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Con el objetivo de contar con una herramienta que permita caracterizar con exactitud la interaccion entre la red electrica y los sistemas fotovoltaicos conectados a red se desarrollo un analizador de redes monofasico clase A conforme a las normas IEC 61000-4-7:2003 e IEC 61000-4-30:2003. El instrumento fue caracterizado mediante contraste con un instrumento de gran exactitud en condiciones reales de operacion. Los resultados obtenidos en este ensayo mostraron que las diferencias entre los valores de los parametros de potencia y los parametros de distorsion son menores al error propio del instrumento empleado como referencia, excepto en la determinacion del valor de distorsion armonica total en la senal de corriente. Un estudio pormenorizado de esta cuestion demostro que la diferencia tiene su origen en la metodologia de medicion empleada por cada instrumento que arroja resultados diferentes ante una caracteristica de operacion propia de los inversores para conexion a red.

A high-carbohydrate diet (HCD) is a well-established experimental model of accelerated liver fatty acid (FA) deposition and inflammation. In this study, we evaluated whether canola oil can prevent these physiopathological changes. We evaluated hepatic FA accumulation and inflammation in mice fed with a HCD (72.1% carbohydrates) and either canola oil (C group) or soybean oil (S group) as a lipid source for 0, 7, 14, 28, or 56 days. Liver FA compositions were analyzed by gas chromatography. The mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was measured as an indicator of lipogenesis. The mRNA expression of F4/80, tumor necrosis factor-&alpha, (TNF-&alpha, ), interleukin (IL)-1&beta, IL-6, and IL-10, as mediators of liver inflammation, were also measured. The C group stored less n-6 polyunsaturated FAs (n-6 PUFAs) and had more intense lipid deposition of monounsaturated FAs (MUFAs), n-3 PUFAs, and total FAs. The C group also showed higher ACC1 expression. Moreover, on day 56, the C group showed higher expressions of the inflammatory genes F4/80, TNF-&alpha, IL-1&beta, and IL-6, as well as the anti-inflammatory IL-10. In conclusion, a diet containing canola oil as a lipid source does not prevent the fatty acid accumulation and inflammation induced by a HCD.

An amendment to this paper has been published and can be accessed via the original article.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.

The present work addresses the inclusion and accessibility of people with visual or hearing disabilities in paleontology museum spaces, in order to provide access to scientific culture. The 2010 Demographic Census shows that 23.9% of the Brazilian population has some type of disability, and of this percentage, few attend scientific cultural spaces, because they do not know how the service and access will be. Thus, the aim is to adapt and reorganize the paleontological exhibition room at the Professor Walter Ilha Paleontological and Archaeological Museum, in the municipality of São Pedro do Sul, Rio Grande do Sul. For this, the methodology consists on the application of assistive technology (audio description and translation in Libras) accessed via QR Code, labels and information panels in enlarged font, 3D printed Braille labels. This work is important, because the number of museums with paleontological exhibitions, which are accessible and included, is reduced. This proposal will contribute to the protection and dissemination of the local paleontological heritage, in addition to human and cultural heritage valorization. O presente trabalho aborda a inclusão e acessibilidade de pessoas com deficiência visual ou auditiva em espaços museais de paleontologia, a fim de propiciar o acesso à cultura científica. O Censo Demográfico de 2010 demostra que 23,9% da população brasileira possui algum tipo de deficiência, e desta porcentagem, poucos frequentam espaços culturais científicos, por não saberem como será o atendimento e acesso. Desta forma, objetiva-se adequação e reorganização da sala de exposição paleontológica do Museu Paleontológico e Arqueológico Professor Walter Ilha, no município de São Pedro do Sul, Rio Grande do Sul. Para isto, a metodologia constitui-se na aplicação de tecnologia assistiva (audiodescrição e tradução em Libras) acessadas através de QR Code, etiquetas e painéis informativos em fonte ampliada, etiquetas em Braille impressas em 3D. Este trabalho é importante, pois, o número de museus com exposições paleontológicas, que são acessíveis e inclusos é reduzido. Entende-se que esta proposta contribuirá com a proteção e divulgação do patrimônio paleontológico local, além da valorização humana e patrimonial.

Determination of seed-maturation indicators enables the identification of the ideal moment for harvest to achieve the best production and conservation potential. Our objective here was to evaluate some physical and physiological changes of crambe (Crambe abyssinica Hochst) seeds as possible indicators of seed maturation. Crambe flowering was monitored in Dourados, Mato Grosso do Sul, Brazil. Plants were tagged, and 13, 22, 26, and 28 days after the initiation of flowering, the seeds were collected and following physical attributes evaluated: length, diameter, total mass, dry matter and water content. Physiological quality of the seeds was assessed using the germination test, by registering the percentage of normal seedlings and dormant seeds, immediately after each harvest, and again after six months of storage. The water-absorption curves were characterized as a function the seed-development stages. All physical attributes were observed to increase because of the accumulation of reserve substances during seed development, except for water content, which gradually decreased from 72.2% at the start of development to 29.5% at maturity. At 28 days after anthesis the germination percentage of crambe seeds at physiological maturity was only 17%, indicating that they became dormant while maturing. However, seed germination rate was 89% after six months of storage, indicating that dormancy was almost fully overcome after this period. Determination of seed-maturation indicators enables the identification of the ideal moment for harvest to achieve the best production and conservation potential. Our objective here was to evaluate some physical and physiological changes of crambe (Crambe abyssinica Hochst) seeds as possible indicators of seed maturation. Crambe flowering was monitored in Dourados, Mato Grosso do Sul, Brazil. Plants were tagged, and 13, 22, 26, and 28 days after the initiation of flowering, the seeds were collected and following physical attributes evaluated: length, diameter, total mass, dry matter and water content. Physiological quality of the seeds was assessed using the germination test, by registering the percentage of normal seedlings and dormant seeds, immediately after each harvest, and again after six months of storage. The water-absorption curves were characterized as a function the seed-development stages. All physical attributes were observed to increase because of the accumulation of reserve substances during seed development, except for water content, which gradually decreased from 72.2% at the start of development to 29.5% at maturity. At 28 days after anthesis the germination percentage of crambe seeds at physiological maturity was only 17%, indicating that they became dormant while maturing. However, seed germination rate was 89% after six months of storage, indicating that dormancy was almost fully overcome after this period.

Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak.

Population growth directly affects the industrial production sector, as well as the quantities of waste generated in this sector. Diatomite is a typical example of such industrial waste and is used for the filtration of various products. With the aim of increasing its value, the present study employs this residue, following its usage in beer filtration, as a silicon source for the synthesis of zeolites. Two synthetic routes are used, namely, hydrothermal treatment with and without a pre-treatment step in a conventional microwave for 3–24 h. The results of the compositional and morphological characterization show that the use of a few minutes of microwave radiation reduces the process of zeolite synthesis to 15 h compared to the synthesis without pre-treatment, as well as reducing the production costs. The efficiency of microwave radiation is assessed with regards to solubilizing the residue, the possibility of employing a device of conventional use and the possibility of putting to use the diatomite residue, turning it into a versatile material that can be applied in several areas and process, such as industrial catalysts, the adsorption of environmental pollutants (ions and molecules) and water treatment via ion-exchange resins.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known toinhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses onthe role of age-related processes in myelopoiesis.

Mature hair cells transduce information over a wide range of stimulus intensities and frequencies for prolonged periods of time. The efficiency of such a demanding task is reflected in the characteristics of exocytosis at their specialized presynaptic ribbons. Ribbons are electron‐dense structures able to tether a large number of releasable vesicles allowing them to maintain high rates of vesicle release. Calcium entry through rapidly activating, non‐inactivating CaV1.3 (L‐type) Ca2+ channels in response to cell depolarization causes a local increase in Ca2+ at the ribbon synapses, which is detected by the exocytotic Ca2+ sensors. The Ca2+ dependence of vesicle exocytosis at mammalian vestibular hair cell (VHC) ribbon synapses is believed to be linear, similar to that observed in mature cochlear inner hair cells (IHCs). The linear relation has been shown to correlate with the presence of the Ca2+ sensor synaptotagmin‐4 (Syt‐4). Therefore, we studied the exocytotic Ca2+ dependence, and the release kinetics of different vesicle pool populations, in Type II VHCs of control and Syt‐4 knockout mice using patch‐clamp capacitance measurements, under physiological recording conditions. We found that exocytosis in mature control and knockout Type II VHCs displayed a high‐order dependence on Ca2+ entry, rather than the linear relation previously observed. Consistent with this finding, the Ca2+ dependence and release kinetics of the ready releasable pool (RRP) of vesicles were not affected by an absence of Syt‐4. However, we did find that Syt‐4 could play a role in regulating the release of the secondary releasable pool (SRP) in these cells. Our findings show that the coupling between Ca2+ influx and neurotransmitter release at mature Type II VHC ribbon synapses is faithfully described by a nonlinear relation that is likely to be more appropriate for the accurate encoding of low‐frequency vestibular information, consistent with that observed at low‐frequency mammalian auditory receptors., Here we show that the coupling between neurotransmitter release at the ribbon synapses of mature vestibular Type II hair cells display a high‐order dependence on calcium influx. The calcium dependence was not affected by an absence of the calcium‐sensing synaptic molecule synaptotagmin‐4, which has been shown to be involved in establishing the linear calcium dependence of high‐frequency auditory hair cells. Our findings suggest that a nonlinear exocytotic calcium dependence in vestibular hair cells is likely to be more appropriate for the accurate encoding of low‐frequency vestibular information.

Diante das inovações do ensino superior, questionamos: como compreender a atuação, os papéis, as atitudes de professores e alunos, sujeitos do processo de aprendizagem no ensino superior? Objetivando buscar responder a este questionamento, analisamos dois aspectos: o resgate do processo de aprendizagem e a valorização da relação adulta entre professor e aluno, por meio da abordagem qualitativa, empregando o estudo bibliográfico e um levantamento de nossas experiências docentes no ensino superior nas últimas décadas, publicadas em artigos e livros. Dadas las innovaciones de la educación superior, nos preguntamos: ¿cómo entender el desempeño, los roles, las actitudes de los profesores y estudiantes, las asignaturas de los procesos de innovación en la educación superior? Con el objetivo de responder a esta pregunta, analizamos dos aspectos: el rescate del proceso de aprendizaje y la valorización de la relación de adultos entre profesor y alumno, a través del enfoque cualitativo, empleando el estudio bibliográfico y una encuesta de nuestras experiencias docentes en educación superior en las últimas décadas, publicadas en artículos y libros. Given the innovations of university education, we question: how to understand the performance, roles, attitudes of teachers and students, the subjects of innovation processes in higher education? Aiming to answer this question, we analyzed two aspects: the rescue of the learning process and the valorization of the adult relationship between teacher and student, through the qualitative approach, employing the bibliographic study and a survey of our teaching experiences in higher education in recent decades, published in articles and books.

Desde o início deste século, a universidade brasileira se vê envolvida em inovações que afetam os paradigmas curriculares, a dinamização das aulas universitárias através de metodologias ativas, a chegada do aluno que, no dizer de Veen e Vrakking (2009) se apresenta como um “homo zappiens” conectado com inúmeros grupos de WhatsApp, Facebook, Instagram. Neste cenário, um desafio para o docente: como agir de modo eficaz junto aos alunos para que estes se formem profissionais competentes para o século XXI? Este é o objetivo deste artigo: responder a esse desafio, nos baseando em estudos teóricos sobre inovações no ensino superior, em nossas experiências de docência nas últimas décadas, em orientações de pesquisas de mestrado e doutorado defendidas sobre projetos curriculares inovadores e formação de professores para agirem em tais projetos. As trilhas percorridas se entrelaçaram com estudos teóricos de autores como Sacristán (1998), Cunha (1998, 2009), Arroyo (2000), Zabalza (2004), Perrenoud (2013); com o exercício de práticas docentes e pesquisas de campo realizadas e publicadas em artigos e livros por Masetto (1992, 2010a, 2010b, 2018) e por Gaeta e Masetto, (2013), apresentadas em trabalhos e congressos nacionais e internacionais. Quatro trilhas comporão nossas reflexões e análises: a primeira, voltada para a necessária abertura do professor para as inovações atuais no ensino superior brasileiro; a segunda, resgatando a característica da profissionalidade na atuação docente; a terceira destacando o trabalho em equipe do corpo docente e, a quarta, evidenciando a construção de um agir docente competente em situações de sala de aula.

CaCu3Ti4O12 (CCTO) is a complex oxide with a perovskite structure that is widely studied due to its dielectric and non-ohmic properties. The formation and composition of grains and grain boundaries are very important factors to improve these electrical properties. In this work, CCTO-based ceramics were processed by solid-state reaction at different calcination temperatures (700 °C to 1000 °C, for 4 h) and sintering at 1100 °C for 6 h aiming optimization in capacitor–varistor properties. The changes in crystal phase composition observed via XRD and chemical contrasts visualized by SEM/EDS point out that the disappearance of the secondary CuO phase of calcined powders is linked to complete Cu ion incorporation to the crystal structure of CCTO. This phenomenon culminated in sinterization via liquid phase formation, with abnormal grain growth for samples calcined at temperatures higher than 900 °C. The calcination occurring at 800 °C for 4 h, to produce CCTO with a more homogeneous microstructure, with apparent porosity of 2.67%, α of 5.49, EB of 1505 V cm−1, e′ (1 kHz) of 7506 and ΦB of 0.754 eV, was considered the best processing condition.

The TP53 tumor suppressor gene is the most frequently altered gene in tumors and an increasing number of studies highlight that mutant p53 proteins can acquire oncogenic properties, referred to as gain-of-function (GOF). Reactive oxygen species (ROS) play critical roles as intracellular messengers, regulating numerous signaling pathways linked to metabolism and cell growth. Tumor cells frequently display higher ROS levels compared to healthy cells as a result of their increased metabolism as well as serving as an oncogenic agent because of its damaging and mutational properties. Several studies reported that in contrast with the wild type protein, mutant p53 isoforms fail to exert antioxidant activities and rather increase intracellular ROS, driving a pro-tumorigenic survival. These pro-oxidant oncogenic abilities of GOF mutant p53 include signaling and metabolic rewiring, as well as the modulation of critical ROS-related transcription factors and antioxidant systems, which lead ROS unbalance linked to tumor progression. The studies summarized here highlight that GOF mutant p53 isoforms might constitute major targets for selective therapeutic intervention against several types of tumors and that ROS enhancement driven by mutant p53 might represent an “Achilles heel” of cancer cells, suggesting pro-oxidant drugs as a therapeutic approach for cancer patients bearing the mutant TP53 gene.

Immune checkpoint inhibitors are becoming standard treatments in several cancer types, profoundly changing the prognosis of a fraction of patients. Currently, many efforts are being made to predict responders and to understand how to overcome resistance in non-responders. Given the crucial role of myeloid cells as modulators of T effector cell function in tumors, it is essential to understand their impact on the clinical outcome of immune checkpoint blockade and on the mechanisms of immune evasion. In this review we focus on the existing clinical evidence of the relation between the presence of myeloid cell subsets and the response to anti-PD(L)1 and anti-CTLA-4 treatment. We highlight how circulating and tumor-infiltrating myeloid populations can be used as predictive biomarkers for immune checkpoint inhibitors in different human cancers, both at baseline and on treatment. Moreover, we propose to follow the dynamics of myeloid cells during immunotherapy as pharmacodynamic biomarkers. Finally, we provide an overview of the current strategies tested in the clinic that use myeloid cell targeting together with immune checkpoint blockade with the aim of uncovering the most promising approaches for effective combinations.

BackgroundMyeloid Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function.ResultsThe incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. ConclusionsWe demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge and provided a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.

In this work, inorganic pigments were synthesized by solid state reaction, from the incorporation of components of exhausted alkaline batteries. For this, after disassembling the batteries, the components were subjected to water leaching, milling and heat treatment at high temperatures with an addition of 33% (in mol) commercial or recovered from own alkaline batteries anodes zinc oxide. The obtained pigments were characterized by X-ray diffractometry, scanning electron microscopy, laser diffraction particle size, and UV-Vis diffuse reflectance spectroscopy. It was concluded that incorporation of the components of batteries generally yielded brown pigments with a structure of the spinel type ZnMn2O4. SEM and particle size distribution analyses show that the addition of ZnO leads to a reduction in average grain size of the powders. The pigments when applied to color ceramic enamels, polymers and paints show good performance in the coloring of these products, with potential for commercial application.

Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease characterized by the aberrations in multiple genes that drive pathogenesis and drug chemoresistance. In this study, we synthesize a library of seven novel nitric oxide-releasing gemcitabine pro-drugs (NO-GEMs) in order to improve the effectiveness of GEM by exploiting the therapeutic effects of NO. Among these NO-GEM pro-drugs we select 5b as the most effective compound in GEM-resistant PDAC cells. After its encapsulation in liposomes for drug delivery the intracellular NO level increases and nitration associated to activity inhibition of the multidrug resistance associated protein 5 (MRP5; ABCC5) occurs. This results in GEM intracellular accumulation and enhanced apoptotic cell death in GEM-resistant PDAC cells, which express MRP5 at higher levels than GEM-sensitive cells. Our results support the development of a new anti-tumoral strategy to efficiently affect GEM-resistant PDAC cells based on the usage of NO-GEM pro-drugs.

Risperidone is an antipsychotic drug commonly used in the treatment of schizophrenia and other psychiatric illnesses. Its main metabolite, 9-hydroxyrisperidone, also called paliperidone, exhibits pharmacological activity similar to risperidone, and the active fraction is the sum of the therapeutic concentrations of both. In this study, a novel method combining dispersive liquid-liquid microextraction and liquid chromatography coupled to mass spectrometry was developed to quantify the active fraction of these antipsychotic drugs in human plasma samples. The chromatographic analysis was performed employing an Ascentis® Express C18 chromatographic column (100 × 4.6 mm × 2.7 µm) and ammonium acetate (10 mmol/L): acetonitrile in gradient elution was employed as mobile phase. The flow rate was 0.5 mL/min, and the total run time was 8 min. The best microextraction conditions were chlorobenzene (80 µL) and acetone (500 µL) as extractor and dispersing solvent, respectively. The sample pH was adjusted to 12.0 and 10% NaCl was added in the samples in order to increase the ionic strength. The method was completely validated according to Guideline on Bioanalytical Method Validation. Finally, therapeutic drug monitoring capability of the new bioanalytical method was confirmed with the analysis of schizophrenic patient plasma.

INTRODUCTION: The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug. METHODS : High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1). RESULTS: Daily use of D-Amph 30 to 50 mg or L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each L-AmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died. CONCLUSIONS: By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Additional file 1. Supplementary materials and methods. Isolation of cell populations from peripheral blood and tissue of GBM patients, preparation of lipid nanocapsules, LNC incorporation studies, multiparametric flow cytometry, confocal microscopy, statistical analysis.

Objective Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction. Methods The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score ≥ 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via videoconference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention. Ethics and dissemination The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak., Highlights • No RCTs have tested mental health interventions in contagious disease outbreaks. • People with scleroderma face fear and isolation during COVID-19. • SPIN-CHAT is designed to improve mental health in SSc patients during COVID-19. • SPIN-CHAT provides 12 group sessions over 4 weeks. • The SPIN-CHAT trial will randomize 162 participants to intervention or waitlist.

A new method, simple and fast, for fluconazole (FLU) quantification in cerebrospinal fluid (CSF) samples using dispersive liquid-liquid microextraction (DLLME) and an eco-friendly mobile phase for HPLC-PDA was developed. The study of DLLME extraction condition covered the investigation of 12 combinations of extraction and disperser solvents followed by a fractional factorial design 2(7-3) to determine the influence of seven factors. After this stage, a central composite design was performed for three factors and a response surface was obtained. Aiming a compromise between a good recovery and a low organic solvent use it was established an extraction condition that consists of: 100 μL of chloroform, 100 μL of isopropyl alcohol, 200 μL of CSF, 200 μL of 50 mM phosphate buffer pH 7.3 and centrifugation for 5 min at 2200g and 4 °C. The HPLC analysis used an Ascentis® Express C18 column (100 mm × 4.6 mm, 2.7 μm) and an Ascentis® Express C18 guard column (3 mm × 4.6 mm, 2.7 μm), ethanol : water (15 : 85, v/v) as mobile phase, temperature of 45 °C, flow rate of 0.8 mL min-1 and phenacetin as internal standard. The method validation was performed according to European Agency's Guideline on Bioanalytical Validation Methodology and a linear range was obtained from 0.25 to 62.5 μg mL-1, with precision and accuracy within the recommended limits and recovery of 70% for FLU and 81% for phenacetin. Samples were stable in the studies performed and the method showed to be selective and with no carryover effect. The feasibility of the obtained method was confirmed by FLU determination at a CSF from a patient who was treated for neuromycosis. Therefore, here is described a method that meets many principles of green analytical chemistry and is useful for FLU therapeutic monitoring.

The productivity of the oilseed rape crop is responsive to the application of nitrogen (N) and the effect of N is sulfur (S)-dependent. In addition, storage may influence seed vigor. The aim of the present study was to assess the effect of fertilization with nitrogen and sulfur on the physiological quality of rapeseeds. All combinations of four doses of N (0, 40, 80, and 120 kg.ha-1) and five of S (0, 30, 60, 90, and 120 kg.ha-1) were evaluated with four replications each distributed in a randomized block design in a distroferric Red Latosol soil. The effects of the nutrients and their combinations on the physiological potential of rapeseeds were evaluated even immediately after harvest and 180 days of storage through the germination test, accelerated aging, field emergence and seedling performance. The application of N associated with S had a positive effect on the physiological quality of the seeds. The application of the 120 kg.ha-1 dose of N and the 80 kg.ha-1 dose of S promoted the highest germination and vigor of the seeds. Seed storage for a period of 180 days led to a drastic reduction in the physiological potential of the rapeseeds. Resumo: A produtividade da canola é responsiva à aplicação de N e o efeito de N depende de S. Além disso, o armazenamento pode influenciar o vigor das sementes. O objetivo do presente estudo foi avaliar o efeito da fertilização com nitrogênio e enxofre na qualidade fisiológica de sementes de canola. Todas as combinações de quatro doses de N (0, 40, 80 e 120 kg.ha-1) e cinco doses de S (0, 30, 60, 90 e 120 kg.ha-1) foram avaliadas com quatro repetições em delineamento de blocos casualizados, em um solo Latossolo Vermelho distroférrico. Os efeitos dos nutrientes e suas combinações sobre o potencial fisiológico das sementes de canola foram avaliados imediatamente após a colheita e após 180 dias de armazenamento pelo teste de germinação, envelhecimento acelerado, emergência em campo e desempenho de plântulas. A aplicação de N associada com S apresentou um efeito positivo na qualidade fisiológica de canola. A aplicação da dose de 120 kg.ha-1 de N, associada à dose de 80 kg.ha-1 de S, promoveu maior germinação e vigor das sementes de canola. O armazenamento das sementes por um período de 180 dias proporcionou uma redução acentuada no potencial fisiológico das sementes de canola.

We interact with the world around us by sensing a vast array of inputs and translating them into signals that can be interpreted by the brain. We have evolved many sensory receptors, each uniquely specialised to detect diverse stimuli. The hair cells are sensory receptors, initially developed to provide a sense of body position and movement, but later adapted to sense minute pressure waves in the environment that are perceived as sounds. As such, hair cells bestow a sense of hearing and balance, which are major advantages for survival. Mammals have four different types of hair cell, two of which are dedicated to hearing, the inner and outer hair cells, and the other two to balance, the type-I and type-II hair cells. While all hair cells employ common mechanisms to detect and relay signals from sound or motion, they also have unique attributes that specialise them for a specific functional role. In this chapter we describe the process of signal transmission in mammalian auditory and vestibular hair cells. Since mammalian hair cells do not regenerate, their loss results in permanent auditory or vestibular deficit. Efforts to regenerate or repair malfunctioning hair cells have recently intensified, mainly through gene, stem-cell and molecular therapy.

The recurring complaint that the initial training has not offered appropriate responses to the new demands of teachers' work in contemporary society incites the review of curricula that aims at these professionals’ development. In this context, the present study focuses on the critical analysis of an alternative curriculum organization developed in undergraduate courses at a Brazilian public university. The chosen guiding question was to investigate to what extent the proposal that has been implemented in such courses brings indicators to curriculum innovation in initial teacher development. The methodological approach adopted was the qualitative research. The data was obtained primarily through documental analysis. Data analysis comprised three steps: pre-analysis; exploitation of the material; data analysis and interpretation. The data indicates that the curriculum reform in progress manifests itself in changing movements in a set of core and relevant elements such as curriculum design and organization, teaching knowledge, models for teacher development, practical activities/training and teaching-learning methodology. Keywords: Initial teacher education; Curricular innovation; Undergraduate courses, La recurrente denuncia de que la formación inicial no está atendiendo las nuevas exigencias de trabajo de los profesores en la sociedad contemporánea plantea la cuestión sobre la revisión de los currículos que gradúan a dichos profesionales. En este contexto, el presente estudio se fija en el análisis crítico de una ordenación curricular alternativa que se desarrolla en cursos de licenciatura de una universidad pública brasileña. Se ha elegido como tema orientador investigar en qué medida la propuesta que se implementa en tales cursos vincula referentes para la innovación curricular en la formación inicial de profesores. Se toma como camino metodológico el abordaje cualitativo de investigación. Con el objetivo de colectar datos se privilegió un análisis documental. El análisis de datos estuvo compuesto por tres etapas: pre-análisis; estudio del material; tratamiento de los resultados obtenidos y interpretación. Los datos indican que la innovación curricular en marcha se manifiesta con el alzamiento a cambios en un conjunto de elementos centrales y relevantes, así como concepción y ordenación curricular, saberes docentes, modelos de formación, actividades funcionales/ práctica laboral y metodología enseñanza-aprendizaje. Palabras clave: Formación inicial de profesores; Innovación curricular; Licenciaturas, A recorrente denúncia de que a formação inicial não tem respondido às novas exigências do trabalho dos professores na sociedade contemporânea coloca em questão a revisão dos currículos que formam esses profissionais. Nesse contexto, o presente estudo tem como foco a análise crítica de uma organização curricular alternativa desenvolvida em cursos de licenciatura de uma universidade pública brasileira. Escolheu-se como questão orientadora investigar em que medida a proposta que vem sendo implementada nesses cursos traz referentes para inovação curricular na formação inicial de professores. Adota-se como caminho metodológico a abordagem qualitativa de pesquisa. Para obtenção dos dados privilegiou-se a análise documental. A análise dos dados compreendeu três etapas: pré-análise; exploração do material; tratamento dos resultados obtidos e interpretação. Os dados indicam que a inovação curricular em andamento se manifesta com movimentos de mudança em um conjunto de elementos centrais e relevantes, tais como concepção e organização curricular, saberes docentes, modelos de formação, atividades práticas/estágio e metodologia de ensino-aprendizagem. Palavras-chave: Formação inicial de professores; Inovação curricular; Licenciaturas

Made available in DSpace on 2022-04-29T08:45:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Casearin X (CAS X) is the major clerodane diterpene isolated from the leaves of Casearia sylvestris and has been extensively studied due to its powerful cytotoxic activity at low concentrations. Promising results for in vivo antitumor action have also been described when CAS X was administered intraperitoneally in mice. Conversely, loss of activity was observed when orally administered. Since the advancement of natural products as drug candidates requires satisfactory bioavailability for their pharmacological effect, this work aimed to characterize the CAS X metabolism by employing an in vitro microsomal model for the prediction of preclinical pharmacokinetic data. Rat and human liver microsomes were used to assess species differences. A high-performance liquid chromatography with diode-array detection (HPLC-DAD) method for the quantification of CAS X in microsomes was developed and validated according to European Medicines Agency guidelines. CAS X was demonstrated to be a substrate for carboxylesterases via hydrolysis reaction, with a Michaelis-Menten kinetic profile. The enzyme kinetic parameters were determined, and the intrinsic clearance was 1.7-fold higher in humans than in rats. The hepatic clearance was estimated by in vitro - in vivo extrapolation, resulting in more than 90% of the hepatic blood flow for both species. A qualitative study was also carried out for the metabolite identification by mass spectrometry and indicated the formation of the inactive metabolite CAS X dialdehyde. These findings demonstrate that CAS X is susceptible to first-pass metabolism and is a substrate for specific carboxylesterases expressed in liver, which may contribute to a reduction in antitumor activity when administered by the oral route. Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS) Departamento de Física e Química Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo, Avenida Bandeirantes 3900 Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Do Estado de São Paulo Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo