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Importance: Tablet use continues to increase in preschool-aged children. The use of mobile devices has been linked to child emotional dysregulation. However, few studies have been able to show a clear direction of association between child tablet use and the development of self-regulation skills. In addition, few studies have modeled within-person associations over time., Objective: To estimate how child tablet use contributes to expressions of anger and frustration across the ages of 3.5 to 5.5 years at the within-person level. The study team also examined the extent to which associations are bidirectional to clarify the direction of the correlations., Design, Setting, and Participants: This prospective, community-based convenience sample of 315 parents of preschool-aged children from Nova Scotia, Canada, was studied repeatedly at the ages of 3.5 (2020), 4.5 (2021), and 5.5 years (2022) during the COVID-19 pandemic. All analyses were conducted between October 5, 2023, and December 15, 2023., Exposure: Parent-reported tablet use at the ages of 3.5, 4.5, and 5.5 years., Main Outcome and Measures: Parents reported child expressions of anger/frustration at the ages of 3.5, 4.5, and 5.5 years using the Children's Behavior Questionnaire., Results: The sample was equally distributed across child sex (171 were identified by parents as being born boys [54%] and 144 as girls [46%]). Most reported being Canadian (287 [91.0%]) and married (258 [82.0%]). A random-intercept cross-lagged panel model revealed that a 1-SD increase in tablet use at 3.5 years (corresponding to 1.22 hours per day) was associated with a 22% SD scale increase in anger/frustration at age 4.5 years (standardized coefficient = 0.22; 95% CI, 0.01-0.44). A 1 SD scale increase in anger and frustration at 4.5 years was associated with a 22% SD (corresponding to 0.28 hours per day) increase in tablet use at 5.5 years (standardized coefficient = 0.22; 95% CI, 0.01-0.43)., Conclusion and Relevance: In this study, child tablet use at age 3.5 years was associated with more expressions of anger and frustration by the age of 4.5 years. Child proneness to anger/frustration at age 4.5 years was then associated with more use of tablets by age 5.5 years. These results suggest that early-childhood tablet use may contribute to a cycle that is deleterious for emotional regulation.

Introduction: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population., Purpose: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC., Materials and Methods: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up., Results: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs., Conclusions: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent., Methodology/principal Findings: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR., Conclusions/significance: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility., Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI., Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured., Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments., Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

This study aimed to evaluate the physiological and reproductive parameters of Nelore cows under various microclimatic conditions. The experiment was performed in Central Brazil, which has a tropical climate with dry winters and rainy summers. The experimental groups were divided into an area with shading (5.8 trees/ha; n = 42) and an area with little shading (0.4 trees/ha; n = 42). The physiological (heart rate, respiratory rate, rectal temperature, surface body temperature, and vaginal temperature) and reproductive (estrus detection, conception rate, and rate of pregnancy loss) parameters were then assessed. The rectal temperature (p = 0.002); surface body temperature on the flanks, forehead, and shoulder (p < 0.001); and vaginal temperature (p < 0.001) of cows in the group with shading were significantly lower than those of cows in the group without shading. Estrus was higher (p = 0.08) in the shaded group; however, no effect was observed on conception and pregnancy loss rates. In conclusion, shading (5.8 trees/ha) provided better thermal comfort for Nelore animals in the tropical climatic region. However, this did not affect their performance after fixed-time artificial insemination., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: The aim of this study was to analyze HLA alleles in patients with Behçet disease (BD) and their correlation with ophthalmic manifestations (OMs) in a multiethnic Brazilian population., Methods: This case-control study compared 72 BD patients with or without OM who underwent a thorough ophthalmologic evaluation, including best-corrected visual acuity, bino-ophthalmoscopy, and HLA analysis, with 144 matched healthy controls. Fluorescein angiography was also performed in the patients with BD and OM. HLA class I (A, B, and C) and II (DRB1, DQB1, and DQA1) typing were performed using PCR-SSO., Results: Of 72 patients with BD, 42 (58%) had OM. The HLA-B*51 and -A*26 alleles were more frequent in patients with BD than in controls (23.6% vs 14.6% and 12.5% vs 4.3%, respectively), but could not differentiate OM risk. The HLA alleles of BD patients that differentiated those with and without OM were HLA-B*15 (40.5% vs 20.7%; odds ratio [OR], 2.59; p = 0.0059), HLA-C*02 (33.3% vs 13.4%; OR, 3.20; p = 0.0024), and HLA-DQB1*03 (64.3% vs 45.7%, p = 0.017), whereas HLA-A*03 (0.0% vs 13.3%, p = 0.006) and HLA-DRB1*15 (4.8% vs 19.5%; OR, 0.21; p = 0.0121) were protective against OM., Conclusions: In this study of a Brazilian multiethnic BD population, alleles were similar between groups of BD patients with and without OM. We described HLA-B*15, -C*02, and -DQB1*03 as risk factors and -A*03 and -DRB1*15 as protective factors for OM in BD, which could function as biomarkers for predicting disease phenotypes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca 2+ channels (SOCs), Ca 2+ -activated K + channels (IK Ca and BK Ca ), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Figueiredo, Ferreira, Fernandes, Silva, Vasconcelos and Cavalcante.)

Purpose: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS)., Methods: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status., Conclusion: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Western Gondwana amalgamated by collision of continental blocks that did not form prior conjugated margins (extroversion), and by typical Wilson cycles, when continental blocks that rifted away giving birth to new oceans were subsequently re-joined in approximately the same position (introversion). The introverted systems are characterized by the opening of V-shaped basins through rifting and hyperextension of various continental pieces (micro- and ribbon continents) from a former Central African Block. These continental fragments lost substantial parts of their mantle lithosphere and became decratonized while drifting towards the external Goiás-Pharusian ocean. Protracted seafloor spreading and consumption through subduction of the internal and external oceans, respectively, ultimately led to multiple, diachronous collisions with other continental blocks detached from Rodinia (Amazonian, West Africa, Embu, etc.). These collisions pushed the ribbon continents back and closed the introverted basins, squeezing and incorporating the reworked basement tracts between the main colliding blocks and the rigid remainder of the Central African Block (the São Francisco-Congo craton). Continental extrusion and lateral escape tectonics ensued, generating thousands-of-km long networks of anastomosing directional shear zones (keirogens), as a consequence of both the accretionary systems developed between the involved blocks and the highly deformable nature of the decratonized ribbon continents., (© 2023. The Author(s).)

Objective: To assess the diagnostic agreement between smartphone-enabled otoscopy and rigid otoendoscopy in tympanic membrane and middle ear diseases., Methods: A cross-sectional study was carried out to analyze otoscopies in patients seen at a general otorhinolaryngology (ORL) outpatient clinic, from June to December 2019. Eighty-three images of patients obtained from otoscopies performed through a smartphone device and a rigid endoscope were included, recorded, and stored for further analysis. The images were first analyzed by an experienced otologist, who assigned his diagnostic impression (defined as the gold standard) on each of the images. After this analysis, the images were displayed to a group of secondary raters (an experienced otorhinolaryngologist, a second-year resident in ORL, and a general practitioner). A questionnaire was applied related to each image., Results: There was high agreement between the smartphone device and the otoendoscopy images for all professionals, with a Kappa coefficient of 0.97 (p < 0.001). The smartphone device showed a diagnostic sensitivity of 81.1% and a specificity of 71.1%. As for the otoendoscopy, it showed a sensitivity of 84.7% and a specificity of 72.4%. The image classification as "2 = Good" was the most frequent one, with 34.9% for otoendoscopy and 31.6% for the smartphone device., Conclusion: There was a high diagnostic agreement between smartphone device-guided otoscopy and the rigid otoendoscopy, demonstrating the feasibility of using this device in clinical practice., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Adherence to secondary prevention measures after acute coronary syndrome (ACS) is essential to prevent disease recurrence. In Brazil, the Brazilian Unified Health System (SUS, in Portuguese), and the private healthcare system (PHCS) coexist. We aimed to evaluate the adherence to secondary prevention in patients with ACS who were assisted by either SUS or PHCS. In this longitudinal prospective study, patients with ACS were admitted to the four cardiological reference hospitals of Sergipe, three of which assisted PHCS users, and one, SUS users. We analyzed the two patient care models with multiple logistic regression models for adherence to physical activity, pharmacotherapy, and smoking cessation. We enrolled 581 volunteers in this study: 44.1 % from SUS and 55.9 % from PHCS. PHCS users showed greater adherence to pharmacotherapy at both 30 and 180 (p = 0.001) days after ACS with better results in all classes of medications (p < 0.05) than SUS users did. They also showed better adherence to physical activity (p = 0.047). There was no distinction between the groups regarding smoking cessation. The secondary prevention measures after ACS were more effective in PHCS users than in SUS users due to better adherence, especially to pharmacotherapy and regular physical activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Erectile dysfunction (ED) is the inability to achieve and/or maintain a penile erection sufficient for sexual satisfaction. Currently, many patients do not respond to the pharmacotherapy. The effects of a supplementation with Spirulina platensis , were evaluated in a model of ED induced by hypercaloric diet consumption. Wistar rats were divided into groups fed with standard diet (SD) or hypercaloric diet (HD) and supplemented with this alga at doses of 25, 50 or 100 mg/kg. Experimental adiposity parameters and erectile function were analyzed. In SD groups, Spirulina platensis reduced food intake, final body mass and adiposity index, and increased the total antioxidant capacity (TAC) of adipose tissue. However, no change was observed in erectile function. In the HD group, without Spirulina supplementation, a decrease in food intake was observed, in addition to an increase of final body mass, weight gain, adipose reserves, and adiposity index. Additionally, reduction in the number and increase in the latency of penile erection and adipose malondialdehyde levels, as well as a reduction in TCA was noted. Furthermore, cavernous contractility was increased, and the relaxing response was decreased. Interestingly, these deleterious effects were prevented by the algae at doses of 25, 50 and/or 100 mg/kg. Therefore, the supplementation with S. platensis prevents damages associated to a hypercaloric diet consumption and emerges as an adjuvant the prevention of ED.

(1) Background: Quality of life (QOL) is used as a health indicator to assess the effectiveness and impact of therapies in certain groups of patients. This study aimed to analyze the QOL of patients with acute coronary syndrome (ACS) who received medical treatment by a public or private health care system. (2) Methods: This observational, prospective, longitudinal study was carried out in four referral hospitals providing cardiology services in Sergipe, Brazil. QoL was evaluated using the Medical Outcomes Study 36-Item Short-Form Health Survey. The volunteers were divided into two groups (public or private health care group) according to the type of health care provided. Multiple linear regression models were used to evaluate QoL at 180 days after ACS. (3) Results: A total of 581 patients were eligible, including 44.1% and 55.9% for public and private health care, respectively. At 180 days after ACS, the public health care group had lower QoL scores for all domains (functional capacity, physical aspects, pain, general health status, vitality, social condition, emotional profile, and health) (p < 0.05) than the private group. The highest QoL level was associated with male sex (p < 0.05) and adherence to physical activity (p ≤ 0.003) for all assessed domains. (4) Conclusions: This shows that social factors and health status disparities influence QoL after ACS in Sergipe.

Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile erection. This disorder is related to psychosocial factors such as anxiety, depression, and low self-esteem, to organic factors such as the presence of preexisting conditions like hypertension, diabetes and dyslipidemia. The pathophysiology of the disease is related to changes in the neurotransmission of the autonomic or the non-cholinergic non-adrenergic nervous system, as well as the release of local mediators, such as thromboxane A 2 and endothelin, and hormonal action. These changes lead to impaired relaxation of cavernous smooth muscle, which reduces local blood flow and impairs penile erection. Currently, therapy is based on oral vasodilation, such as sildenafil, tadalafil, vardenafil and iodenafil, or by direct administration of these agents into the corpus cavernosum or by intraurethral route, such as alprostadil and papaverine. Despite this, studies that consolidate the understanding of its pathophysiological process contribute to the discovery of new more efficient drugs for the treatment of erectile dysfunction. In this sense, in the present work an extensive survey was carried out of the mechanisms already consolidated and the most recent ones related to the development of erectile dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Souza, Ferreira, Vasconcelos, Cavalcante and Silva.)

This study aimed to report the effects of different doses of ionizing radiation on inflammatory and repair stage of human skin graft adherence in Nude mice wounds. Animals were divided into transplanted with irradiated human skin grafts (IHSG) at 25 and 50 kGy (IHSG 25 kGy; IHSG 50 kGy) and non-IHSG and euthanized on the 3rd, 7th and 21st days after the surgery, by gross and microscopic changes, immunostaining for human type I collagen (Col I) and mouse Col I and Col III and inflammatory cells. We found an effectiveness of human split-thickness graft adherence in mice transplanted with IHSG 25 kGy, as well decrease in dermo-epidermal necrosis and neutrophils, lower loss of skin thickness, epithelization and neo-vascularization. Day 21 post-transplantation with IHSG 25 kGy was observed a well-preserved human skin in the border of the graft, a prominent granulation tissue in an organization by proliferated fibroblasts, Col III deposition and increased B-cells and macrophages. A complete adherence of human skin graft occurred with IHSG 25 kGy. We suggest that the ionizing radiation at 25 kGy mediates inflammation and the repair stage of human skin graft adherence in murine model, thus emerging as a potential tool in healing cutaneous wounds., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy., Methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment., Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023)., Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Several studies have examined the complement system in schizophrenia, suggesting an involvement of the lectin pathway. We analyzed 49 patients with schizophrenia and explored the association between psychopathology of schizophrenia and complement component 3 (C3) serum levels, C-reactive protein (CRP) serum levels, ficolin activation, and mannose-binding lectin (MBL) activation. In the multiple regression analysis, a negative association was observed between the Positive and Negative Syndrome Scale (PANSS) total score and ficolin activation. Body mass index (BMI) was positively associated with the serum levels of C3 and CRP. MBL activation was not associated with any independent variables. Our findings facilitate a better understanding of the complement system in schizophrenia. Additional studies with a large sample population are needed to confirm our results., (Copyright © 2021. Published by Elsevier B.V.)

Carotenoids are natural lipophilic pigments mainly found in plants, but also found in some animals and can be synthesized by fungi, some bacteria, algae, and aphids. These pigments are used in food industries as natural replacements for artificial colors. Carotenoids are also known for their benefits to human health as antioxidants and some compounds have provitamin A activity. The production of carotenoids by biotechnological approaches might exceed yields obtained by extraction from plants or chemical synthesis. Many microorganisms are carotenoid producers; however, not all are industrially feasible. Therefore, in this review, we provide an overview regarding fungi that are potentially interesting to industry because of their capacity to produce carotenoids in response to stresses on the cultivation medium, focusing on low-cost substrates.

Purpose: Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients., Methods: A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits., Results: Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group)., Conclusions: Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

This work explored the use of ozonation and photoperoxidation before the microfiltration process to reduce fouling. Produced water was synthesized with salt, viscosifier, and surfactant. The additives influence on membrane fouling was evaluated. Photoperoxidation process led to an overall better performance than ozonation in terms of oil removal and fouling reduction. The maximum oil removal efficiency was 86%, obtained for emulsions with salt after 2 h of treatment (COD: H 2 O 2 ratio 1:1, UV dose of 965 J/m 2 ). The inclusion of chemical additives impaired the oxidative power of hydroxyl radicals leading to a moderate oil removal; however, they were still able to reduce membrane fouling, mainly in oil/water emulsions with viscosifier. Higher salt concentration promoted fouling resistance and also benefited the permeate quality. Cross-flow microfiltration process integrated with photoperoxidation was able to improve the permeate flux from 84 to 182 L/m 2 .h after 3 h of exposure to UV radiation, resulting in a permeate with less than 10 mg/L of oil content. Graphical abstract.

The essential oil of Lippia microphylla (LM-OE) presents several pharmacological activities. This work evaluates the tocolytic effect of LM-OE on rats. LM-OE inhibited phasic contractions and relaxed tonic contractions on rat uterus. Considering that nitric oxide (NO) pathway regulates uterine contraction, LM-OE potency was attenuated in the presence of NO synthase (NOS) inhibitor and this reduction was reversed in the presence of a NOS substrate. Similarly, the relaxant potency of LM-OE was reduced in the presence of soluble guanylyl cyclase (sGC) and protein kinase G (PKG) inhibitors. LM-OE also demonstrates a positive modulation of large and small conductance calcium-activated, voltage-gated and adenosine triphosphate-sensitive potassium channels and inhibited curves to CaCl 2 as well as relaxed the uterus pre-contracted by S-(-)-Bay K8644, suggesting voltage-gated calcium channels type-1 (Ca V 1) blockade. Thus, the tocolytic effect of LM-OE on rat involves positive modulation of NO/NOS/sGC/PKG/K + -channels pathway and Ca 2+ influx blockade through Ca V 1.[Formula: see text].

Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna . (OC-EtOH) on acute toxicity and gastrointestinal motility ( in vitro and in vivo ) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl 2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H 1 and Ca V , and relaxation through Ca V blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea., (Copyright © 2020 Pereira, Figueiredo, de Oliveira, Ferreira, Aires Moreno, da Silva, Pinheiro, Santos, da Silva and Cavalcante.)

The objective of this study was to investigate the influence of long-term temperature stress during the in vitro maturation (IVM) of oocytes on the in vitro embryo production (IVP) and the abundance of HSP70 and HSP90 in zebu cattle. Viable cumulus-oocyte complexes (COCs) were incubated for 24 h at 37 °C, 38.5 °C, or 40 °C for the low-, physiological, and high-temperature stress treatments, respectively. Thereafter, they were subjected to in vitro fertilization and culture. Temperature did not affect the polar body extrusion. However, IVP was adversely affected when IVM took place at 37 °C and 40 °C. The highest abundance of HSP70 was observed in cumulus cells after maturation of COCs at 40 °C. In contrast, HSP70 was more abundant in oocytes at both 37 °C and 40 °C; however, at 40 °C, the difference to the control group (38.5 °C) was not significant. In contrast, the highest abundance of HSP90 was observed in oocytes and cumulus cells at 37 °C. It appears that HSP70 and HSP90 respond to cold and heat stress in different ways. In conclusion, moderately high (40 °C) and low (37 °C) thermal stress for 24 h during IVM is detrimental to the developmental competence of oocyte and is accompanied by changes in the abundances of HSP70 and HSP90, especially in cumulus cells., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Leptohyptis macrostachys , previously known as Hyptis macrostachys Benth., is used in folk medicine to relieve the symptoms of asthma, cough, and bronchitis. Recently, we showed that the ethanol extract obtained from Leptohyptis macrostachys has selective spasmolytic activity on guinea pig ileum. Therefore, the aim of this study was to characterize the spasmolytic mechanism of this extract, investigated whether it presents toxicological and antidiarrheal activities. Therefore, the crude ethanolic extract of Leptohyptis macrostachys was analyzed by high-performance liquid chromatographic-diode array detection (HPLC-DAD). The spasmolytic effect was evaluated on guinea pig ileum, toxicological activity using rats and antidiarrheal activity using male and female mice. In HPLC-DAD analysis, Rosmarinic acid (5.44%) was the most abundant phenolic compound, being considered as a chemical marker. The spasmolytic potency of the extract on histamine-induced contraction was reduced in the presence of 1 mM TEA + , a selective big-conductance K + channels blocker (BK Ca ). The extract produces a dose-dependent antidiarrheal activity, inhibiting equipotently defecation frequency and liquid stool formation. In addition, the extract has inhibited in a dose-dependent manner both castor oil-induced intestinal transit and intestinal fluid content. Thus, the spasmolytic activity of the extract involves positive modulation of BK Ca and its antidiarrheal activity is related to inhibition of intestinal motility and secretion., (Copyright © 2020 de Souza, de Vasconcelos, da Silva, Silva, Veloso, de Araújo, Costa, Pessôa, Tavares, da Silva, da Silva and Cavalcante.)

The article analyzes actions in the prevention and control of overweight and obesity that have been developed in the 92 municipalities (counties) in the state of Rio de Janeiro, Brazil, based on underlying principles in the typology of public policies developed by Lowi and Line of Care for Overweight and Obesity, according to the following analytical dimensions: program actions in prevention and control of obesity, characterization of macro policies according to the Lowi typology, and characterization of macro policies according to the Line of Care for Overweight and Obesity. The study is part of a research project from 2014 to 2018 that aimed to identify the strategies and challenges in the consolidation of the actions planned in the Line of Care for Overweight and Obesity, based on analysis of secondary data and government documents; searches in the municipalities' official websites; interviews; focus groups; and online questionnaires with health professionals and managers. The documents point to a series of actions such as individual consultations, support groups, health gyms, school health programs, and others, reinforced by the interviewees' narratives. Even with so many initiatives, the municipalities in the state of Rio de Janeiro face challenges with limited human resources and precarious infrastructure and equipment in the health units. To achieve mobilization in the actions to deal with obesity, the issue should be addressed specifically on the state and local agendas and not diluted among other activities and programs.

Introduction  The anatomy of the temporal bone is complex due to the large number of structures and functions grouped in this small bone space, which do not exist in any other region in the human body. With the difficulty of obtaining anatomical parts and the increasing number of ear, nose and throat (ENT) doctors, there was a need to create alternatives as real as possible for training otologic surgeons. Objective  Developing a technique to produce temporal bone models that allow them to maintain the external and internal anatomical features faithful to the natural bone. Methods  For this study, we used a computed tomography (CT) scan of the temporal bones of a 30-year-old male patient, with no structural morphological changes or any other pathology detected in the examination, which was later sent to a 3D printer in order to produce a temporal bone biomodel. Results  After dissection, the lead author evaluated the plasticity of the part and its similarity in drilling a natural bone as grade "4" on a scale of 0 to 5, in which 5 is the closest to the natural bone and 0 the farthest from the natural bone. All structures proposed in the method were found with the proposed color. Conclusion  It is concluded that it is feasible to use biomodels in surgical training of specialist doctors. After dissection of the bone biomodel, it was possible to find the anatomical structures proposed, and to reproduce the surgical approaches most used in surgical practice and training implants.

Background: During weight gain, most of the excess adipose tissue accumulates in the trunk. This alters the body shape and makes collection of anthropometric measurements, especially waist circumference (WC), difficult., Objective: To evaluate the sensitivity and applicability of additional abdominal measurements in order to assess body composition of obese women., Methods: A total of 30 women between 20 and 50 years of age and BMI above 30 kg/m² were assessed. Three WC measurements, were performed: at the umbilical scar designated as WC1 and at 8 and 16 cm above the umbilical scar, designated as WC2, and WC3 respectively. The correlation (r) between these anthropometric measurements and their sum was assessed against the parameters fat mass (FM), free fat mass (FFM), body fat percentage (%BF), and trunk fat percentage (%TF), obtained by total and trunk segmental bioelectric impedance analysis (BIA) as well as by the golden standard total and trunk dual energy X-ray absorptiometry (DXA)., Results: The measurements WC1, WC2, WC3, and their sum correlated strongly and moderately with the parameters FM, FFM, and %BF in total BIA and in both total DXA and trunk DXA., Conclusion: The results demonstrated a robust correlation between the sum of the three WC measurements and total and trunk DXA in obese women suggesting that such measurements may be a good indicator of body and trunk fat in women, actually superior to BIA results. The use of these three measurements may be an alternative for the assessment of body and trunk fat, in those cases in which the body shape due to adipose tissue trunk accumulation makes accurate classical measurement (WC1) difficult.

Asthma is a heterogeneous disease of the airways characterized by chronic inflammation associated with bronchial and smooth muscle hyperresponsiveness. Currently, different murine models for the study of asthma show poor bronchial hyperresponsiveness due to a scarcity of smooth muscle and large airways, resulting in a failure to reproduce smooth muscle hyperreactivity. Thus, we aimed to standardize a guinea pig model of chronic allergic lung inflammation mimicking airway smooth muscle hyperreactivity observed in asthmatics (Asth). Animals were randomly divided into a control group (Ctrl), which received saline (0.9% NaCl), and the Asth group, subjected to in vivo sensitization with ovalbumin (OVA) nebulization. Morphological analysis was performed by hematoxylin-eosin staining. Bronchial hyperresponsiveness was evaluated by nebulization time in the fifth, sixth, and seventh inhalations (NT5-7) and tracheal isometric contractions were assessed by force transducer. Total antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and protein expression by Western blot. Histologically, the Asth group developed peribronchial cellular infiltrate, epithelial hyperplasia and smooth muscle thickening. After the fourth nebulization, the Asth group developed bronchial hyperreactivity. The trachea from the Asth group contracted after in vitro stimulation with OVA, differing from the Ctrl group, which showed no response. Additionally, airway smooth muscle hyperreactivity to carbachol and histamine was observed in the Asth group only in intact epithelium preparations, but not to KCl, and this effect was associated with an augmented production of reactive oxygen species. Moreover, lung inflammation impaired the relaxant potency of isoproterenol only in intact epithelium preparations, without interfering with nifedipine, and it was found to be produced by transforming growth factor-β negative modulation of β adrenergic receptors and, furthermore, big-conductance Ca 2+ -sensitive K + channels. These effects were also associated with increased levels of phosphatidylinositol 3-kinases but not extracellular signal-regulated kinases 1/2 or phosphorylation, and augmented α-actin content as well, explaining the increased smooth muscle mass. Furthermore, pulmonary antioxidant capacity was impaired in the Asth group. Therefore, we developed a standardized and easy-to-use, reproducible guinea pig model of lung inflammation that mimics airway smooth muscle hypercontractility, facilitating the investigation of the mechanisms of bronchial hyperresponsiveness in asthma and new therapeutic alternatives.

Purpose: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined., Methods: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes., Results: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression., Conclusions: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

Antral follicular population (AFP) and anti-Müllerian hormone (AMH) concentration are strongly associated. Thus, analyzing AMH concentration is a reliable method to predict animals with high AFP, an important feature to select donor cows for embryos and oocytes. However, not much is known about this parameter in heifers, particularly in crossbred animals. The aim of this study was to assess AFP in heifers and cows and its relation to serum AMH levels. Bos taurus indicus cows (36-60-months-old; n = 30) and heifers (12-14-months-old; n = 17) of the same breed were evaluated. A single procedure of follicular counting was performed by ultrasound for each animal. Random sampling was performed to analyze serum AMH concentration. Cows showed higher AFP than heifers; nonetheless, plasma AMH concentration did not differ between the categories. A high correlation of AFP with plasma AMH concentration was observed in Girolando heifers. Thus, it is suggested that AMH concentration could be a reliable and less invasive method for selecting heifers with high AFP.

Ocular inflammatory diseases can present as isolated conditions but also as part of systemic inflammatory diseases. Anterior uveitis is closely related to SpA and shares the common genetic background of HLA-B27. Other ocular manifestations, such as episcleritis and scleritis, may also occur, although less frequently. Therefore, ocular involvement has been included as one of the important clinical features of SpA in the recently published classification criteria for axial and peripheral disease. However, there are a wide variety of aetiologies for ocular diseases and this must be considered in assessment of SpA., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Obesity is characterized by an excessive increase in body mass, leading to endothelial damage that may favor the development of erectile dysfunction (ED). ED is defined as the inability to achieve or maintain a penile erection long enough to have a sexual intercourse. In this context, different ED models were developed, however the high price of special animals or the long period to establish the disease has limited studies in this field. Therefore, this study proposed to establish and characterize a novel model of ED in rats associated to a hypercaloric diet consumption. Animals were randomly divided into control group (CG), which received a standard diet, and obese group (OG), fed with a hypercaloric diet during 8 weeks. Rat's erectile function was evaluated in vivo and in vitro . Food and caloric intake of OG were reduced compared to CG, due to an increased diet energy efficiency. However, OG presented an increased body mass, inguinal, retroperitoneal and epididymal adipose tissues, as well as body adiposity index at the end of experimental protocol. In erectile function analysis, there was a decrease in the number and the latency of penile erections in OG. Additionally, the contractile reactivity of corpus cavernosum was increased in OG, favoring penile detumescence and related to a reduced nitric oxide bioavailability and an increased in contractile prostaglandins levels as a consequence of endothelial damage. Moreover, the endothelium-relaxation reactivity of corpus cavernosum was attenuated in OG associated to the oxidative stress. Thus, it was provided a model for advances in sexual dysfunction field and drug discovery for ED treatment.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect different ocular structures, such as cornea, conjunctiva, episclera, sclera, uveal tract, retina, optic nerve and vessels. Neuro-ophthalmologic manifestations in SLE include different degrees of involvement of retina, choroid and optic nerve. Retinal changes are one of the most common ocular involvements and are frequently used as clinical criteria for activity, even if isolated. Studies show that up to 29% of patients with active SLE manifest retinal disease. The exact prevalence of choroidal disease is unknown, but is thought to be less common than retinopathy, due to under-diagnosis. Optic nerve disease, represented by optic neuritis and anterior/posterior ischaemic optic neuropathy, affects approximately 1% of SLE patients. These ocular manifestations have been associated with neurologic flares, antiphospholipid antibodies, nephropathy, and increased mortality. The aim of this paper is to review the different aspects of neuro-ophthalmologic involvement in SLE. Since these manifestations are frequent and potentially severe, a multi-professional team approach is needed to investigate properly and provide early aggressive treatment in order to avoid visual sequelae.

Previously, we demonstrated that caulerpine has spasmolytic effect on guinea pig ileum. The aim of this study was to investigate pathways of its spasmolytic action. We test caulerpine against phasic contractions induced by carbachol in the circular layer of guinea pig ileum and this alkaloid did not inhibit these contractions, indicating that caulerpine did not interfering with the mobilisation of Ca 2+ from intracellular stores. Additionally, the spasmolytic effect of caulerpine did not involve K + channels. Furthermore, we observed that α 2 -adrenergic receptors were not involved in the spasmolytic effect of caulerpine, since the relaxation curve induced by caulerpine was not shifted in the presence of yohimbine (α 2 -adrenergic antagonist). However, in the presence of propranolol (β-adrenergic antagonist), the relaxation curve induced by caulerpine was right-shifted, resulting in a fivefold increase in EC 50 . Thus, a possible mechanism for the spasmolytic action of caulerpine is the activation of β-adrenergic receptors.

Background: The common hematophagous bat, Desmodus rotundus, is one of the main wild reservoirs of rabies virus in several regions in Latin America. New production practices and changed land use have provided environmental features that have been very favorable for D. rotundus bat populations, making this species the main transmitter of rabies in the cycle that involves humans and herbivores. In the Amazon region, these features include a mosaic of environmental, social, and economic components, which together creates areas with different levels of risk for human and bovine infections, as presented in this work in the eastern Brazilian Amazon., Methodology: We geo-referenced a total of 175 cases of rabies, of which 88% occurred in bovines and 12% in humans, respectively, and related these cases to a number of different geographical and biological variables. The spatial distribution was analyzed using the Kernel function, while the association with independent variables was assessed using a multi-criterion Analytical Hierarchy Process (AHP) technique., Findings: The spatiotemporal analysis of the occurrence of rabies in bovines and humans found reduction in the number of cases in the eastern state of Pará, where no more cases were recorded in humans, whereas high infection rates were recorded in bovines in the northeastern part of the state, and low rates in the southeast. The areas of highest risk for bovine rabies are found in the proximity of rivers and highways. In the case of human rabies, the highest concentration of high-risk areas was found where the highway network coincides with high densities of rural and indigenous populations., Conclusion: The high-risk areas for human and bovine rabies are patchily distributed, and related to extensive deforested areas, large herds of cattle, and the presence of highways. These findings provide an important database for the generation of epidemiological models that could support the development of effective prevention measures and controls.

The eye is divided anatomically in three layers: an outer or fibrous layer (cornea/sclera), middle or vascular layer (uvea - iris, ciliary body, and choroid) and an inner or sensorineural layer (retina). They compose the several anatomic and functional layers that enable the immune protection of the eye. The first layer involves an intact anatomic border with the blood-ocular barrier and immunosuppressive neuropeptides in the native aqueous humor. The second layer trusts on the capability of the eye to reestablish an immunosuppressive micro-environment by activating latent TGF-β and reestablishing the anterior chamber-associated immune deviation. The third layer involves a mechanism that is not yet completely recognized, but that has the ability to overcome a predominantly Th1 intraocular immune response and to reestablish anterior chamber-associated immune deviation. Understanding the comprehensive mechanisms of these pathways, will lead to the development of new treatments strategies in order to prevent damage to the eye from persistent or exacerbated inflammation, directed at first to pathogens, but that may develop an autoimmune reaction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Alopecia areata is understood as an autoimmune disease T cell-mediated mainly involving hair follicles in humans. It is a multifactorial aetiologic disease characterised by non-scarring alopecia and asymptomatic areas, affecting approximately 2 % of dermatology patients. Recent studies suggest that the pathogenesis of AA plays an important role in the association of certain HLA groups, neuroendocrine parameters and immunogenic factors. During 3 months (March to May 2013) at Hospital Clínic de Barcelona, 22 patients with severe alopecia areata underwent ophthalmic examination to determine whether there were ocular findings in the following parameters: Best-corrected visual acuity on decimal Snellen optotype, anterior segment slit-lamp examination and photograph, intraocular pressure measurement and dilated fundoscopy. Ultra-wide-field retinal imaging with or without red-free photograph was carried out with the Optomap 200 Tx (Optos, DunFermline, UK). Forty-four eyes of 22 patients were analysed [15 females (68.2 %)]. The mean age was 38.9 (SD 13.7) and mean time of evolution was 19.9 years (SD 16.3). Alopecia areata clinical patterns were multifocal [n = 10 (45.5 %)], universalis [n = 7 (31.8 %)], totalis [n = 3 (13.6 %)] and focal [n = 2 (9.1 %)]. Best-corrected visual acuity was 1.0 in almost all patients, but only three eyes (6.8 %) had vision of 0.7. Ocular findings were as follows: madarosis [n = 7 partial loss of eyelashes (31.85 %) and n = 4 total loss (18.2 %)], lens changes [n = 4 (18.2 %)], cataract [n = 3 (13.65 %)]. Ultra-wide fundus photography examination showed peripheral drusen [n = 17 eyes (38.6 %)], white-without-pressure changes [n = 8 eyes (18.22 %)] and peripheral retinal degenerations [n = 3 eyes (6.81 %)]. Ocular findings in patients with alopecia areata are reported and discussed by dermatologic and ophthalmic evaluation.

Ruthenium-derived complexes have emerged as new nitric oxide (NO) donors that may help circumvent the NO deficiency that impairs vasodilation. NO in vessels can be produced by the endothelial cells and/or released by NO donors. NO interacts with soluble guanylyl-cyclase to produce cGMP to activate the kinase-G pathway. As a result, conductance arteries, veins and resistance arteries dilate, whereas the cytosolic Ca(2+) levels in the smooth muscle cells decrease. NO also reacts with oxygen or the superoxide anion, to generate reactive oxygen species that modulate NO-induced vasodilation. In this article, we focus on NO production by NO synthase and discuss the vascular changes taking place during hypertension originating from endothelial dysfunction. We will describe how the NO released from ruthenium-derived complexes enhances the vascular effects arising from failed NO generation or lack of NO bioavailability. In addition, how ruthenium-derived NO donors induce the hypotensive effect by vasodilation is also discussed.

Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant -116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, -116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the -116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of -116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides.

Artibeus obscurus (Mammalia: Chiroptera) is endemic to South America, being found in at least 18 Brazilian states. Recent studies revealed that different populations of this genus present distinct phylogeographic patterns; however, very little is known on the population genetics structure of A. obscurus in the Amazon rainforest. Here, using a fragment (1010bp) of the mitochondrial gene cytochrome b from 87 samples, we investigated patterns of genetic divergence among populations of A. obscurus from different locations in the Brazilian Amazon rainforest and compared them with other Brazilian and South American regions. Analysis of molecular variance (AMOVA), fixation index (Fst) analysis, and phylogeographic patterns showed divergence between two major monophyletic groups, each one corresponding to a geographic region associated with the Atlantic and Amazon forest biomes. The Atlantic forest clusters formed a monophyletic group with a high bootstrap support and a fragmented distribution that follows the pattern predicted by the Refuge Theory. On the other hand, a different scenario was observed for the Amazon forest, where no fragmentation was identified. The AMOVA results revealed a significant geographic heterogeneity in the distribution of genetic variation, with 70% found within populations across the studied populations (Fst values ranging from 0.05864 to 0.09673; φST = 0.55). The intrapopulational analysis revealed that one population (Bragança) showed significant evidence of population expansion, with the formation of 2 distinct phylogroups, suggesting the occurrence of a subspecies or at least a different population in this region. These results also suggest considerable heterogeneity for A. obscurus in the Amazon region.

Autoimmune uveitis (AIU) is among the leading causes of preventable blindness. It can be isolated, precede, or appear in the course of a systemic autoimmune inflammatory disease. When suspected, AIU should be promptly referred to an ophthalmologist for proper anatomic classification and local treatment. In recurrent and chronic forms, systemic treatment should be started, usually with corticosteroids and immunesuppressors. In cases of lack of efficacy or intolerance, biologic agents such as monoclonal antibodies anti-TNF (infliximab and adalimumab) and others (abatacept and tocilizumab) are being used. The clinical diseases associated to AIU and the experimental models have helped in the understanding of the pathogenic mechanism. The treatment schemes have improved, and recent advances in basic knowledge are leading to even more effective targeted therapies.