Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy.

The use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced. We recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry. We show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141 <sup>+</sup> DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased. Our study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets

Combining eutectic solvents and pressurized liquid extraction coupled in-line with solid-phase extraction to recover, purify and stabilize anthocyanins from Brazilian berry waste

Pressurized techniques are straightforward for high-scale applications and highly controllable, which seems an excellent strategy for recovering unstable natural compounds. In this work, the main advance was the development of a platform based on the pressurized liquid extraction coupled in-line with a solid-phase extraction step (PLE-SPE) combined with the use of eutectic mixtures as solvents to promote an efficient extraction and purification of natural pigments from food wastes. Eutectic mixtures, conventionally known as (deep) eutectic solvents – (D)ES, are combinations of two or more substances with a lower melting point than any of their components. (D)ES are often referred as “green solvents” because they can potentially be more environmentally friendly than other solvents, especially volatile organic solvents (VOSs). Overall, (D)ES have the potential to contribute to the achievement of several of the SDGs (especially 3, 13, and 14) through their positive impacts on health, environment, and sustainable production and consumption practices. Thus, in this work, (D)ES were used as solvents to valorize Brazilian berry waste (Plinia cauliflora). Anthocyanins are the biomass's main compounds of commercial interest, mainly for food and cosmetic applications. However, there are several technological issues regarding color control due to their high sensitivity to light, heat, oxygen, and pH variations. Thus, the data achieved in this work highlighted the high efficiency and low environmental footprint of the PLE-SPE-(D)ES platform developed. The success of the downstream process here developed was proved by the high extraction efficiency and the purity level of the anthocyanins obtained. Besides, thermal stability analysis was evaluated, demonstrating that (D)ES are not only solvents but also stabilizing agents, improving the shelf-life of the extracted colorants.publishe

Previsão probabilística de enchentes para uma pequena bacia hidrográfica do Pantanal.

O monitoramento para a previsão de cheias de pequenas bacias hidrográficas é de grande importância tendo em vista a relação dos recursos hídricos com a sociedade, pois pode garantir o uso sustentável às comunidades urbanas de cidades lindeiras à bacia. O rio Aquidauana está inserido na planície Pantaneira sendo considerado vulnerável à inundações, no entanto, falta de um sistema eficiente para previsões de cheias e inundações. Assim, este estudo propõe um sistema de previsão probalística de enchentes para a bacia do Rio Aquidauana. Para tanto foram utilizadas as redes neurais artificiais (RNAs) do tipo MultiLayer Perceptron (treinamento backpropagation) com parâmetros otimizados pelos Algoritmos Genéticos. A RNA foi treinada e avaliada com base em dados de chuva acumulada (mm) e nível de rio (cm) à montante entre os anos de 1995 a 2014. A previsão realizada foi de 1 a 5 dias, tendo como melhor desempenho o modelo para 1 dia de previsão, com resultado de coeficiente de determinação e erro quadrático médio de 0,93 e 30 (cm), respectivamente

New proposal of silver diamine fluoride use in arresting approximal caries: study protocol for a randomized controlled trial

Abstract\ud \ud Background\ud Approximal surfaces are a challenge to caries lesions control. Silver diamine fluoride (SDF) is a simple,low-cost and promisor intervention for arresting caries lesions, but it has never been tested on approximal surfaces. Our aim is to evaluate the efficacy and cost-efficacy of SDF in arresting initial lesions compared to resin infiltration and exclusively flossing (control group). Our second aim is to assess discomfort and satisfaction regarding interventions.\ud \ud \ud Methods/design\ud This is a randomized clinical trial, double-blinded, placebo-controlled study. Children/adolescents presenting at least one approximal initial caries lesion in primary molars/permanent premolars and molars will be included. Surfaces with advanced dentine lesions identified by radiography and participants who refuse to participate or present negative behaviors will be excluded. A minimum sample size of 504 surfaces will be required for each subgroup. Individuals will be randomly allocated in three groups of interventions: SDF, resin infiltration, and control group. Depending on the allocation, the patients will receive the active treatment and respective placebo therapies. All patients will be oriented to daily flossing the included surfaces. Our primary outcome will be caries progression by clinical and radiographic examinations. Appointments will be timed and costs of materials will be considered to calculate cost-efficacy. Patient discomfort will be assessed after interventions. Parent and patient satisfaction with the treatment will be collected after treatment and in the last follow-up visit. Individuals will be assessed at 1 and 3 months after treatment to evaluate dental biofilm and at 6, 12, and 24 months to assess caries progression by visual examination and/or radiography. Multilevel analyses will be used to verify if the type of treatment influenced on the tested outcomes. Costs will be compared and analyses of cost-efficacy will be performed. Poisson analysis will test the association between intervention and reported discomfort and satisfaction.\ud \ud \ud Discussion\ud Our hypothesis is that SDF is the most cost-efficacious option from all tested interventions. If our hypothesis is confirmed, the use of SDF in private and public contexts could represent an easier and effective option in the treatment of enamel approximal caries in children/adolescents.\ud \ud \ud Trial registration\ud ClinicalTrials.gov (\ud NCT01477385\ud \ud ), Initial release: 11/16/2011: last update: 06/02/2014.Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (Protocols 2012/50716-0 and 2014/00271-7)CNPQCape

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Standardization of the energy performance of photovoltaic modules in real operating conditions

The performance of a PV module at STC [1] is a useful indicator for comparing the peak performance of different module types, but on its own is not sufficient to accurately predict how much energy a module will deliver in the field when subjected to a wide range of real operating conditions [2]. An Energy Rating approach has to be preferred for that aim. It is currently under development the standard series IEC 61853 on Energy Rating, for which only part 1 [3] has been issued. It describes methods to characterize the module performance as a function of irradiance and temperature. The reproducibility of the power matrix measurements obtained by the three different methods specified in the standard, namely: under natural sunlight using a tracking system; under natural sunlight without tracker; and a large area pulsed solar simulator of Class AAA were evaluated and discussed [4,5]. The work here presented is focused on the second method listed above, which explores the real working conditions for a PV device and therefore it represents the situation where Energy Rating procedures are expected to give the largest deviations from the STC predictions. The system for continuous monitoring of module performances, already implemented at ESTI, has been recently replaced with a new system having a number of improvements described in the following. The two system results have been compared showing a discrete compatibility. The two power matrices are then merged together using a weighted average and compared to those acquired with the other two remaining “ideal” systems. An interesting tendency seems to come up from this comparison, making the power rating under real operating conditions an essential procedure for energy rating purposes

Standardization of the energy performance of photovoltaic modules in real operating conditions

The performance of a PV module at STC [1] is a useful indicator for comparing the peak performance of different module types, but on its own is not sufficient to accurately predict how much energy a module will deliver in the field when subjected to a wide range of real operating conditions [2]. An Energy Rating approach has to be preferred for that aim. It is currently under development the standard series IEC 61853 on Energy Rating, for which only part 1 [3] has been issued. It describes methods to characterize the module performance as a function of irradiance and temperature. The reproducibility of the power matrix measurements obtained by the three different methods specified in the standard, namely: under natural sunlight using a tracking system; under natural sunlight without tracker; and a large area pulsed solar simulator of Class AAA were evaluated and discussed [4,5]. The work here presented is focused on the second method listed above, which explores the real working conditions for a PV device and therefore it represents the situation where Energy Rating procedures are expected to give the largest deviations from the STC predictions. The system for continuous monitoring of module performances, already implemented at ESTI, has been recently replaced with a new system having a number of improvements described in the following. The two system results have been compared showing a discrete compatibility. The two power matrices are then merged together using a weighted average and compared to those acquired with the other two remaining “ideal” systems. An interesting tendency seems to come up from this comparison, making the power rating under real operating conditions an essential procedure for energy rating purposes