An Overview of Management Control Theory

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Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease

OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype

Inferior petrosal sinus catheterization: technical aspects

OBJETIVO: O cateterismo dos seios petrosos inferiores (SPI) ajuda a diferenciar as formas hipofisária e ectópica na síndrome de Cushing (SC). O objetivo desse trabalho é descrever a técnica empregada em nosso serviço, discutir a solução de dificuldades e verificar o índice de sucesso atingido. CASUÍSTICA E MÉTODO: Foram submetidos a cateterismo bilateral dos SPI 42 pacientes com SC, entre setembro de 2000 e setembro de 2005. As dificuldades para o posicionamento do cateter foram correlacionadas com as soluções empregadas. RESULTADOS: As variações anatômicas, a semelhança entre o SPI e a veia emissária do plexo basilar e a dificuldade de contrastar as estruturas a contrafluxo para localizá-las foram os principais problemas. Foram utilizados cateter pré-moldado, fio-guia semicurvo e dirigível, road-maping e venografia por injeção contralateral, além de critérios para diferenciar o SPI da veia emissária. Dos 84 SPI abordados, um apresentava trombose, e dos 83 possíveis, 80 (96,4%) foram cateterizados. Não se observaram complicações. CONCLUSÃO: A cateterização dos SPI pode ser feita na maioria dos pacientes. A identificação da veia emissária do plexo basilar e o uso de flebografia por injeção contralateral melhoraram o desempenho do método.PURPOSE: Inferior petrosal sinus catheterization and sampling for corticotropin dosage helps to differentiate hypophisary and ectopic forms of Cushing syndrome. The aim of this paper is to describe the technique used in inferior petrosal sinus catheterization in our service, emphasizing the solution found for frequent difficulties, and verify the success rate achieved. PATIENTS AND METHODS: Between September/2000 and September/2005, forty-two (eighty-four sinuses) patients were submitted to inferior petrosal sinus sampling. The difficulties for correct catheter positioning were identified and correlated with their solutions. RESULTS: Anatomical variations, similarity between IPS and emissary vein of the basilar plexus and unfavorable flow to the contrastation of the structures (retrograde catheterization) were the main problems. Using pre-shaped catheters, curved, steerable guide-wires, road-maping and venography by contalateral injection, besides criteria to differentiate IPS from the emissary vein. Of the 84 sinuses approached, one was thrombosed, and 80 (96.4%) of 83 possible were selectively catheterized. No clinical complication occurred. CONCLUSION: IPSC can be safe and successfully performed in most cases. The identification of the emissary vein of the basilar plexus and use of venography by contralateral injection, improved the method performance

Extraction of bioactive compounds from plants as promising agentes against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogenic virus with high transmissibility and infectivity, which began to spread across the globe in late 2019, which soon became the COVID-19 pandemic, causing social and economic impacts. In response to this situation, the scientific community started the development of effective substances against this virus. Bioactive molecules present in plants, mainly phenolic compounds, are promising altematives to combat pathological disorders. Therefore, the objective of this work was to use the aqueous extract of a mountain plant as an antiviral substance to neutralize COVID-19. MaterialslMethods: The mountain plant extract was obtained by dynamic maceration in water for I hour (twice). Afier obtaining the extracts, they were evaluated for their phenolic profile by high performance líquid chromatography coupIed to a diode array detector and a mass spectrometer detector (HPLC-DAD-MS). Cytotoxicíty was determined by the sulphorhodamine B assay in Vero cells, as well as the evaluation ofthe antivíral activity. Results: Regarding the phenolic profile, the main compounds found were trigalloyl-HHDPglucoside; pentagalloyl glucose, quercetin 3-0-glucuronide and quercetin O-hexoside. The GI50 (concentration able to inhibit 50% of cell proliferation) and the MNCC (maximum concentration without toxicity) were between 100 and 180.3 J.lg/rnL and between 85 and 120 J.lg/rnL, respectively. The MNCC value was obtained considering the concentration that allowed 90% of celI proliferation of Vero cells. In relation to the viral activity screening, the results achieved for the viral titre were between 5000 and 9000 PFU/rnL, while for the antiviral activity ranged between 0.5 and 3.0 Mv, being the percentage ofreduction in a range of85-95 %. • Conclusion: The mountain plant extracts showed in its composition bioactive compounds and consistent results of antiviral activity. Moreover, it presents itself as a potential substance for protection applications against the COVID-19 virus. However, further studies in specific products are required for validation and implementation.The authors are grateful to the Foundation for Science and Technology (FeT, Portugal) for financiai support tbrough national funds FCT/MCTES to the CIMO (UIDB/00690/2020). M.C. Pedrosa tbanks "PlantCovid" projeci for her scholarship. S. Helena and M. Carocho fhank FCT for their individual emplayment program·contract (CEECTND/00831/20J8, CEECINDI03040/2017). L. Barros also thanks the national funding by FCr , through the institutional scientific employment program--contract for her contract. Acknowledgments to the Project financed by the European Fund for Regional Development (Fundo Europeu de Desenvolvimento Regional (FEDER)) through lhe Programa Operacional Regional Norte 2020, within the "PlantCovid" project, NORTE-01-02B7-FEDER-054870info:eu-repo/semantics/publishedVersio

Reinforcement Learning para treino do Pac-Man em Speedrun / Reinforcement Learning for Pac-Man Speedrun Training

Os algoritmos de Reinforcement Learning têm o objetivo de melhorar o comportamento do agente em um ambiente específico. Esses algoritmos se mostraram excelentes na melhoria da inteligência artificial em games de diversos gêneros. Nesse trabalho é usado o algoritmo Q-Learning do Reinforcement Learning aplicado no jogo Pac-Man, um dos jogos mais tradicionais que fomentam o desenvolvimento de novos algoritmos para a área de inteligência artificial. O objetivo principal é treinar o Pac-Man para escolher os melhores caminhos e assim terminar o jogo o mais rápido possível, de acordo com o modo de jogo speedrun. Os resultados obtidos por esse trabalho mostraram que foi possível fazer o Pac-Man ter bons resultados no modo speedrun

Multicompartment body composition analysis in older adults: a cross-sectional study

Background During aging, changes occur in the proportions of muscle, fat, and bone. Body composition (BC) alterations have a great impact on health, quality of life, and functional capacity. Several equations to predict BC using anthropometric measurements have been developed from a bi-compartmental (2-C) approach that determines only fat mass (FM) and fat-free mass (FFM). However, these models have several limitations, when considering constant density, progressive bone demineralization, and changes in the hydration of the FFM, as typical changes during senescence. Thus, the main purpose of this study was to propose and validate a new multi-compartmental anthropometric model to predict fat, bone, and musculature components in older adults of both sexes. Methods This cross-sectional study included 100 older adults of both sexes. To determine the dependent variables (fat mass [FM], bone mineral content [BMC], and appendicular lean soft tissue [ALST]) whole total and regional dual-energy X-ray absorptiometry (DXA) body scans were performed. Twenty-nine anthropometric measures and sex were appointed as independent variables. Models were developed through multivariate linear regression. Finally, the predicted residual error sum of squares (PRESS) statistic was used to measure the effectiveness of the predicted value for each dependent variable. Results An equation was developed to simultaneously predict FM, BMC, and ALST from only four variables: weight, half-arm span (HAS), triceps skinfold (TriSK), and sex. This model showed high coefficients of determination and low estimation errors (FM: R2adj: 0.83 and SEE: 3.16; BMC: R2adj: 0.61 and SEE: 0.30; ALST: R2adj: 0.85 and SEE: 1.65). Conclusion The equations provide a reliable, practical, and low-cost instrument to monitor changes in body components during the aging process. The internal cross-validation method PRESS presented sufficient reliability in the model as an inexpensive alternative for clinical field use.info:eu-repo/semantics/publishedVersio

A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

The treatment objectives for a patient with Cushing’s disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails.There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Objectives: This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods: A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results: The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions: The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID