IGF-I influences everolimus activity in medullary thyroid carcinoma

Context: Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and in two human MTC primary cultures. Objective: To verify whether IGF-I may influence the effects of everolimus in a group of human MTC primary cultures. Design: We collected 18 MTCs that were dispersed in primary cultures, treated without or with 10 nM-1 mu M everolimus and/or 50 nM IGF-I. Cell viability was evaluated after 48 h, and calcitonin (CT) secretion was assessed after a 6 h incubation. IGF-I receptor downstream signaling protein expression profile was also investigated. Results: Everolimus significantly reduced cell viability in eight MTC [by similar to 20%; P < 0.01 vs. control; everolimus-responders (E-R) MTCs], while cell viability did not change in 10 MTCs [everolimus-non-responders (E-NR) MTCs]. In E-R MTCs, IGF-I blocked the antiproliferative effects of everolimus that did not affect CT secretion, but blocked the stimulatory effects of IGF-I on this parameter. IGF-I receptor downstream signaling proteins were expressed at higher levels in E-NR MTC as compared to E-R MTCs. Conclusion: IGF-I protects a subset of MTC primary cultures from the antiproliferative effects of everolimus and stimulates CT secretion by an mTOR mediated pathway that, in turn, may represent a therapeutic target in the treatment of aggressive MTCs

Multimodal models of animal sex in scientific literature: breaking binaries leads to a better understanding of ecology and evolution

‘Sex’ is often used to describe a suite of phenotypic and genotypic traits of an organism related to reproduction. However, not all these traits are necessarily linked, and the rhetorical collapse of variation into a single term elides much of the complexity inherent in reproductive phenotypes. We conducted a meta-analysis of scientific literature to investigate how terminology related sexual phenotypes changes over time. We find that the conflation of gender and sex has increased, and there is a mammalian bias in this conflation. We highlight how a more inclusive and expansive framework for sex can clarify studies of sexual diversity

Early Detection of Mental Health of Doctoral Students UAD due to the Covid-19 Pandemic through the Questionnaire Method

Stress and a decrease in student learning achievement can be triggered by the mal-adaptive coping experienced, especially during the COVID-19 pandemic which requires students to adjust physically and psychologically in the learning process on campus which is now done online and is more independent in learning. So, psychological support for students, especially UAD doctoral students, needs to be done, one of which is mental health screening. The purpose of this study was to determine the mental health condition and social support of students. In the end, this will be the basis for providing psychological support and improving educational and learning activities for UAD Doctoral program students. The research method used was the adjustment and validation of the Self-Report Questionnaire (SRQ) 29, covering aspects of mental health, namely anxiety, depression, stress, use of psychostimulants/substances, symptoms of psychosis (reality rating disorder) and post-traumatic stress disorder (PTSD); Customize and validate social support questionnaires; Submission of ethical review; and Conducting an online survey of mental health, anxiety, depression and social support for Doctoral students. The results obtained from SRQ29 showed that as many as 30% of students experienced PTSD and 10% experienced depression. However, the results of the high religiosity test and quality of life were not compromised. The conclusion of this study is that the existence of religiosity and spirituality can provide positive coping to reduce mental disorders and improve the quality of life for students during the COVID-19 pandemic

life cycle assessment lca of landfill gas management comparison between conventional technologies and microbial oxidation systems

Abstract The reduction of landfill gas emissions is a central issue of the Directive 99/31/EC. Biofilters and biocovers have been identified as an alternative and cost-effective technologies to mitigate impacts due to CH4 and NMVOCs emissions. The Life Cycle Assessment demonstrates the environmental sustainability of biofiltration systems, with the aim of improving the environmental impact indicators such as Global Warming (-10.75% for Biofilter and -11.60% for Biocover) and Photochemical oxidation (-7.97% for Biofilter and -8.61%. for Biocover). This paper shows that these treatment technologies are effective for methane oxidation when the calorific value of the LFG is low, thus they maximize the amount of treated gas during the after-care phase

Characterization of Keratinocyte Differentiation Induced by Ascorbic Acid: Protein Kinase C Involvement and Vitamin C Homeostasis11The authors declared not to have a conflict of interest.

Epidermal keratinocytes undergo differentiation in response to several stimuli to form the cornified envelope, a structure that contributes to the barrier function of skin. Although differentiation has been extensively analyzed, the precise role of vitamin C during this process is still not defined. Ascorbic acid, besides acting as a radical scavenger, has been shown to promote mesenchymal differentiation. In this study, we found that keratinocytes grown in ascorbate-supplemented medium developed a differentiated phenotype, as demonstrated by enhanced expression of marker genes and increase in cornified envelope content. The pro-differentiating effects of ascorbate were mediated by the protein-kinase-C-dependent induction of activating protein 1 DNA binding activity; indeed, down-modulation of protein kinase C activity abolished differentiation triggered by ascorbic acid. Although vitamin C appeared to regulate the same signaling pathway modulated by calcium, a classical in vitro inducer of epidermal differentiation, nonetheless terminally differentiated keratinocytes exhibited different ascorbate homeostasis and cellular antioxidant status. Indeed, we found that, unlike calcium, differentiation promoted by ascorbate was accompanied by (i) an enhanced ascorbate transport, due to overexpression of specific transporters, (ii) a great efficiency of dehydroascorbate uptake, and (iii) an increase in glutathione content with respect to proliferating cells. Ascorbic acid may be useful to promote epidermal differentiation, avoiding depletion of hydrophilic antioxidant stores

COMUNICAÇÃO EM AMBIENTES MULTICULTURAIS: PRODUÇÃO ACADÊMICA BRASILEIRA - 2000 a 2016

O presente trabalho teve por objetivo analisar as contribuições acadêmicas sobre a comunicação em ambientes multiculturais de trabalho, durante o período de 2000 a 2016, no Brasil. Com abordagem qualitativa, a pesquisa foi do tipo descritiva com o uso do procedimento técnico de revisão bibliográfica. Foram analisados trinta e três trabalhos acadêmicos que foram organizados em três períodos de publicação. Como resultados, foram apresentados e discutidos alguns elementos relacionados à comunicação intercultural, como as competências e os traços de personalidade mais indicados para a gestão de equipes, os problemas identificados nas bases educacionais, o fluxo de expatriação nas empresas multinacionais, a necessidade de estudos sobre organizações de menor porte, os principais problemas e desafios no desenvolvimento de profissionais diante de diferentes culturas

Age of Insomnia Onset Correlates with a Reversal of Default Mode Network and Supplementary Motor Cortex Connectivity

Insomnia might occur as result of increased cognitive and physiological arousal caused by acute or long acting stressors and associated cognitive rumination. This might lead to alterations in brain connectivity patterns as those captured by functional connectivity fMRI analysis, leading to potential insight about primary insomnia (PI) pathophysiology as well as the impact of long-term exposure to sleep deprivation. We investigated changes of voxel-wise connectivity patterns in a sample of 17 drug-naïve PI patients and 17 age-gender matched healthy controls, as well as the relationship between brain connectivity and age of onset, illness duration, and severity. Results showed a significant increase in resting-state functional connectivity of the bilateral visual cortex in PI patients, associated with decreased connectivity between the visual cortex and bilateral temporal pole. Regression with clinical scores originally unveiled a pattern of increased local connectivity as measured by intrinsic connectivity contrast (ICC), specifically resembling the default mode network (DMN). Additionally, age of onset was found to be correlated with the connectivity of supplementary motor area (SMA), and the strength of DMN←→SMA connectivity was significantly correlated with both age of onset (R2 = 41%) and disease duration (R2 = 21%). Chronic sleep deprivation, but most importantly early insomnia onset, seems to have a significant disruptive effect over the physiological negative correlation between DMN and SMA, a well-known fMRI marker of attention performance in humans. This suggests the need for more in-depth investigations on the prevention and treatment of connectivity changes and associated cognitive and psychological deficits in PI patients

Urokinase Induces Basophil Chemotaxis through a Urokinase Receptor Epitope That Is an Endogenous Ligand for Formyl Peptide Receptor-Like 1 and -Like 2

AbstractBasophils circulate in the blood and are able to migrate into tissues at sites of inflammation. Urokinase plasminogen activator (uPA) binds a specific high affinity surface receptor (uPAR). The uPA-uPAR system is crucial for cell adhesion and migration, and tissue repair. We have investigated the presence and function of the uPA-uPAR system in human basophils. The expression of uPAR was found at both mRNA and protein levels. The receptor was expressed on the cell surface of basophils, in the intact and cleaved forms. Basophils did not express uPA at either the protein or mRNA level. uPA (10−12–10−9 M) and its uPAR-binding N-terminal fragment (ATF) were potent chemoattractants for basophils, but did not induce histamine or cytokine release. Inactivation of uPA enzymatic activity by di-isopropyl fluorophosphate did not affect its chemotactic activity. A polyclonal Ab against uPAR inhibited uPA-dependent basophil chemotaxis. The uPAR-derived peptide 84–95 (uPAR84–95) induced basophil chemotaxis. Basophils expressed mRNA for the formyl peptide receptors formyl peptide receptor (FPR), FPR-like 1 (FPRL1), and FPRL2. The FPR antagonist cyclosporin H prevented chemotaxis induced by FMLP, but not that induced by uPA and uPAR84–95. Incubation of basophils with low and high concentrations of FMLP, which desensitize FPR and FPRL1, respectively, but not FPRL2, slightly reduced the chemotactic response to uPA and uPAR84–95. In contrast, desensitization with WKYMVm, which also binds FPRL2, markedly inhibited the response to both molecules. Thus, uPA is a potent chemoattractant for basophils that seems to act through exposure of the chemotactic uPAR epitope uPAR84–95, which is an endogenous ligand for FPRL2 and FPRL1

Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management

Amyloidosis is a systemic disease characterized by extracellular deposits of insoluble amyloid in various tissues and organs. Cardiac amyloidosis is a frequent feature of the disease, causing a progressive, restrictive type of cardiomyopathy, and is associated with adverse clinical outcomes and increased mortality. The typical clinical presentation in patients with cardiac amyloidosis is heart failure (HF) with preserved ejection fraction. Most patients present with typical symptoms and signs of HF, such as exertional dyspnea, pretibial edema, pleural effusions and angina pectoris due to microcirculatory dysfunction. However, patients may also frequently encounter various arrhythmias, such as atrioventricular nodal block, atrial fibrillation and ventricular tachyarrhythmias. The management of arrhythmias in cardiac amyloidosis patients with drugs and devices is often a clinical challenge. Moreover, predictors of life-threatening arrhythmic events are not well defined. This review intends to give a deepened insight into the arrhythmic features of cardiac amyloidosis by discussing the pathogenesis of these arrhythmias, addressing the challenges in risk stratification and strategies for management in these patients