Infertilidade masculina associada ao uso de finasterida

Finasteride is a potent and specific inhibitor of the 5alpha-reductase enzyme in men. Clinical studies have shown that finasteride 1mg/day is effective for promoting hair growth in men with male pattern hair loss. However, there is a concern about the use of finasteride, especially in young fertile patients, because of its action on testosterone metabolism. This paper describes 3 cases of young patients who had very poor seminal quality during finasteride treatment (1 mg/day), and their seminal quality greatly improved after cessation of finasteride treatment. Two of them presented with a left varicocele and the other was obese. We hypothesize that finasteride may not dramatically change the spermatogenesis process in healthy men, but in patients with conditions related to infertility, an amplification of the negative influence of finasteride could occur. Future studies should be done to clarify the extent of the effect of finasteride in patients fertility problems.A finasterida é um potente e específico inibidor da enzima 5alfa-redutase em homens. Estudos clínicos demonstraram que finasterida 1mg/dia diminui a progressão da queda e aumenta o crescimento do cabelo em homens que sofrem de queda de cabelo hereditária. Por sua influência no metabolismo dos andrógenos existe uma preocupação a respeito do seu uso, principalmente em pacientes em idade fértil. Neste trabalho são descritos 3 casos de pacientes jovens, que apresentaram piora do espermograma durante o uso continuado de finasterida 1mg revertida após a suspensão do mesmo. Dois deles tinham varicocele unilateral e o terceiro era obeso. Aparentemente o tratamento com finasterida promoveu alteração significativa na qualidade seminal. Pode-se especular que talvez a finasterida por si só não traga alteração para a espermatogênese como reportado por Overstreet et al. (1999), mas que em pacientes de risco com possíveis causas de infertilidade associadas, possa ocorrer a amplificação da influência deletéria da finasterida. Estudos futuros devem ser realizados para esclarecer a influência da finasterida nestes pacientes

OS FEEDBACKS SOB O OLHAR DO ALUNO NA UNIVERSIDADE: ESTRATÉGIAS PARA O DESENVOLVIMENTO DO LETRAMENTO ACADÊMICO

No processo de ensino e aprendizagem, várias estratégias de leitura e escrita são fundamentais para que o desenvolvimento acadêmico se torne significativo para os sujeitos envolvidos. Dentro dessas estratégias, acreditamos que os feedbacks disponibilizados pelos docentes são instrumentos fundamentais para que os educandos tenham um crescimento acadêmico efetivo. Nesse contexto, a presente pesquisa é de cunho qualitativo e se insere no campo da Linguística Aplicada, com o objetivo de investigar as representações que os alunos do oitavo período do curso de Letras/Português, de uma universidade pública no estado do Tocantins, têm acerca da importância dos feedbacks na constituição do letramento acadêmico. Destarte, o feedback escrito é um instrumento didático que o professor pode utilizar para acompanhar e orientar os seus alunos durante o processo de ensino e aprendizagem. A partir desta pesquisa, podemos confirmar e reforçar a importância deste instrumento no desenvolvimento do letramento acadêmico dos universitários. Tal instrumento, no discurso dos participantes, demonstrou ser uma ferramenta potencializadora do modelo de Letramento Acadêmico (LEA; STREET, 2014). Além disso, ficou evidenciado como o papel do professor é indispensável para o desenvolvimento crítico e responsivo do aluno na Universidade.PALAVRAS-CHAVE: Feedback. Letramento acadêmico. Aprendizagem significativa.DOI: https://doi.org/10.47295/mgren.v7i1.156

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs

Parameters influencing the size of chitosan-TPP nano- and microparticles

Chitosan nanoparticles, produced by ionic gelation, are among the most intensely studied nanosystems for drug delivery. However, a lack of inter-laboratory reproducibility and a poor physicochemical understanding of the process of particle formation have been slowing their potential market applications. To address these shortcomings, the current study presents a systematic analysis of the main polymer factors affecting the nanoparticle formation driven by an initial screening using systematic statistical Design of Experiments (DoE). In summary, we found that for a given chitosan to TPP molar ratio, the average hydrodynamic diameter of the particles formed is strongly dependent on the initial chitosan concentration. The degree of acetylation of the chitosan was found to be the second most important factor involved in the system's ability to form particles. Interestingly, viscosimetry studies indicated that the particle formation and the average hydrodynamic diameter of the particles formed were highly dependent on the presence or absence of salts in the medium. In conclusion, we found that by controlling two simple factors of the polymer solution, namely its initial concentration and its solvent environment, it is feasible to control in a reproducible manner the production and characteristics of chitosan particles ranging in size from nano- to micrometres

To be or not to be a pseudogene: a molecular epidemiological approach to the mclx genes and its impact in tuberculosis

Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal, and cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER), and from Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). H.N.-G. received a personal FCT Grant (SFRH/BD/33902/2209). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Conservation of geosites as a tool to protect geoheritage: the inventory of Ceará Central Domain, Borborema Province - NE/Brazil

The Ceará Central Domain, in the northern Borborema Province/NE Brazil, encompasses important geological records (geosites) which allow understanding a relevant period of the Earth’s evolution, mainly associated to Neoproterozoic Brazilian/Pan-African Cycle and West Gondwana amalgamation, besides Neoarchean to Ordovician records. The presented geoheritage inventory aims to characterise the geosites with scienti c relevance of Ceará Central Domain. By applying a method for large areas, the nal selection resulted in eight geological frameworks represented by 52 geosites documented in a single database. This is the rst step for a geoconservation strategy based on systematic inventories, statutory protection, geoethical behaviour and awareness about scienti c, educational and/or cultural relevance of geosites.We specially thank all experts that helped us with this inventory: Afonso Almeida, Carlos E.G. de Araújo, César Veríssimo, Christiano Magini, Clóvis Vaz Parente, Felipe G. Costa, Irani C. Mattos, Neivaldo de Castro, Otaciel de Melo, Sebástian G. Chiozza, Ticiano Santos and Stefano Zincone. We are also thankful to Kátia Mansur, Ricardo Fraga Pereira and anonymous reviewers for their valuable contributions. PM is grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for PhD mobility scholarship PDSE Program/Process n 88881.132168/2016-01info:eu-repo/semantics/publishedVersio

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration