Targeting the mitochondrial respiratory chain of Cryptococcus through antifungal chemosensitization: a model for control of non-fermentative pathogens.

Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC) inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular MRC, octyl gallate (OG) or 2,3-dihydroxybenzaldehyde (2,3-DHBA), phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to pyraclostrobin (PCS; an inhibitor of complex III of MRC). The cryptococci were more susceptible to the chemosensitization (i.e., PCS + OG or 2,3-DHBA) than the Candida with all Cryptococcus strains tested being sensitive to this chemosensitization. Alternatively, only few of the Candida strains showed sensitivity. OG possessed higher chemosensitizing potency than 2,3-DHBA, where the concentration of OG required with the drug to achieve chemosensitizing synergism was much lower than that required of 2,3-DHBA. Bioassays with gene deletion mutants of the model yeast Saccharomyces cerevisiae showed that OG or 2,3-DHBA affect different cellular targets. These assays revealed mitochondrial superoxide dismutase or glutathione homeostasis plays a relatively greater role in fungal tolerance to 2,3-DHBA or OG, respectively. These findings show that application of chemosensitizing compounds that augment MRC debilitation is a promising strategy to antifungal control against yeast pathogens.publishersversionpublishe

ADDON+ network : tackling the downfall of the turkish market

The Case Study presented in this Thesis addresses the path of a small Portuguese architecture firm called ADDON+ specialized in designing projects for large shopping centers. Its operations were focused on Turkey, and the company faced a big challenge when its main market collapsed. The reason for the collapse was the political instability felt in Turkey around 2016, that led to major economic problems and a depreciation of their currency. The Case Study allows for discussing topics such as risk management, competitors’ behavior, market structure, internationalization problems, differentiation and positioning. The Master Thesis includes a Literature Review of subjects related to the main issues of the Case and a Teaching Note to help instructors prepare for the in-class discussion of the Case. The main conclusions can be summed up as the necessity for managers to be aware of changes in the market and the need to diversify income sources, so that the exposure to negative industry characteristics or to external factors is limited.O Case Study apresentado nesta tese aborda o percurso de uma pequena empresa de arquitetura portuguesa chamada ADDON+ Network que era especializada em projetos para centros comerciais. Suas operações estavam focadas na Turquia e foi lá que a empresa enfrentou um grande desafio quando seu principal mercado entrou em colapso. Este colapso foi causado por problemas de instabilidade política sentidos na Turquia por volta de 2016, o que levou a problemas económicos e a uma desvalorização acelerada da moeda turca. O Case Study permite discutir temas como gestão de riscos, comportamento dos competidores, estrutura de mercado, assim como problemas de internacionalização, diferenciação e posicionamento. Esta Dissertação de Mestrado inclui uma Revisão da Literatura de assuntos relacionados com as principais questões do Caso e da Teaching Note de maneira a ajudar os professores a se prepararem para a discussão do Caso em aula. As principais conclusões que podem ser tiradas são a necessidade de os gestores estarem atentos às mudanças do mercado e também a necessidade de diversificar as fontes de rendimento, de modo que a exposição às características negativas do setor ou até a fatores externos seja limitada

Dilemas e aporias subjacentes aos processos de implementação da Lei 10.639/2003

Este artigo reflete sobre os dilemas e as aporias subjacentes aos processos de implementação da Lei 10.639/2003 reafirmados na pesquisa “Práticas Pedagógicas de Trabalho com Relações Étnico-Raciais na Perspectiva da Lei 10.639/2003” na região NE II, envolvendo os Estados de Pernambuco, Paraíba, Alagoas, Piauí e Rio Grande do Norte, realizada em 2009 pela UNESCO e MEC – Ministério da Educação – e coordenada pelo Programa de Ações Afirmativas da UFMG. A pesquisa foi de cunho qualitativo, utilizou procedimentos metodológicos de análise documental, entrevistas e observações de campo. A perspectiva teórica que referendou as análises foi o transculturalismo crítico, em fase de constituição. Os autores que têm referendado essa perspectiva são Santos (2003), Santana (2000), Assmann (1994), Benjamin (1994), Hall (2003), McLaren (1993), Munanga (1996a, 1996b, 1996c), Tinhorão (1991) e Todorov (1999). Os resultados do trabalho indicam que a Educação das Relações Étnico-Raciais só superará seus dilemas e aporias fundamentais quando a educação escolarizada incorporar efetivamente o princípio da diversidade cultural humana enquanto eixo orientador das práticas educativas escolarizadas. O trabalhou também apontou para a necessidade de o Estado desenvolver programas estruturadores que articulem os processos de formação inicial e continuada de professoras/es com os Núcleos de Estudos Afro-Brasileiros e os Grupos de Trabalho das Secretarias Estaduais e Municipais de Educação que tratam da Educação das Relações Étnico-Raciais

Osteopatia hipertrófica secundária a osteossarcoma condroblástico extraesquelético em um cão

Background: hypertrophic osteopathy is a periosteum disturb characterized by diffuse new bone formation which leads to significant thickening and deformity of members. Secondary in nature, it usually follows large pulmonary lesions such as abscesses and neoplasms. Extraskeletal osteosarcomas are rare and extremely malignant mesenchymal neoplasms. They comprise approximately 1% of all domestic animals’ osteosarcomas and develop in the absence of a primary bone lesion. The aim of this paper was to describe a case of hypertrophic osteopathy, involving joints and upper limbs bones including ilium, secondary to a mediastinal chondroblastic osteosarcoma with pulmonary metastasis.Case: A 10-year-old spayed female mixed breed dog, weighing 9 kg, was presented with painful limbs, lameness, hind limbs swelling and a four-month history of weight loss. Radiographic examination revealed bilateral and asymmetric periosteal reactions on diaphyseal and/or epiphyseal areas of all proximal phalanges; metacarpal, metatarsal, carpal and tarsal bones; radius; ulna; tibia; fibula; humerus; femur and right ilium. An increased soft tissue radiopacity was noted on the lateral side of the right knee joint. Thoracic radiographies and ultrasonography suggested the presence of a 5-cm neoplasm or abscess in the left caudal lung lobe. At necropsy, the lobe showed a firm and solid, oval white mass measuring 5.2 x 2.9 cm. Another mass was found in the caudal mediastinum, near the diaphragm, with same color and more irregular aspect, measuring 3.3 cm of diameter. Intense periosteal new-bone formation was seen in the entire length of the four limbs bones, characterized by thickening of the bone surface and formation of irregular trabeculae perpendicular to the cortex. Significant swelling and thickening of the joint capsule was noted in the right knee. There was no microbial growth on aerobic or anaerobic cultures from the masses samples sent to culture. Histopathological examination showed areas of chondroid differentiation, osteoidtissue formation and cell morphology suggestive of chondroblastic osteosarcoma in mediastinal region, with invasion and involvement of the diaphragm and lungs. The analyzed bone fragment had large foci of tissue compaction, peritrabecular bleeding and mineralization of osteoid tissue, permeated by plasma cells and typical lymphocytes.Discussion: Although hypertrophic osteopathy is often characterized as a disease which affects the diaphysis of distal long bones, this case presented a proximal progression of the disease. There was an unusual involvement of joints and ilium, which reinforces the importance of radiographic evaluation of these regions. Further studies on the pathogenesis of the syndrome are required, as its exact mechanisms remain obscure. It is suggested that the term hypertrophic osteoarthropathy should not be consider a misnomer since joint involvement is not exclusive of human form of the disease. Mediastinal masses are important cause of hypertrophic osteopathy. However, this is the first paper the authors are aware of that reports the occurrence of hypertrophic osteopathy secondary to mediastinal osteosarcoma. Finally, although rare, extra skeletal osteosarcoma should be considered in the differential diagnosis of intrathoracic masses in dogs with hypertrophic osteopathy. Timely diagnosis of hypertrophic osteopathy, whose signs of lameness and painful limbs draw the owner’s attention, may favor the diagnosis of severe concomitant diseases

Enhancement of Commercial Antifungal Agents by Kojic Acid.

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Abdominal hernia repair with bovine pericardium seeded with mesenchymal stem cells in Wistar rats

Background: Biological membranes demonstrate superiority over synthetic ones for its biocompatibility and strength in the reduction of abdominal hernias. Recents tissue engineering researches add mesenchymal stem cells to biological membranes with the purpose of obtaining additional cellular proliferation and consequent muscle regeneration, using biological membranes as cellular scaffolds. This article aimed to study the infl uence of mesenchymal stem cells in muscle regeneration in abdominal hernias, reduced with biological membranes. Materials, Methods & Results: Adult Wistar rats underwent abdominal hernia-inducing. They were divided into two groups as to the form of treatment for the reduction of hernia: stem cells associated with biological membranes or only biological membranes. After the treatment the macro and microscopic reviews were carried out in days seven, 14 and 60 postoperatively. Preparation of bovine pericardium with glycerin 98% presented effi ciency in decellularization and conservation, maintaining its strength and avoiding bacterial growth. The mesenchymal stem cells obtained from bone marrow of adult Wistar rats, had capacity of proliferation. The majority of the cells was positive for the expression of surface antigens CD44, CD29 and CD99 and was negative for CD 34. In the differentiation trials, the same cells were able to differentiate into adipocytes and osteocytes. With 24 h from co-cultivating adhesion of mesenchymal stem cells in the membranes was observed. There was no foreign body reaction or contamination of surgical wounds and there was intense postoperative neovascularization on seven days. All animals presented omentum adherence, but no adherence to other organs. There was no statistically difference for the different times in macroscopic assessment: deposition of fi brous tissue, implant integration. The same occurred with the microscopic evaluations between the different treatment groups. The groups of immediate and later repair presented different responses to treatment. Discussion: The use of rats as animal model was satisfactory, being suitable for surgical procedures and assessments of the abdominal cavity. The different results obtained between groups of immediate repair and late repair corroborate with the idea that there is difference between induction and repair models in the same surgery or in different surgeries with the time interval between the two, suggesting the need for methodologies that simulate the hernias chronicity. The cells used were classifi ed as mesenchymal stem cells, because it met all the criteria of Mesenchymal and Tissue Stem Cell Committee of the International Society of Celullar Therapy. The membranes conserved with glycerin 98% demonstrated biocompatibility, because there was no rejection or necrosis, infection or exacerbated infl ammation. However the muscle regeneration was not obtained over the membranes - and the methodological difference in other latest experiments about the membranes decellularization and the co-cultivating - can leads to conclusion that the cells attached to membranes were insuffi cient in number to obtain the desired result. These results suggest the need of new research studies or co-cultivating times and decellularization methods of bovine pericardium for association with mesenchymal stem cells

Reuma.pt/vasculitis - the Portuguese vasculitis registry

BACKGROUND: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development. RESULTS: A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet's disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported. CONCLUSIONS: Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.publishersversionpublishe

Trajetórias da Educomunicação nas Políticas Públicas e a Formação de seus Profissionais

Esta obra é composta com os trabalhos apresentados no primeiro subtema, TRAJETÓRIA – Educação para a Comunicação como Política pública, nas perspectivas da Educomunicação e da Mídia-Educação, do II Congresso Internacional de Comunicação e Educação. Os artigos pretendem propiciar trocas de informações e produzir reflexões com os leitores sobre os caminhos percorridos, e ainda a percorrer, tendo como meta a expansão e a legitimação das práticas educomunicativas e/ou mídia-educativas como política pública para o atendimento à formação de crianças, adolescentes, jovens e adultos, no Brasil e no mundo

Educomunicação, Transformação Social e Desenvolvimento Sustentável

Esta publicação apresenta os principais trabalhos dos GTs do II Congresso Internacional de Comunicação e Educação nos temas Transformação social, com os artigos que abordam principalmente Educomunicação e/ou Mídia-Educação, no contexto de políticas de diversidade, inclusão e equidade; e, em Desenvolvimento Sustentável os artigos que abordam os avanços da relação comunicação/educação no contexto da educação ambiental e desenvolvimento sustentável

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700