Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma.

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), is the primary cause of brain tumor-related death in pediatric patients. DIPG is characterized by a median survival of <12 months from diagnosis, harboring the worst 5-year survival rate of any cancer. Corticosteroids and radiation are the mainstay of therapy; however, they only provide transient relief from the devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but the majority have been unsuccessful in demonstrating a survival benefit beyond radiation alone. Although many barriers hinder brain drug delivery in DIPG, one of the most significant challenges is the blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across the BBB. In brain cancer, the BBB is referred to as the blood-brain tumor barrier (BBTB), where tumors disrupt the structure and function of the BBB, which may provide opportunities for drug delivery. However, the biological characteristics of the brainstem's BBB/BBTB, both under normal physiological conditions and in response to DIPG, are poorly understood, which further complicates treatment. Better characterization of the changes that occur in the BBB/BBTB of DIPG patients is essential, as this informs future treatment strategies. Many novel drug delivery technologies have been investigated to bypass or disrupt the BBB/BBTB, including convection enhanced delivery, focused ultrasound, nanoparticle-mediated delivery, and intranasal delivery, all of which are yet to be clinically established for the treatment of DIPG. Herein, we review what is known about the BBB/BBTB and discuss the current status, limitations, and advances of conventional and novel treatments to improving brain drug delivery in DIPG.

In Situ Formation of Nano Ni-Co Oxyhydroxide Enables Water Oxidation Electrocatalysts Durable at High Current Densities.

The oxygen evolution reaction (OER) limits the energy efficiency of electrocatalytic systems due to the high overpotential symptomatic of poor reaction kinetics; this problem worsens over time if the performance of the OER electrocatalyst diminishes during operation. Here, a novel synthesis of nanocrystalline Ni-Co-Se using ball milling at cryogenic temperature is reported. It is discovered that, by anodizing the Ni-Co-Se structure during OER, Se ions leach out of the original structure, allowing water molecules to hydrate Ni and Co defective sites, and the nanoparticles to evolve into an active Ni-Co oxyhydroxide. This transformation is observed using operando X-ray absorption spectroscopy, with the findings confirmed using density functional theory calculations. The resulting electrocatalyst exhibits an overpotential of 279 mV at 0.5 A cm-2 and 329 mV at 1 A cm-2 and sustained performance for 500 h. This is achieved using low mass loadings (0.36 mg cm-2 ) of cobalt. Incorporating the electrocatalyst in an anion exchange membrane water electrolyzer yields a current density of 1 A cm-2 at 1.75 V for 95 h without decay in performance. When the electrocatalyst is integrated into a CO2 -to-ethylene electrolyzer, a record-setting full cell voltage of 3 V at current density 1 A cm-2 is achieved.

Medições morfométricas aplicadas na avaliação do peso corporal de pirarucus (Arapaima gigas) / Morphometric measurements applied in the body weight evaluation of pirarucu (Arapaima gigas) / Mediciones morfométricas aplicadas en la evaluación del peso corporal de arapaimas (Arapaima gigas)

Estudos morfométricos são amplamente utilizados em espécies terrestres de grande porte. O pirarucu é uma espécie de peixe carnívoro de rápido crescimento alcançando 10 kg durante seu primeiro ano de vida em ambiente de cultivo. Objetivou-se avaliar correlações entre peso e medidas corporais de pirarucus visando elaborar equações para estimar o peso desses, por meio da coleta de medidas morfométricas. Como também comparar a concentração de glicose sanguínea de acordo com o peso. Foram avaliados 16 exemplares com pesos médios variando entre 23,58 e 52,87kg. De cada animal foram obtidos o peso (kg), comprimento total (cm), comprimento padrão (cm), comprimento da cabeça (cm), diâmetro ao final da cabeça (cm), diâmetro mediano (cm), diâmetro anterior nadadeira anal (cm), altura (cm), largura (cm) e glicose sanguínea (dm/L). Foi observada correlação positiva entre todas as variáveis. A mais alta correlação foi obtida ao relacionar o peso e o comprimento total, no entanto, dentre as correlações mais fortes, foram selecionadas o peso x diâmetro médio (r = 0,9669, p< 0,01) e peso x diâmetro anterior a nadadeira anal (r = 0,9671, p< 0,01) para ser submetidas à análise de regressão polinomial devido a maior facilidade de mensuração durante a contenção do animal, levando em consideração o seu porte elevado. Deste modo, conclui-se que foi possível estimar o peso por meio de equações de regressão utilizando o diâmetro mediano (y=0,577x + 57,669, r2 = 0,93) e diâmetro anterior à nadadeira anal (y=0,7253x + 42,518, r2 = 0,93). A glicose sanguínea diminuiu com o aumento do peso dos pirarucus.(AU)

Morphometric studies are widely used in large terrestrial species. Pirarucu is a fast-growing carnivorous fish species reaching 10 kg during its first year of life in a farming environment. The purpose of this study was to evaluate correlations between weight and body measures of pirarucu to develop equations to estimate their weight through the collection of morphometric measures, as well as comparing blood glucose concentration according to weight. A total of 16 specimens with average weights ranging from 23.58 to 52.87 kg were evaluated. Weight (kg), total length (cm), standard length (cm), head length (cm), diameter at the end of the head (cm), median diameter (cm), diameter before anal fin (cm), height (cm), width (cm), and blood glucose (dm/L) were measured from each specimen. A positive correlation was observed among all variables. The highest correlation was obtained by relating weight and total length; however, among the strongest correlations, weight x average diameter (r = 0.9669, p <0.01), and weight x diameter before anal fin (r = 0.9671, p <0.01) were subjected to polynomial regression analysis due to being of easier measurement during animal containment, taking into account its size. Thus, it can be conclude that it is possible to estimate weight using regression equations using the median diameter (y = 0.577x + 57.669, r2 = 0.93) and diameter before the anal fin (y = 0.7253x + 42.518, r2 = 0.93). It could also be noted that blood glucose decreased with increasing weight of pirarucu.(AU)

Estudios morfométricos son ampliamente utilizados en especies terrestres de gran porte. El arapaima es una especie de pez carnívoro de rápido crecimiento que alcanza los 10 kg durante su primer año de vida en un ambiente de cultivo. El objetivo fue evaluar correlaciones entre el peso y las medidas corporales de arapaimas buscando elaborar ecuaciones para estimar su peso, mediante la recolección de medidas morfométricas. Además de comparar la concentración de glucosa sanguínea según el peso. Se evaluaron 16 ejemplares con pesos promedio que oscilaron entre 23,58 y 52,87 kg. De cada animal se obtuvo el peso (kg), longitud total (cm), longitud estándar (cm), longitud de la cabeza (cm), diámetro al final de la cabeza (cm), diámetro mediano (cm), diámetro de la aleta anal anterior (cm), altura (cm), ancho (cm) y glucosa sanguínea (dm/L). Se observó una correlación positiva entre todas las variables. La correlación más alta se obtuvo al relacionar el peso y la longitud total, sin embargo, entre las correlaciones más fuertes, se seleccionó el peso x diámetro promedio (r = 0.9669, p<0.01) y peso x diámetro antes de la aleta anal (r = 0.9671, p<0.01) para ser sometido a análisis de regresión polinomial debido a la facilidad de medición durante la contención del animal, teniendo en cuenta su gran tamaño. Así, se concluye que fue posible estimar el peso por medio de ecuaciones de regresión utilizando el diámetro mediano (y = 0.577x + 57.669, r2 = 0.93) y el diámetro antes de la aleta anal (y = 0.7253x + 42.518, r2 = 93). La glucosa sanguínea redujo con el aumento de peso de los arapaimas.(AU)

Subcellular distribution of human tyrosine hydroxylase isoforms 1 and 4 in SH-SY5Y cells.

Tyrosine hydroxylase (TH) is the key enzyme that controls the rate of synthesis of the catecholamines. SH-SY5Y cells with stable transfections of either human tyrosine hydroxylase isoform 1 (hTH1) or human tyrosine hydroxylase isoform 4 (hTH4) were used to determined the subcellular distribution of TH protein and phosphorylated TH, under basal conditions and after muscarine stimulation. Muscarine was previously shown to increase the phosphorylation of only serine 19 and serine 40 in hTH1 cells. Under basal conditions, the hTH1 and hTH4 proteins, their serine 19 phosphorylated forms and hTH1 phosphorylated at serine 40 were all similarly distributed; with ~80% in the cytosolic fraction, ~20% in the membrane fraction, and less than 1%, or not detectable, in the nuclear fraction. However, hTH4 phosphorylated at serine 71 had a significantly different distribution with ~65% cytosolic and ~35% membrane associated. Muscarine stimulation led to hTH1 being redistributed from the cytosol and nuclear fractions to the membrane fraction and hTH4 being redistributed from the cytosol to the nuclear fraction. These muscarine stimulated redistributions were not due to TH phosphorylation at serine 19, serine 40, or serine 71 and were most likely due to TH binding to proteins whose phosphorylation was increased by muscarine. This is the first study to show a difference in subcellular distribution between two human TH isoforms under basal and stimulated conditions.

A Rodent Model of Anxiety: The Effect of Perinatal Immune Challenges on Gastrointestinal Inflammation and Integrity.

OBJECTIVES: Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations may be contributing to heightened immune signals that have the potential to disrupt neuronal homeostasis and exacerbate behavioural deficits. The current study aimed to determine whether the well-characterized animal model of neuropsychopathology, the maternal immune activation (MIA) model, produced GI inflammation and integrity disruptions in association with anxiety-like behaviour. METHODS: Pregnant Wistar rats were exposed to the viral mimetic polyriboinosinic:polyribocytidilic acid (polyI:C) on gestational days (GD) 10 and 19. Evidence of ANS activation, GI inflammation, and GI barrier integrity was assessed in both neonatal (postnatal day, P7) and adult (P84) offspring. Anxiety-like behaviour was assessed at P100. RESULTS: Neonatal MIA offspring exhibited an altered intestinal inflammatory profile and evidence of an increase in lymphoid aggregates. MIA neonates also displayed disruptions to GI barrier tight junction protein mRNA. In addition, adult MIA offspring exhibited an increase in anxiety-like behaviours. CONCLUSION: These results indicate that the MIA rat model, which is well documented to produce behavioural, neurochemical, and neuroanatomical abnormalities, also produces GI inflammation and integrity disruptions. We suggest that this model may be a useful tool to elucidate biological pathways associated with neuropsychiatric disorders.

Simultaneous nitrification and denitrification in the activated sludge systems of continuous flow.

This study has investigated the biological nitrogen removal by simultaneous nitrification and denitrification (SND) processes in a system of continuous flow activated sludge (AS) process. The investigation had four stages and evaluated the system behavior under different solid retention times (SRT), food-to-mass (F/M) ratios and dissolved oxygen (DO) concentrations. The data showed that the concentration of DO 0.5±0.2 mgO2/L did not affect the growth of heterotrophic bacteria (2.2-3.1 d-1 at 20°C) and autotrophic nitrifying bacteria (0.16-1.94 d-1 at 20°C), resulting in values very close to those obtained in conventional AS processes. The chemical oxygen demand (COD) removal was over 90% in all stages. The decrease in SRT from 37.2 to 27.8, 19.0 and 10.0 days had no significant influence on the development of SND. In the stage where the carbon/nitrogen (C/N) ratio was 4.3 mgCOD/mgN  L, SND efficiency was of 55%. In the following stages, the C/N ratio was increased and it was possible to achieve efficiencies higher than 98% SND. Overall, the data showed that appropriate controls of carbon and nitrogen input are required to achieve an efficient SND. An established SND technology can save operation time and energy, and might replace the traditional two stages: biological nitrification and denitrification process.

Desempenho de reator integrado de lodo ativado com biofilme em leito movel / Integrated fixed film activated sludge reactor performance

O objetivo deste estudo foi avaliar os efeitos da presença de suportes plásticos móveis (carriers) no processo de lodo ativado por meio da operação, sob diferentes tempos de retenção de sólidos para remoção de matéria carbonácea e nitrogênio, de dois sistemas aeróbios. Um deles, denominado LAC, foi constituído por reatores de lodo ativado com biomassa apenas em suspensão, e comparado com outro, LAI, com reatores integrados de lodo ativado com biofilme em leito móvel. Monitorou-se o crescimento das biomassas em suspensão e aderida e as condições ambientais nos reatores. Testes respirométricos determinaram os coeficientes cinéticos relativos à nitrificação. Foi possível a aplicação de carga de aproximadamente duas vezes a que foi suportada por um sistema de lodo ativado, a nitrificação se estendeu até reduzidas idades do lodo aeróbio e a desnitrificação ocorreu eficientemente. As velocidades específicas de crescimento das bactérias nitritantes e nitratantes foram determinadas para o processo com biofilme aderido, resultando similares às obtidas apenas com biomassa em suspensão.

The aim of this study was to evaluate the effects of plastic media carriers presence in the activated sludge process through the operation under different solids retention times, for the removal of carbonaceous organic matter and ammonia nitrogen, of two aerobic systems. One of them, called LAC, was constituted by activated sludge reactors with suspended biomass only and compared with another, LAI, with integrated fixed-film activated sludge reactors. The growth of attached and suspended biomass and environmental conditions in the reactors have been monitored. Respirometric analyzes were used to determine kinetic coefficients related to nitrification. It was possible to apply approximately twice the load supported by an activated sludge system, nitrification was extended until low solids retention times related to the aerobic and suspended biomass, and denitrification has occurred efficiently. The specific growth rate of nitrifying bacteria in attached biomass has resulted similar to that observed in suspended biomass.

Characteristics of WWTP sludge after drying in greenhouse for agricultural purposes.

The sludge generated by sewage treatment which meets regulatory standards can be used in agriculture. With this understanding, the focus of this study is the evaluation of the agricultural characteristics and inorganic substances in excess activated sludge, which was subjected to drying in a greenhouse. The variables (factor) evaluated during the drying process were: type of sludge (digested or not digested), addition of lime to the sludge, and the physical layout and rotation of sludge in the greenhouse. The parameters monitored for this assessment were moisture, volatile solids and pH. The greenhouse cover and sides were made of translucent plastic to allow the penetration of solar radiation and prevent water from entering. A impermeable floor was used. The sludge was generated in sewage treatment plants located in the metropolitan region of Grande Vitória, Espírito Santo, Brazil. The solar drying of wastewater sludge in a greenhouse presented satisfactory results.

Aplicação de processos físico-químicos como alternativa de pré e pós-tratamento de lixiviados de aterros sanitários / Physical-chemical processes as an alternative to pre-and post-treatment of landfill leachate

O presente artigo objetivou avaliar a aplicação da operação de stripping como pré-tratamento de um lixiviado de aterro sanitário visando à redução da carga de amônia afluente a um sistema biológico de tratamento, bem como, a utilização do processo de coagulação-floculação-sedimentação para a remoção da matéria orgânica recalcitrante de um lixiviado de aterro pré-tratado em um sistema de lodo ativado. As taxas de remoção de nitrogênio amoniacal variaram entre 3,5 e 3,6 mg N-NH3.L-1.h-1 para o sistema de stripping composto por um reator submetido à agitação mecânica e entre 3,2 e 3,3 mg N-NH3.L-1.h-1 para o reator submetido à aeração com bolhas grossas. Quanto ao pós-tratamento, os resultados obtidos indicaram que são requeridas dosagens acima de 400 mg Fe+3.L-1 e 400 mg Al+3.L-1, para a obtenção de eficiências de remoção de matéria orgânica recalcitrante superiores a 90 por cento.

The aim of this article was evaluate the implementation of the ammonia stripping as a pretreatment for landfill leachate and the use of the coagulation-flocculation-sedimentation process for the removal of refractory organic compounds present in a landfill leachate pretreated in an activated sludge system. The rates of ammonia nitrogen removal ranged between 3.5 and 3.6 mg NH3-N.L-1.h-1in a lab scale reactor (working volume of 20 L) equipped with a mechanical stirrer and 3.2 and 3.3 mg NH3-N.L-1.h-1in a lab scale aerated column (working volume of 10 L). It was possible to achieve removals above 90 percent of refractory organic compounds (measured as apparent color) applied coagulant dosage about 400 mg Fe+3.L-1 and 400 mg Al+3.L-1.

Epidemiological aspects of an infection by Brucella abortus in risk occupational groups in the microregion of Araguaína, Tocantins.

The aim of this paper was to study some epidemiological aspects of the infection by Brucella abortus in risk occupational groups in the microregion of Araguaína, Tocantins. For antibody research, 645 serum samples were analyzed by the complement fixation test (CF). A 4.0% frequency was found (26/645) in patients' serum and among those 4.1% (23/551) were slaughterhouses employees and 8.1% (3/37) rural workers. Of the total positive samples, three (2.0%) were women and 23 (4.7%) men; ten (2.9%) were between the ages of 18 and 30, six (3.4%) between 31 and 40, and nine (8.0%) were above 41 years of age. Risk factors for brucellosis in the study groups were age, background (OR = 2.45; CI 95% = 0.98 to 6.10) and previous work conducted with production animals (OR 2.36; CI 95% = 0.95 to 6.02). It was concluded that the infection by Brucella abortus is found in some risk occupational groups in the microregion of Araguaína, Tocantins, and control and prophylactic measures must be implemented emphasizing risk factors identified in the study.

Epidemiological aspects of an infection by Brucella abortus in risk occupational groups in the microregion of Araguaína, Tocantins

The aim of this paper was to study some epidemiological aspects of the infection by Brucella abortus in risk occupational groups in the microregion of Araguaína, Tocantins. For antibody research, 645 serum samples were analyzed by the complement fixation test (CF). A 4.0 percent frequency was found (26/645) in patients' serum and among those 4.1 percent (23/551) were slaughterhouses employees and 8.1 percent (3/37) rural workers. Of the total positive samples, three (2.0 percent) were women and 23 (4.7 percent) men; ten (2.9 percent) were between the ages of 18 and 30, six (3.4 percent) between 31 and 40, and nine (8.0 percent) were above 41 years of age. Risk factors for brucellosis in the study groups were age, background (OR = 2.45; CI 95 percent = 0.98 to 6.10) and previous work conducted with production animals (OR 2.36; CI 95 percent = 0.95 to 6.02). It was concluded that the infection by Brucella abortus is found in some risk occupational groups in the microregion of Araguaína, Tocantins, and control and prophylactic measures must be implemented emphasizing risk factors identified in the study.

Comportamiento de una laguna de pulido en la región metropolitana de Curitiba, Brasil y estudio de utilización de lentejas de aguas para mejorar la calidad del efluente. Parte 1

Se evalua una laguna de pulido encargada del postratamiento del efluente cloacal proveniente de un reactor UASB, en la región metropolitana de Curitiba, Brsil. La laguna fue estudiada en operación a escala real y tambien, con sombreado parcial en la parte final de la misma, obtenida mediante lentejas de agua. El objetivo principal fue evaluar si el uso de lentejas de agua mejora la calidad del efluente, ya que los vegetales a través del sombreado, impediran el paso de la luz y con ello el crecimiento de las algas. La segunda parte del artículo continua en el No. 94

Comportamiento de una laguna de pulido en la región metropolitana de Curitiba, Brasil y estudio de utilización de lentejas de aguas para mejorar la calidad del efluente. Parte 1

Se evalua una laguna de pulido encargada del postratamiento del efluente cloacal proveniente de un reactor UASB, en la región metropolitana de Curitiba, Brsil. La laguna fue estudiada en operación a escala real y tambien, con sombreado parcial en la parte final de la misma, obtenida mediante lentejas de agua. El objetivo principal fue evaluar si el uso de lentejas de agua mejora la calidad del efluente, ya que los vegetales a través del sombreado, impediran el paso de la luz y con ello el crecimiento de las algas. La segunda parte del artículo continua en el No. 94

Remoción de nutrientes en sistemas de lodos activados pretratados en reactores UASB

Se evalúa la remoción biológica de nitrógeno presenta en el efluente de un reactor anaerobio tipo UASB, a través de un sistema de lodos activados, utilizando como fuente de energía el carbono orgánico de este efluente. Tambien se evalua la remoción fisico-química de fósforo presente en el efluente del reactor anaerobio tipo UASB, a través de la edición de dósis variables de cloruro férrico en un reactor anaerobio del sistema de lodos activados, asi como el desempeño del sistema de lodos activados en la remoción de la materia orgánica remanente en el reactor anaeróbio UASB

Remoción de nutrientes en sistemas de lodos activados pretratados en reactores UASB

Se evalúa la remoción biológica de nitrógeno presenta en el efluente de un reactor anaerobio tipo UASB, a través de un sistema de lodos activados, utilizando como fuente de energía el carbono orgánico de este efluente. Tambien se evalua la remoción fisico-química de fósforo presente en el efluente del reactor anaerobio tipo UASB, a través de la edición de dósis variables de cloruro férrico en un reactor anaerobio del sistema de lodos activados, asi como el desempeño del sistema de lodos activados en la remoción de la materia orgánica remanente en el reactor anaeróbio UASB

Lagoas aeradas tratando esgotos sanitários: reduçäo no custo de energia elétrica / Aerated lagoons treatening domestic wastewater: influence on energy costs reduce

Verifica a possibilidade de operaçäo eficiente e estável de um sistema constituído de lagoa aerada aeróbia seguida de lagoa de decantaçäo, com uma interrupçäo programada de três horas por dia no sistema de aeraçäo. Estuda o efeito sobre a economia da operaçäo do sistema, tendo como referência o sistema tarifário vigente que prevê tarifas mais elevadas durante o período de ponta de consumo de energia elétrica

Filtros biológicos de alta taxa - Lagoas aeradas - Aspectos teóricos resultados experimentais - Consideracoes sobre o projeto

Considerando el enunciado del trabajo el autor presenta detalladamente todo lo relacionado con lagunas aereadas para el tratamiento de aguas residuales

Estudos sobre oxidaçäo de sulfetos em reservatórios

Foram desenvolvidos ensaios de campo visando estudar a oxidaçäo de sulfetos no reservatório de Pirapora, na Bacia do Alto Tietê. Durante o período de estiagem de 1984 os níveis de sulfeto no reservatório eram sempre superiores a 10mg/1, chegando a atingir 24mg/1. Para oxidaçäo dos sulfetos foram utilizados oxigênio do ar e oxigênio puro, em testes distintos, observando-se que era possível a remoçäo de sulfetos em cerca de 85% com um tempo de reaçäo entre 90 e 120 minutos. A liberaçäo de sulfeto para a atmosfera foi inferior a 1% do sulfeto removido, o que em muitos casos pode causar sérios incovenientes. A oxidaçäo de sulfetos, tanto com ar como com oxigênio puro se deu em três etapas, todas elas obedecendo a cinética de primeira ordem, tendo sido as suas constantes determinadas. O trabalho descreve os ensaios desenvolvidos, apresenta e discute os resultados obtidos, bem como as conclusöes a que se chegaram