1,761 research outputs found

    Synthetic Routes to (+)-Cassiol and (-)-Cassioside

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    Factores de risco associados á transmissão de diarreia em crianças dos 6 meses aos 7 anos no bairro do Xipamanine

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    As diarreias continuam a ser em Moçambique e em muitos paises em desenvolvimento um dos problemas de Saúde pública mais importantes. São doenças transmissiveis não preveniveis por vacina eque ocorrem com frequencia de forma isolada ou associada à malnutrição e malaria causando elevadas taxas de mortalidade nos países em desenvolvimento. Para cada caso foi escolhido um controle constituido por indivíduos do mesmo sexo e idade que o casos, e residentes na mesma area, sem historia de dejecções liquidas nos ultimos 60 dias anteriores á data de recolha de dados. A área de estudo foi o Bairro do Xipamanine. Motivou a escolha desta zona o facto de este bairro ter durante anos consecutivos registado o maior número de casos das diarreias ocorridas na Cidade de Maputo. De acordo com dados da Direcção de Saude da Cidade do Maputo, em 1996, por exemplo, registaram-se 34.095 casos de diarrea nesta zona, dos quais 25.406 (75%) em crianças do 0-14 anos

    ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies

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    The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients’ outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients’ general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines

    Role of defects in the electronic properties of amorphous/crystalline Si interface

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    The mechanism determining the band alignment of the amorphous/crystalline Si heterostructures is addressed with direct atomistic simulations of the interface performed using a hierarchical combination of various computational schemes ranging from classical model-potential molecular dynamics to ab-initio methods. We found that in coordination defect-free samples the band alignment is almost vanishing and independent on interface details. In defect-rich samples, instead, the band alignment is sizeably different with respect to the defect-free case, but, remarkably, almost independent on the concentration of defects. We rationalize these findings within the theory of semiconductor interfaces.Comment: 4 pages in two-column format, 2 postscript figures include

    Autophagy Is a Defense Mechanism Inhibiting BCG and Mycobacterium tuberculosis Survival in Infected Macrophages

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    AbstractMycobacterium tuberculosis is an intracellular pathogen persisting within phagosomes through interference with phagolysosome biogenesis. Here we show that stimulation of autophagic pathways in macrophages causes mycobacterial phagosomes to mature into phagolysosomes. Physiological induction of autophagy or its pharmacological stimulation by rapamycin resulted in mycobacterial phagosome colocalization with the autophagy effector LC3, an elongation factor in autophagosome formation. Autophagy stimulation increased phagosomal colocalization with Beclin-1, a subunit of the phosphatidylinositol 3-kinase hVPS34, necessary for autophagy and a target for mycobacterial phagosome maturation arrest. Induction of autophagy suppressed intracellular survival of mycobacteria. IFN-γ induced autophagy in macrophages, and so did transfection with LRG-47, an effector of IFN-γ required for antimycobacterial action. These findings demonstrate that autophagic pathways can overcome the trafficking block imposed by M. tuberculosis. Autophagy, which is a hormonally, developmentally, and, as shown here, immunologically regulated process, represents an underappreciated innate defense mechanism for control of intracellular pathogens

    The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer

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    There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA<PRB) murine mammary carcinomas growing in BALB/c, GFP-BALB/c or nude mice, along with human T47D-YA and T47D-YB xenografts growing in immunocompromised NSG mice. MFP improved the therapeutic effects of suboptimal doses of Nab-paclitaxel or PEG-LD in murine and human carcinomas with higher levels of PRA than PRB. MFP induced tissue remodeling in PRA-overexpressing tumors, increasing the stromal/tumor cell ratio and the number of functional vessels. Accordingly, an increase in nanoparticles and drug accumulation was observed in stromal and tumor cells in MFP-treated tumors. We conclude that MFP induces an increase in vessels during tissue remodeling, favoring the selective accumulation of nanoparticles inside the tumors. We propose that antiprogestins have the potential to enhance the efficacy of chemotherapy in breast tumors with a high PRA/PRB ratio.Fil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologi­a "angel H. Roffo"; ArgentinaFil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Molinolo, Alfredo. National Institutes of Health. National Institute of Dental and Craniofacial Research. Oral and Phayngeal Cancer Branch; Estados UnidosFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

    Treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia lowers plasma levels of platelet-activating factor and its precursors: a combined metabolomic and lipidomic approach

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    13openInternationalItalian coauthor/editorIntroduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p < 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value < 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9iopenDi Minno, Alessandro; Orsini, Roberta Clara; Chiesa, Mattia; Cavalca, Viviana; Calcaterra, Ilenia; Tripaldella, Maria; Anesi, Andrea; Fiorelli, Susanna; Eligini, Sonia; Colombo, Gualtiero I; Tremoli, Elena; Porro, Benedetta; Di Minno, Matteo Nicola DarioDi Minno, A.; Orsini, R.C.; Chiesa, M.; Cavalca, V.; Calcaterra, I.; Tripaldella, M.; Anesi, A.; Fiorelli, S.; Eligini, S.; Colombo, G.I.; Tremoli, E.; Porro, B.; Di Minno, M.N.D

    Epidemiology of Candidemia in Latin America: A Laboratory-Based Survey

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    Background: the epidemiology of candidemia varies depending on the geographic region. Little is known about the epidemiology of candidemia in Latin America.Methods: We conducted a 24-month laboratory-based survey of candidemia in 20 centers of seven Latin American countries. Incidence rates were calculated and the epidemiology of candidemia was characterized.Results: Among 672 episodes of candidemia, 297 (44.2%) occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old and 19.6% in elderly patients. the overall incidence was 1.18 cases per 1,000 admissions, and varied across countries, with the highest incidence in Colombia and the lowest in Chile. Candida albicans (37.6%), C. parapsilosis (26.5%) and C. tropicalis (17.6%) were the leading agents, with great variability in species distribution in the different countries. Most isolates were highly susceptible to fluconazole, voriconazole, amphotericin B and anidulafungin. Fluconazole was the most frequent agent used as primary treatment (65.8%), and the overall 30-day survival was 59.3%.Conclusions: This first large epidemiologic study of candidemia in Latin America showed a high incidence of candidemia, high percentage of children, typical species distribution, with C. albicans, C. parapsilosis and C. tropicalis accounting for the majority of episodes, and low resistance rates.independent medical grant from Pfizer Inc.Univ Fed Rio de Janeiro, Univ Hosp, Rio de Janeiro, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilHosp Escuela Tegucigalpa, Tegucigalpa, HondurasHosp Clin Jose San Martin, Buenos Aires, DF, ArgentinaUniv Nacl Colombia, Dept Internal Med, Bogota, ColombiaPontificia Univ Catolica Ecuador, Fac Med, Hosp Vozandes, Quito, EcuadorHosp Vargas de Caracas, Caracas, VenezuelaCtr Med Caracas, Caracas, VenezuelaUniv Chile, Fac Med, Dept Pediat, Hosp Luis Calvo Mackenna, Santiago 7, ChileUniv Desarrollo, Clin Alemana, Dept Med, Infect Dis Unit, Santiago, ChileInst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, MexicoUniv Peruana Cayetano Heredia, Dept Med, Lima, PeruUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilWeb of Scienc

    Size Evolution of Ordered SiGe Islands Grown by Surface Thermal Diffusion on Pit-Patterned Si(100) Surface

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    The ordered growth of self-assembled SiGe islands by surface thermal diffusion in ultra high vacuum from a lithographically etched Ge stripe on pit-patterned Si(100) surface has been experimentally investigated. The total surface coverage of Ge strongly depends on the distance from the source stripe, as quantitatively verified by Scanning Auger Microscopy. The size distribution of the islands as a function of the Ge coverage has been studied by coupling atomic force microscopy scans with Auger spectro-microscopy data. Our observations are consistent with a physical scenario where island positioning is essentially driven by energetic factors, which predominate with respect to the local kinetics of diffusion, and the growth evolution mainly depends on the local density of Ge atoms
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