or new hormonal abnormalities, surgical options should be considered and discussed with the patient.

Our study aimed to examine how care centers for older persons acted and adapted during the COVID-19 pandemic period by considering the opinions of the beneficiaries, employees, and managers of such centers. The research was conducted between February and June 2022, and we used a mixed-methods approach. For the quantitative research, we applied a questionnaire to 430 institutionalized older persons from Timis County, Romania. For the qualitative analysis, we conducted interviews with 31 institutionalized older persons, 7 employees, and 4 managers. Most institutionalized older persons were mainly satisfied with their lives in the care centers. The main difficulties they faced were the impossibility of being close to loved ones and the difficulty of adapting to the living conditions within the center. Additionally, the older persons were satisfied with their interactions with the staff of the care centers. The conducted research provides a view of the lifestyle of older persons in care centers during the pandemic. It highlights their struggles and can be used as a reference point for further improvement of the lifestyle of older persons within care centers.

Gamification is becoming more relevant, especially after the start of the COVID-19 pandemic and quarantine. The purpose of our paper is to analyse the changes which occurred in the effects of gamification on e-learning as a result of the COVID-19 quarantine emergence in the spring of 2020. This paper describes the scientific contributions about the game elements most frequently implemented and their effects on those that use e-learning platforms, as well as the factors that contribute to the development of effective gamification in e-learning before and during the pandemic. Drawing upon the PRISMA framework, a number of 103 articles were identified in two databases: the Web of Science and Scopus. This paper discusses the previous works associated with the corpus of knowledge built around gamification in the past decade. This research shows that before the COVID-19 pandemic, even though many papers were written on gamification in education prior to 2019, there is a trend regarding the multiple mentions of using storylines, challenges, or badges in order to create and maintain competition among users, which in turn may influence and increase the level of social interactions and the coalescence of communities.

The potential bioaccumulation of hazardous transitional heavy metals in components of the aquatic environment (such as water column, sedimentary matter, plants) constitutes one of the concerns in environmental protection engineering. This experimental investigative study used systematic measurements of the presence of selected heavy metals (cadmium, chromium, copper, lead, nickel and zinc) in components of the aquatic environment to give an indication of their availability and their potential bioaccumulation in the perennial wetland plants. Through environmental quality data processing, this study allowed both the assessment of interphase partitioning constants of these metals throughout the analyzed aquatic environment and the estimation of their cumulative toxicity coëfficiënt. The data analysis highlighted the different potential degrees of dangers caused by metals as pollutants and the synergistic way in which they act on the aquatic environment.

Considering the debates regarding population migration from rural areas, the purpose of this study is to analyze socio-economic indicators to identify the main challenges of rural areas in Romania as well as to identify solutions to ensure the development of the Romanian rural environment. Our research aims to present the socioeconomic consequences of the rural population's migration by analyzing indicators such as the population by domicile by residence, the average age of the population by domicile, the flow of internal urban and rural migration, the population activity rate, the employed population per economic activities, and the total average monthly income obtained by a rural person. In addition, at the end of the study, a Pearson correlation was made with the help of the SPSS software, which identified the link between income from agriculture and the number of people working in agriculture. The results obtained indicated that while the number of people employed in agriculture, forestry, and fishing is decreasing, the average total income from agriculture is increasing. On the other hand, the migration of the population from the rural area to the urban area is on average about 82 thousand people and the rural population is in a continuous decrease, while the average age registered in the rural area is higher compared to the average age registered in urban areas.

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development.