A post-irradiation-induced replication stress promotes RET proto-oncogene breakage.

OBJECTIVE: Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites - chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether RET and CCDC6 exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells. METHODS: We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the RET and CCDC6 genes break following irradiation. RESULTS: Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the RET gene. We discovered that both the RET and CCDC6 genes undergo late replication in thyroid cells. However, only RET's replication rate is notably delayed after irradiation. CONCLUSION: The findings suggest that post-irradiation in the RET gene causes a breakage in the replication fork, which could potentially invade another genomic area, including CCDC6. As a result, this could greatly contribute to the high prevalence of chromosomal RET/PTC rearrangements seen in patients exposed to external radiation.

Increased COVID-19 mortality in patients with schizophrenia: A retrospective study in Brazil.

The risk that COVID-19 poses for mortality risk in individuals with schizophrenia in low- and middle-income countries has only been the subject of a few studies. In this retrospective study, we examined the standardized mortality ratio (SMR), by age group and sex, in a cohort of patients diagnosed with schizophrenia (n = 20,417), with second-generation antipsychotics, in a South Brazilian State database (Paraná-Brazil). We performed a linkage with the Brazilian Mortality Information System database between 2020 and 2021. We also assessed in a logistic regression how clozapine could affect COVID-19 mortality controlling by sex, age, and presence of obesity. A secondary analysis was to compare mortality with SMR due to COVID-19 in individuals with and without obesity. Compared to the State population (8,850,682 individuals), those with schizophrenia had more than two times greater risk of dying from COVID-19 (SMR = 2.21, 95 % CI: 1.90-2.55). Between the ages of 16 and 29, their risk is more than ten times higher than the state population (SMR = 10.18, 95 % CI: 4.73-19.33). Obesity showed an almost twofold risk of dying from COVID-19 in the patient's group (OR = 1.89, 95 % CI: 1.39-2.57). Clozapine was not found as a protector or a risk factor for COVID-19 mortality. In Brazil, a middle-income nation, people with schizophrenia are more likely to die prematurely from COVID-19. The burden of schizophrenia is higher in younger and in patients with obesity.

Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs.

Background: CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness. Methods: We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%. Findings: 1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases. Interpretation: Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination. Funding: Research supported by Sanofi.

Female rats present higher oxidative damage and inflammation during goitrogenesis.

Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1ß, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.

Monounsaturated fat-rich diet reduces body adiposity in women with obesity, but does not influence energy expenditure and substrate oxidation: a parallel randomized controlled clinical trial.

BACKGROUND: Obesity is an important and growing health problem whose treatment involves dietary changes. In this context, studying the role of macronutrients in weight loss is required in order to understand which strategies may be applied for weight loss. We aimed to evaluate the effects of diets rich in polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on resting energy expenditure (REE), substrate oxidation, and weight loss in women with obesity. METHODS: Randomized, controlled, single blind, parallel-group clinical trial was conducted for 60 days. Participants (n = 32) were divided into three groups: G1= normocaloric PUFAs-rich diet (12% of total energy expenditure (TEE), 10% of n-6 and up to 2% of n-3); G2= normocaloric MUFAs-rich diet (15-20% TEE); and G3= maintenance of the usual diet. Anthropometric and metabolic variables (REE and substrate oxidation by indirect calorimetry) were evaluated. RESULTS: G2 decreased body weight (-1.92 ± 1.99 kg, P = 0.02), body mass index (BMI) (-0.69 ± 0.70 kg/m2; P = 0.02), waist circumference (WC) (-1.91 ± 1.82 cm; P = 0.02), and body fat (-1.14 ± 1.53 kg; P = 0.04). CONCLUSION: MUFAs-rich diet reduces body weight, BMI, body fat, and WC. CLINICAL TRIALS: NCT02656940. CLINICAL TRIAL REGISTRATION: Clinical Trials: NCT02656940.

Impact of Bariatric Surgery on Thyroid Morphology and Thyroid Function.

INTRODUCTION: Few studies have evaluated the impact of bariatric surgery (BS) on thyroid function and morphology, and how it correlates to inflammatory and metabolic markers. We aimed to evaluate all those parameters together. METHODS: A longitudinal study included 70 patients with severe obesity. The bariatric group (BG) enrolled 40 patients who underwent BS, and the control group (CG) enrolled 30 patients who did not undergo BS. Both were submitted (pre- and 2nd-year) to thyroid ultrasound and laboratory analyses to determine the levels of thyroid hormones, inflammatory, and metabolic markers. RESULTS: Thyroid volume (TV) decreased after BS (-1.5 cm3), differing significantly from the CG (+0.6 cm3; p = 0.003). ΔTV was independently and positively correlated with ΔHOMA-IR (0.41 (0.11/7.16) p = 0.007) and ΔIL6 (0.02 (0.01/0.3) p = 0.016). A nonsignificant correlation between ΔTV and ΔBMI was detected (0.38 (-0.01/0.09) p = 0.152). We also observed a negative correlation between ΔTV and ΔTSH (-2.03 (-2.87/-1.19) p = 0.000) and ΔT3/T4 ratio (-0.06 (-0.09/-0.02) p = 0.001). TSH had a nonsignificant reduction with BS (-0.3872 vs. -0.2483 p = 0.128). The conversion of T4 to T3 had a significant increase after BS, as demonstrated by the T3/T4 ratio (+5.16 p = 0.01). Despite an increase in the prevalence of thyroid nodules in the BG, it was not statistically significant (p = 0.340). CONCLUSION: BS was associated with a reduction in TV and a nonstatistically significant reduction in TSH. The variations in TV were related to the metabolic markers and inflammatory changes. An increase in the conversion of T4 to T3 with BS was detected, possibly related to inflammatory improvement.

Quercetin improves white adipose tissue redox homeostasis in ovariectomized rats.

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS - 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) - via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

Safety Assessment of the CP4 EPSPS and NPTII Proteins in Eucalyptus.

Glyphosate herbicide treatment is essential to sustainable Eucalyptus plantation management in Brazil. Eucalyptus is highly sensitive to glyphosate, and Suzano/FuturaGene has genetically modified eucalyptus to tolerate glyphosate, with the aim of both protecting eucalyptus trees from glyphosate application damage and improving weed management. This study presents the biosafety results of the glyphosate-tolerant eucalyptus event 751K032, which expresses the selection marker neomycin phosphotransferase II (NPTII) enzyme and CP4-EPSPS, a glyphosate-tolerant variant of plant 5-enolpyruvyl-shikimate-3-phosphate synthase enzyme. The transgenic genetically modified (GM) event 751K032 behaved in the plantations like conventional non-transgenic eucalyptus clone, FGN-K, and had no effects on arthropods and soil microorganisms. The engineered NPTII and CP4 EPSPS proteins were heat-labile, readily digestible, and according to the bioinformatics analyses, unlikely to cause an allergenic or toxic reaction in humans or animals. This assessment of the biosafety of the glyphosate-tolerant eucalyptus event 751K032 concludes that it is safe to be used for wood production.

Protective effect of Chromobacterium violaceum and violacein against bone resorption by periodontitis.

OBJECTIVES: The aim of this study was to evaluate the potential protective effect of Chromobacterium violaceum and violacein against periodontitis, in experimental models. MATERIALS AND METHODS: A double-blind experimental study on the exposure to C. violaceum or violacein in experimentally ligature-induced periodontitis, as preventive factors against alveolar bone loss by periodontitis. Bone resorption was assessed by morphometry. Antibacterial potential of violacein was assessed in an in vitro assay. Its cytotoxicity and genotoxicity were evaluated using the Ames test and SOS Chromotest assay, respectively. RESULTS: The potential of C. violaceum to prevent/limit bone resorption by periodontitis was confirmed. Daily exposure to 106 cells/ml in water intake since birth and only during the first 30 days of life significantly reduced bone loss from periodontitis in teeth with ligature. Violacein extracted from C. violaceum was efficient in inhibiting or limiting bone resorption and had a bactericidal effect against Porphyromonas gingivalis in the in vitro assay. CONCLUSIONS: We conclude that C. violaceum and violacein have the potential to prevent or limit the progression of periodontal diseases, in an experimental model. CLINICAL RELEVANCE: The effect of an environmental microorganism with potential action against bone loss in animal models with ligature-induced periodontitis represents the possibility of understanding the etiopathogenesis of periodontal diseases in populations exposed to C. violaceum and the possibility of new probiotics and antimicrobials. This would imply new preventive and therapeutic possibilities.

Impact of the Fourth Industrial Revolution on clinical pharmaceutical services: A scoping review.

BACKGROUND: Digital technologies are becoming increasingly sophisticated and integrated, but the scope of the Fourth Industrial Revolution (4IR) is wider: technologies and innovations are diffusing faster and more widely. Despite the extensive use of telepharmacy technology by patients and pharmacists, there is an absence of research that examines the use of telepharmacy. OBJECTIVE: To investigate the current evidence concerning the impact of the 4IR on the provision of pharmaceutical services. METHODS: A scoping review based on the PCC (Population, Concept, and Context) mnemonic was conducted in Pubmed, Scopus and Web of Science. Population included pharmacist/clinical pharmaceutical services, the concept referred to the 4IR and the context was open. Electronic searches retrieved 8,694 articles that were screened by titles and abstracts. The search yielded 59 studies that were analyzed in terms of country of focus, publication year, type of publication, main technologies, types of pharmacy services, and the role of the Fourth Industrial Revolution. RESULTS: Most of the included studies were conducted in the United States and were published between 2005 and 2021, with the highest number of publications in the year of 2021. The majority of included articles were observational studies. Technologies addressed in the studies were those within the scope of telepharmacy, and most of the articles discussed more than one pharmaceutical service, with medication therapy management as the most frequent. CONCLUSIONS: The Covid-19 pandemic accelerated the use of technologies, identifying promising niches for pharmacists in the field of Pharmaceutical Care. This should encourage pharmacists to fortify their capacity to adopt new technologies in the provision of pharmaceutical services. The frequent use of various technologies has been demonstrated, which indicates the exigency for further health education actions by the pharmacist.

Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells.

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients' survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain's effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.

Association between exposure to pesticides and allergic diseases in children and adolescents: a systematic review with meta-analysis

Abstract Objective: The study aimed to conduct a systematic review of the literature to verify the association between exposure to pesticides and allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) in children and adolescents. Method: A systematic review and meta-analysis were performed using the PRISMA method with the question "What is the association between exposure to pesticides and allergic diseases in children (asthma, allergic rhinitis, and atopic dermatitis)?" MEDLINE, EMBASE, SciELO, and Cochrane electronic databases were searched throughout the period in the literature up to September 2020. A total of 1296 studies were found, and 24 were selected. Results: Exposure to pesticides showed a two-fold greater risk of developing or exacerbating asthma in children and adolescents (odds ratio [OR] = 2.14 95% confidence interval [CI] 1.26-3.64, p < 0.01). There was no association between exposure to pesticides and the development of allergic rhinitis (OR = 2.73, 95% CI 0.13-57.8, p = 0.52) and atopic dermatitis (OR = 2.19, 95% CI 0.51-9.36, p = 0.29). Conclusions: Exposure to pesticides increases the risk of developing or exacerbating asthma in children and adolescents. There was no evidence of an association between exposure to pesticides and the development of allergic rhinitis and atopic dermatitis in children and adolescents, possibly due to the low number of studies found in this review.

The Joint Initiative for Teaching and Learning on Global Health Challenges and One Health experience on implementing an online collaborative course.

The "Joint Initiative for Teaching and Learning on Global Health Challenges and One Health" piloted the online course "Global Health Challenges and One Health in 2021. The present work documents this experience, lessons learned, and the future outlook of the course. A descriptive study was conducted based on the evaluations performed with the enrolled students and course coordinators. Of 30 enrolled students from graduate programs of six institutions from Brazil, Germany, Mozambique, and Kosovo, two unenrolled, and nine failed for not completing the activities. Therefore, 19 (63%) students completed the course. Some challenges identified were language and technology access barriers, difficulty scheduling group meetings due to different time zones, and high workload per credit in some institutions. Activities in groups conducted synchronously, such as debates, journal clubs, and case studies, were highlighted as those with higher impact in the learning process, having more participation of students when carried in small groups. Some students reported the establishment of research and work partnerships with other participants from partner institutions. The experience reinforces the importance of international exchange to improve collaboration between institutions and the impact of working in small interprofessional groups to develop technical, intercultural, and interdisciplinarity competencies necessary to human resources working with the One Health approach. The success of such international educational initiatives depends on overcoming barriers to implementation, which can be detected in institutional and course levels. Therefore, continuing evaluation of the course and improvements must be performed and involve all participants.

Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases.

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

Exercise Improves Redox Homeostasis and Mitochondrial Function in White Adipose Tissue.

Exercise has beneficial effects on energy balance and also improves metabolic health independently of weight loss. Adipose tissue function is a critical denominator of a healthy metabolism but the adaptation of adipocytes in response to exercise is insufficiently well understood. We have previously shown that one aerobic exercise session was associated with increased expression of antioxidant and cytoprotective genes in white adipose tissue (WAT). In the present study, we evaluate the chronic effects of physical exercise on WAT redox homeostasis and mitochondrial function. Adult male Wistar rats were separated into two groups: a control group that did not exercise and a group that performed running exercise sessions on a treadmill for 30 min, 5 days per week for 9 weeks. Reactive oxygen species (ROS) generation, antioxidant enzyme activities, mitochondrial function, markers of oxidative stress and inflammation, and proteins related to DNA damage response were analyzed. In WAT from the exercise group, we found higher mitochondrial respiration in states I, II, and III of Complex I and Complex II, followed by an increase in ATP production, and the ROS/ATP ratio when compared to tissues from control rats. Regarding redox homeostasis, NADPH oxidase activity, protein carbonylation, and lipid peroxidation levels were lower in WAT from the exercise group when compared to control tissues. Moreover, antioxidant enzymatic activity, reduced glutathione/oxidized glutathione ratio, and total nuclear factor erythroid-2, like-2 (NFE2L2/NRF2) protein levels were higher in the exercise group compared to control. Finally, we found that exercise reduced the phosphorylation levels of H2AX histone (γH2AX), a central protein that contributes to genome stability through the signaling of DNA damage. In conclusion, our results show that chronic exercise modulates redox homeostasis in WAT, improving antioxidant capacity, and mitochondrial function. This hormetic remodeling of adipocyte redox balance points to improved adipocyte health and seems to be directly associated with the beneficial effects of exercise.

Binge eating disorder, frequency of depression, and systemic inflammatory state in individuals with obesity - A cross sectional study

ABSTRACT Objective: Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Materials and methods: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 - Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results: Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling "stuffed", and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusions: Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.

Redox Homeostasis in Thyroid Cancer: Implications in Na+/I- Symporter (NIS) Regulation.

Radioiodine therapy (RAI) is a standard and effective therapeutic approach for differentiated thyroid cancers (DTCs) based on the unique capacity for iodide uptake and accumulation of the thyroid gland through the Na+/I- symporter (NIS). However, around 5-15% of DTC patients may become refractory to radioiodine, which is associated with a worse prognosis. The loss of RAI avidity due to thyroid cancers is attributed to cell dedifferentiation, resulting in NIS repression by transcriptional and post-transcriptional mechanisms. Targeting the signaling pathways potentially involved in this process to induce de novo iodide uptake in refractory tumors is the rationale of "redifferentiation strategies". Oxidative stress (OS) results from the imbalance between ROS production and depuration that favors a pro-oxidative environment, resulting from increased ROS production, decreased antioxidant defenses, or both. NIS expression and function are regulated by the cellular redox state in cancer and non-cancer contexts. In addition, OS has been implicated in thyroid tumorigenesis and thyroid cancer cell dedifferentiation. Here, we review the main aspects of redox homeostasis in thyrocytes and discuss potential ROS-dependent mechanisms involved in NIS repression in thyroid cancer.

Environmentally relevant dose of the endocrine disruptor tributyltin disturbs redox balance in female thyroid gland.

Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERß). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway.

Binge eating disorder, frequency of depression, and systemic inflammatory state in individuals with obesity - A cross sectional study.

Introduction: Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Subjects and methods: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 - Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results: Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling "stuffed", and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusion: Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.

Aggressive nonfunctioning pituitary neuroendocrine tumors.

Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.