Comparative study between wet and dry etching of silicon for microchannels fabrication

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOIn this work we present a comparative study of two processes for the fabrication of an array of microchannels for microfluidics applications, based on integrated-circuit technology process steps, such as lithography and dry etching. Two different methods were investigated in order to study the resulting microstructures: wet and dry deep etching of silicon substrate. The typical etching depth necessary to the target application is 50 mu m.1093015FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09509-112. Conference on Advanced Fabrication Technologies for Micro/Nano Optics and Photonics3 a 5 de Fevereiro de 2019San Francisco, CA, Estados UnidosSPIE; Nanoscribe Gmb

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl prednisolone in male inflammatory arthropathies: a 12-month open randomized pilot study.

Objective. To evaluate: (i) a correct equivalence ratio of clinical efficacy between low-dose deflazacort (DFZ) and methyl prednisolone (MP); and (ii) bone metabolic effects of low-dose DFZ and MP in the treatment of male RA and PsA. Methods. A total of 21 male patients with active RA or PsA, naive to steroid treatment were chosen for the study. Group I: 10 patients treated for 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD. Group II: 11 patients treated for 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD. At day 0, 90, 180, 240 and 360 evaluation of ACR improvement criteria; a blood sample for total and bone-specific ALP, calcium, phosphorus, PTH, SHBG, estradiol, ACTH, osteocalcin, LH, OPG; a sample of urine for calcium, phosphorus, creatinine and DPD. Results. 13/21 patients (6/10 Group I; 7/11 Group II) reached ACR 20 at 6 months; 14/21 (7/10 Group I, 7/10 Group II) at 12 months. Only at the third month we observed in Group II vs Group I a reduction of OPG (24% vs 6%, P= n.s.); ALP (P < 0.001) and osteocalcin (P = 0.006) decreased in both groups from the third month; DPD decreased in both groups only from the sixth month (P = 0.002). Conclusions. The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible

Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H2S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic (mdx) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H2S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H2S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H2S-donors for novel and safe adjuvant therapy to treat symptoms of DMD

Caracterização de rebanhos em sistemas de produção orgânica de leite no Sudeste do Brasil.

Este estudo visou conhecer os rebanhos em sistemas orgânicos de produção de leite localizados na região Sudeste do país. Os dados foram obtidos pela observação e aplicação presenciais de questionário a amostra de 10 produtores para obtenção de detalhes sobre o recurso genético usado, os métodos de reprodução adotados, a realização de escrita zootécnica e aspectos produtivos de suas propriedades. Em média, as propriedades visitadas possuíam rebanhos com 55 vacas em lactação, mantidas predominantemente a pasto, e produção diária de 14 litros de leite. Porém, na maioria dos rebanhos não se realizava o controle leiteiro individual e outras anotações zootécnicas, o que resulta em dificuldades na tomada de decisões de manejo e melhoramento animal na propriedade. Além disso, nesses rebanhos, ficou destacada a maior frequência de animais mestiços, com diferentes composições raciais, e o uso de inseminação artificial como principal ferramenta reprodutiva. Todavia, os rebanhos são muito despadronizados morfológica e produtivamente, indicando a necessidade de adoção de práticas de manejo reprodutivo focadas em estratégias de melhoramento que permitam não apenas o ganho em produção individual de leite, mas também em outras características economicamente importantes. Para que se alcance um melhor desempenho produtivo e se possa proceder à seleção de animais nos rebanhos, faz-se necessário o planejamento dos cruzamentos, a adoção de biotécnicas reprodutivas e a realização de escrita zootécnica