Genome-Wide Analysis of Genetic Changes in Intestinal-Type Sinonasal Adenocarcinoma

[Resumo] Nos nossos dias, à educação é pedida uma actuação, dentro e fora do sistema educativo formal, capaz de dotar os indivíduos de conhecimentos, competências e técnicas que lhes permitam responder positivamente aos desafios de uma sociedade em transformação. Neste contexto, a intervenção comunitária surge como um novo campo educativo, uma proposta de trabalho em educação que se caracteriza por partir dos problemas e contar com a participação das populações tornandose elas próprias as protagonistas da mudança social.O nosso breve ensaio tem como objectivo apresentar um projecto de intervenção comunitária que desenvolvemos no contexto das dinâmicas educativas realizadas no âmbito da sociedade civil alargada.[Abstract] Nowadays, it is asked to education an action, in and out of de formal educational system, capable of endowing the individuals of knowledges, skills and technics that allow them to answer positively to the challanges of a society in transformation.In this context, the communitary intervention emerges as a new educative field, a work proposal in education that characterizes itself by starting from problems and relies on the participation of populations, becoming themselves the main characters of the social change.Our brief essay has the purpose of presenting a communitary intervention project that we developed in the context of the educative dynamics accomplished in the enlarged civil society

Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study

HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT

Brain tumor acidification using drugs simultaneously targeting multiple pH regulatory mechanisms

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Introduction: Non-invasively distinguishing aggressive from non-aggressive brain tumors is an important clinical challenge. Intracellular pH (pHi) regulation is essential for normal cell function and is normally maintained within a narrow range. Cancer cells are characterized by a reversed intracellular to extracellular pH gradient, compared to healthy cells, that is maintained by several distinct mechanisms. Previous studies have demonstrated acute pH modulation in glioblastoma detectable by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) after blocking individual pH regulatory mechanisms. The purpose of the current study was to simultaneously block five pH regulatory mechanisms while also providing glucose as an energy substrate. We hypothesized that this approach would increase the acute pH modulation effect allowing the identification of aggressive cancer. Methods: Using a 9.4 T MRI scanner, CEST spectra were acquired sensitive to pHi using amine/amide concentration independent detection (AACID). Twelve mice were scanned approximately 11 ± 1 days after implanting 105 U87 human glioblastoma multiforme cells in the brain, before and after intraperitoneal injection of a combination of five drugs (quercetin, cariporide, dichloroacetate, acetazolamide, and pantoprazole) with and without glucose. Results: Two hours after combination drug injection there was a significant 0.1 ± 0.03 increase in tumor AACID value corresponding to a 0.4 decrease in pHi. After injecting the drug combination with glucose the AACID value increased by 0.18 ± 0.03 corresponding to a 0.72 decrease in pHi. AACID values were also slightly increased in contralateral tissue. Conclusions: The combined drug treatment with glucose produced a large acute CEST MRI contrast indicating tumor acidification, which could be used to help localize brain cancer and monitor tumor response to chemotherapy