Universal and Specific Functions of STAT3in Solid Tumours

STAT3 is constitutively activated in a high percentage of tumours and tumourderived cells of both liquid and solid origin, often correlating with aggressive disease and bad prognosis. Persistent STAT3 activity, to which tumours often become addicted, is mostly due to the aberrant activation of pro-oncogenic/proinflammatory signals that can trigger its phosphorylation, such as oncogenes, growth factor receptors and cytokines. Among STAT3-mediated functions are increased survival and proliferation, enhanced angiogenesis, motility and invasion, and down-modulation of anti-tumour immune responses. Moreover, STAT3 was recently shown to play unexpected roles in regulating cell metabolism and mitochondrial activity via both transcriptional and non-transcriptional mechanisms. Here, we review the main knowledge about the role of STAT3 in solid tumours, with a particular focus on breast cancer and our recent work with mouse models

Models for estimating leaf area in the ‘Palmer’ mango

Techniques for measuring leaf area are basic for evaluating plant growth in the mango. As such, the aim of this study was to determine the leaf area of the ‘Palmer’ mango using mathematical models proposed by the present study, and compare the results of the proposed models with models available in the literature for other mango cultivars. The mango leaf was simulated as a function of leaf length (L) and width (W) using two distinct geometric models: an ellipse and a rosacea petal. Models found in the literature and determined for other cultivars, were also tested. The values for leaf area were obtained using the ImageJ software and taken at their actual value; these were later compared with the values achieved by the geometric models. The models were tested for quality of prediction through cross-validation. The models proposed in the present study were not superior to the best models found in the literature. The model LA = 3.80 + 0.67 (LW) achieved the best performance, with a mean absolute percentage error (MAPE) of 3.78%. Using only length, the best model was LA = 0.0142C2 + 6.1902C - 49.444, with a MAPE of 4.07%. The use of mathematical models proved to be a suitable option for estimating leaf area in the ‘Palmer’ mango. Moreover, the use of R2 as the only form of model quality assessment can lead to errors in choosing the best model

Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favors spontaneous immortalization by opposing differentiation and senescence checkpoints

STAT3, a pleiotropic transcription factor acting downstream of cytokines and growth factors, is known to enhance proliferation, migration, invasion and aerobic glycolysis in tumors upon aberrant activation. In the murine epidermis, STAT3 is necessary for experimentally induced carcinogenesis. Skin tumorigenesis is conversely enhanced by overexpression in keratinocytes of the constitutively active STAT3C mutant, which also induces robust, psoriasis-like epidermal hyperplasia. We show here that STAT3C expression at physiological levels in knock-in mice leads to mild epidermal hyperplasia and attenuated expression of terminal differentiation markers. Altered differentiation is confirmed in isolated primary epidermal keratinocytes in vitro, correlating with enhanced proliferative and clonogenic potential, attenuated senescence and, strikingly, high-frequency spontaneous immortalization. These results suggest that moderate levels of continuous STAT3 activation, which closely resemble those triggered by chronic inflammation or persistent growth factor stimulation, may establish a preneoplastic state in part by promoting the escape of epidermal progenitor cells from differentiation and senescence checkpoints

ESTUDO DAS NORMAS DE SEGURANÇA EM EVENTOS NOS HOTÉIS AFILIADOS À ABIH DA COSTA VERDE E MAR

Neste trabalho buscamos estudar a aplicação das normas de segurança direcionadas aos espaços de eventos nos hotéis filiados à ABIH da Costa Verde e Mar. Como procedimento utilizamos da pesquisa exploratória e como instrumento de coleta de dados do questionário, direcionado aos profissionais atuantes no setor de eventos. Desta forma, identificamos os quesitos e normas de segurança aplicáveis a eventos, avaliamos o cumprimento das normas pelos meios de hospedagem, para então confrontar os resultados encontrados com a legislação específica. Como resultados, identificamos que quase todos os empreendimentos se mantêm de acordo com as normas de segurança, cumprindo a legislação estabelecida pelos órgãos competentes. No entanto, observamos que nem todos os empreendimentos atendem ao que recomendam os autores da área no que diz respeito à qualificação dos profissionais que atuam no setor de eventos

Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation

Extracellular microfibrils composed of fibrillin-1 and -2 regulate bone formation through modulation of TGF-β and BMP signaling

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life