314 research outputs found
Capacitação em agroecologia na comunidade quilombola do Varzeão, Dr. Ulysses, Vale do Ribeira, PR.
O projeto "Assistência Técnica e Extensão Rural - ATER - e Capacitação em Agroecologia na Comunidade Quilombola do Varzeão, Dr. Ulysses, Vale do Ribeira" atua desde 2007 e procura, através da Agroecologia e dos seus princípios, contribuir com a organização das comunidades, estimulando o redesenho dos agroecossistemas. Os Quilombolas têm uma produção moldada através de métodos tradicionais e estão próximos dos princípios da Agroecologia. A comunidade remanescente de Quilombo do Varzeão se localiza em Dr. Ulysses e conta hoje com 19 famílias com um total de 56 pessoas com diversos problemas no que tange à sua situação social. O projeto surgiu por meio de contatos com as diversas organizações que atuam no Vale do Ribeira, isso desembocou em uma aproximação com a comunidade do Varzeão. Dessa forma, discutiu-se com a comunidade as demandas para um projeto de extensão, o que culminou na aprovação do projeto junto a Secretaria de Ciência e Tecnologia do Ensino Superior (SETI) - Universidade Sem Fronteiras e a Universidade Federal do Paraná (UFPR).Disponível também em: Cadernos de Agroecologia, V. 5, n.1, 2010
Teor de óleo essencial de Ocimum selloi Benth. sob diferentes doses de compostos orgânicos.
Em espécies bioativas, a aplicação de compostos orgânicos tem sido relacionada à produção de metabólitos secundários. No presente estudo, avaliou-se o efeito de diferentes doses de compostos orgânicos no teor de óleo essencial de alfavaca anisada, fornecendo bases científicas para agricultura orgânica. Em Curitiba-PR, ano de 2008, num delineamento em blocos ao acaso, com três repetições, doses (0, 0,85, 1,7 e 3 t.ha-1) de compostos estabilizados (A, B, C e D), elaborados com diferentes materiais orgânicos, foram utilizadas no cultivo de alfavaca anisada. O espaçamento utilizado em cultivo protegido irrigado foi de 0,5m entre linhas por 1,0m entre plantas. Aos seis meses de cultivo, amostras compostas de folhas foram coletadas e submetidas ao processo de hidrodestilação, por meio do aparelho do tipo Clevenger, para quantificação do óleo essencial. Em solo com acúmulo de matéria orgânica as doses e compostos avaliados não influenciaram o teor de óleo essencial de Ocimum selloi Beth.Disponível também em: Cadernos de Agroecologia, V. 5, n.1, 2010
Ralstonia pickettii—innocent bystander or a potential threat?
ABSTRACTRalstonia pickettii can be isolated from water, soil and plants, and can also form part of the commensal flora of the oral cavity and the upper respiratory tract of healthy individuals. R. pickettii is an infrequent pathogen, but can cause infections, mainly of the respiratory tract, in immunocompromised and cystic fibrosis patients. It can be isolated from a variety of clinical specimens, including sputum, blood, wound infections, urine, ear and nose swabs, and cerebrospinal fluid. Resistance can occur to ciprofloxacin, trimethoprim–sulphamethoxazole, piperacillin–tazobactam, imipenem–cilastatin and ceftazidime. Early detection of R. pickettii allows prompt appropriate antimicrobial therapy with a favourable outcome, but removal of infected indwelling devices is mandatory
Fast high-precision distance metrology using a pair of modulator-generated dual-color frequency combs
Improving the turnaround time of molecular profiling for advanced non-small cell lung cancer: Outcome of a new algorithm integrating multiple approaches
BACKGROUND
Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking. We have developed and implemented a new diagnostic algorithm to harmonize the molecular testing of NSCLC.
PATIENTS AND METHODS
In this retrospective analysis, we reviewed 119 patients diagnosed with NSCLC at the University Hospital Zurich. Tumor samples were analyzed using our standardized diagnostic algorithm: After the histological diagnosis was made, tissue samples were further analyzed by immunohistochemical stainings as well as the real-time PCR test Idylla™. Extracted DNA was further utilized for comprehensive genomic profiling (FoundationOne®CDx, F1CDx).
RESULTS
Out of the 119 patients were included in this study, 100 patients were diagnosed with non-squamous NSCLC (nsqNSCLC) and 19 with squamous NSCLC (sqNSCLC). The samples from the nsqNSCLC patients underwent testing by Idylla™ and were evaluated by immunohistochemistry (IHC). F1CDx analysis was run on 67 samples and 46 potentially actionable genomic alterations were detected. Ten patients received the indicated targeted treatment. The median time to test results was 4 days for the Idylla test, 5 days for IHC and 13 days for the F1CDx.
CONCLUSION
In patients with NSCLC, the implementation of a standardized molecular testing algorithm provided information on predictive markers for NSCLC within a few working days. The implementation of broader genomic profiling led to the identification of actionable targets, which would otherwise not have been discovered
Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany.
Talimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.
The aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.
Based on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36-95 years) treated with T-VEC during the period from May 2016 to January 2020.
88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1-65), an average of 11 doses (range: 1-36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).
This real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs
In vitro Efficacy of a Novel Guanosine-Analog Phosphonate
Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer
(NMSC), can transform into life-threatening cutaneous squamous cell carcinoma.
Current treatment is limited due to low complete clearance rates and asks for
novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be
an option. In order to enhance skin penetration, solid lipid nanoparticles
(SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.5 ±
0.1%. For improved preclinical evaluation, we combined tissue engineering with
clinically used keratin-18 quantification. Three doses of 10-3 mol/l OxBu,
dissolved in phosphate-buffered saline as well as loaded to SLN, were
effective on reconstructed NMSC. Tumour response and apoptosis induction were
evaluated by an increase in caspase-cleaved fragment of keratin-18, caspase-7
activation as well as by reduced expression of matrix metallopeptidase-2 and
Ki-67. OxBu efficacy was superior to equimolar 5-fluorouracil solution, and
thus the drug should be subjected to the next step in preclinical evaluation
Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?
Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab. This analysis was carried out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The median overall survival, defined from the treatment start date with the anti-CTLA-4. Abs-treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n = 62) was 10.12 months (95% CI 6.78-13.2) compared to 8.26 months (95% CI 6.02-19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). The median OS of NRAS mutated patients (n = 24) was 12.1 months and although was prolonged compared to the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) or BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach statistical significance (p = 0.56). 69 patients were able to complete 4 cycles of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK-inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based on our results, there is no difference in the median OS in patients treated with anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs
Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour
The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant
A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system
Lopes MW, Leal RB, Guarnieri R, et al. A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. TRANSLATIONAL PSYCHIATRY. 2016;6(12): e986.Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions
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