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Within and surrounding high-latitude cities, poor air quality disturbs Arctic ecosystems, influences the climate, and harms human health. The Fairbanks North Star Borough has wintertime particulate matter (PM) concentrations that exceed the Environmental Protection Agency's (EPA) threshold for public health. Particulate sulfate (SO4 2-) is the most abundant inorganic species and contributes approximately 20% of the total PM mass in Fairbanks, but air quality models underestimate observed sulfate concentrations. Here we quantify sulfate sources using size-resolved δ34S(SO4 2-), δ18O(SO4 2-), and Δ17O(SO4 2-) of particulate sulfate in Fairbanks from January 18th to February 25th, 2022 using a Bayesian isotope mixing model. Primary sulfate contributes 62 ± 12% of the total sulfate mass on average. Most primary sulfate is found in the size bin with a particle diameter < 0.7 µm, which contains 90 ±5% of total sulfate mass and poses the greatest risk to human health. Oxidation by all secondary formation pathways combined contributes 38 ± 12% of total sulfate mass on average, indicating that secondary sulfate formation is inefficient in this cold, dark environment. On average, the dominant secondary sulfate formation pathways are oxidation by H2O2 (13 ± 6%), O3 (8 ± 4%), and NO2 (8 ± 3%). These findings will inform mitigation strategies to improve air quality and public health in Fairbanks and possibly other high-latitude urban areas during winter.
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For the very first time, a microemulsion system in the Winsor II (WII) equilibrium was applied in a sample preparation method for extraction and pre-concentration in the determination of Pb, Cd, Co, Tl, Cu and Ni, in natural waters by high resolution continuum source atomic absorption spectrometry (HR-CS AAS). The method was optimized using the graphite furnace atomization. A simplex-centroid design for determine optimum extraction condition (77.5% aqueous phase, 5% of the oil phase, and 17.5% cosurfactant/surfactant ratio - C/S = 4) was applied. The optimized time for the sample preparations was around 30 min. The analytical performance of the optimized method using HR-CS GF AAS showed that the detection limits were: 0.09, 0.01, 0.06, and 0.05 µg L-1 for determination of Pb, Cd, Tl, and Co, respectively and the enrichment factors were between 6 and 19, considered excellent for all analytes. The RSD values were lower than 5%, demonstrating the good precision of the proposed method. When the optimized method was applied using the HR-CS F AAS, the sensibility increased 9 to 12 times for Cu and Ni, respectively. The analytical method was successfully applied for the determination of analytes in Certified Reference Material and real samples for natural waters such as Brackish water (recovery between 107 and 112%), Saline water (recovery between 83 and 94%), Produced water from oil industry (recovery between 98 and 110%) and Fresh water (recovery 80 and 87% to Cu and Ni respectively). All the results confirming the accuracy of the analytical method proposed. The repeatability of the measurements has been better 5% (n = 3), for all elements.
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Cadmio , Metales Pesados , Cadmio/análisis , Espectrofotometría Atómica/métodos , Plomo , Metales Pesados/análisisRESUMEN
In the development of electrochemical sensors, carbon micro-structured or micro-materials have been widely used as supports/modifiers to improve the performance of bare electrodes. In the case of carbon fibers (CFs), these carbonaceous materials have received extensive attention and their use has been proposed in a variety of fields. However, to the best of our knowledge, no attempts for electroanalytical determination of caffeine with CF microelectrode (µE) have been reported in the literature. Therefore, a homemade CF-µE was fabricated, characterized, and used to determine caffeine in soft beverage samples. From the electrochemical characterization of the CF-µE in K3Fe(CN)6 10 mmol L-1 plus KCl 100 mmol L-1, a radius of about 6 µm was estimated, registering a sigmoidal voltammetric profile that distinguishes a µE indicating that the mass-transport conditions were improved. Voltammetric analysis of the electrochemical response of caffeine at the CF-µE clearly showed that no effects were attained due to the mass transport in solution. Differential pulse voltammetric analysis using the CF-µE was able to determine the detection sensitivity, concentration range (0.3 to 4.5 µmol L-1), limit of detection (0.13 µmol L-1) and linear relationship (I (µA) = (11.6 ± 0.09) × 10-3 [caffeine, µmol L-1] - (0.37 ± 0.24) × 10-3), aiming at the quantification applicability in concentration quality-control for the beverages industry. When the homemade CF-µE was used to quantify the caffeine concentration in the soft beverage samples, the values obtained were satisfactory in comparison with the concentrations reported in the literature. Additionally, the concentrations were analytically determined by high-performance liquid chromatography (HPLC). These results show that these electrodes may be an alternative to the development of new and portable reliable analytical tools at low cost with high efficiency.
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O diabetes mellitus é uma doença endócrino-metabólica de grande prevalência mundial que pode culminar, quando descompensada, com diversas complicações, entre elas alterações neurológicas. Este relato de caso tem como objetivo descrever a presença de balismo e coreia em membros superiores bilateralmente propiciados pelo estado hiperglicêmico não cetótico em paciente com diabetes mellitus sem tratamento. Devido à agilidade em procurar por atendimento médico assim que se iniciaram os sintomas, e o correto manejo intra-hospitalar, nenhuma alteração foi visualizada em exame de imagem. No entanto, foram descartadas quaisquer outras causas que justificassem o quadro. Após o controle glicêmico adequado, houve melhora clínica progressiva e desaparecimento de movimentos involuntários.
Diabetes mellitus is an endocrine metabolic disease of great worldwide prevalence that can culminate, when decompensated, with several complications, including neurological changes. This case report aims to describe the presence of ballism and chorea in the upper limbs bilaterally caused by the non-ketotic hyperglycemic state in a patient with untreated diabetes mellitus. Due to the agility in seeking medical care as soon as the symptoms started, and the correct intra-hospital management, no changes were seen in the imaging scan. However, any other causes that justified the situation were ruled out. After adequate glycemic control, there was progressive clinical improvement and disappearance of involuntary movements.
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Humanos , Anciano , Anciano de 80 o más Años , Corea , Discinesias , Diabetes MellitusRESUMEN
CONTEXT: Metformin is an important oral anti-hyperglycemic used in diabetes. Polylactic-co-glycolic acid (PLGA) has been widely used due to its reliability in controlling the release of drugs. OBJECTIVE: This study evaluates the in vitro-in vivo availability of metformin hydrochloride-loaded polylactic-co-glycolic acid. MATERIAL AND METHODS: In vitro metformin release (Met-free or PLGA + Met-12.5 mg/mL per 360 min) was evaluated using static Franz vertical diffusion cells. The in vivo study was performed with two control groups (validation bioanalytical method) and two experimental groups of diabetic male Wistar rats treated with PLGA + Met 10 mg/kg or Met 100 mg/kg by oral gavage. Diabetes was induced by streptozotocin (40 mg/kg) through the penile vein. Blood samples were collected 0.5, 1, 4, 7, 10, 12, 18, 24, 36, 48 and 72 h and analysed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: PLGA + Met 10 mg/kg was released in the in vitro assay suggesting a parabolic diffusion kinetic model (K -0.0619-0.5h) with a 100% release profile in 10 h by controlled diffusion. The in vivo assay showed the apparent volume of distribution Vz/F (PLGA + Met 10 mg/kg, 40971.8 mL/kg vs. Met 100 mg/kg, 2174.58 mL/kg) and mean residence time MRTinf (PLGA + Met 10 mg/kg, 37.66 h vs. Met 100 mg/kg, 3.34 h). DISCUSSION AND CONCLUSIONS: The formulation modifies pharmacokinetics parameters such as apparent distribution volume and mean residence time. The PLGA + Met 10 mg/kg had a slower elimination rate compared to Met 100 mg/kg in diabetic rats in a periodontal disease experimental model.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Enfermedades Periodontales/tratamiento farmacológico , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/química , Liberación de Fármacos , Hipoglucemiantes/farmacocinética , Masculino , Metformina/farmacocinética , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas , Ratas Wistar , Estreptozocina , Espectrometría de Masas en Tándem , Distribución TisularRESUMEN
Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, is relatively suppressed in the more aggressively proliferative small cell lung cancer (SCLC). Here, we elucidate the role of the MAPK pathway and how it interacts with other signaling pathways in SCLC. We find that the most common SCLC subtype, SCLC-A associated with high expression of ASCL1, is selectively sensitive to MAPK activation in vitro and in vivo through induction of cell-cycle arrest and senescence. We show strong upregulation of ERK negative feedback regulators and STAT signaling upon MAPK activation in SCLC-A lines. These findings provide insight into the complexity of signaling networks in SCLC and suggest subtype-specific mitogenic vulnerabilities.
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The objective of this study was to evaluate the Calotropis procera fiber treated with NaOH combined with heat treatment as sorbent material for removal of petroleum and derivatives in cases of oil spill. The effects of oil viscosity, fiber/oil contact time, and the type of sorption system (oil and oil/water) were evaluated by experimental planning. The fiber obtained was characterized by Fourier transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (SEM-FEG), thermogravimetric analysis (TG/DTG), contact angle, and wettability. The fiber treated by combining NaOH and heat treatment (CPNaOHT) exhibited a large structure with an internal diameter of 42.99 ± 3.98 µm, roughness, and hydrophobicity on the surface with a contact angle of 101 ± 2°. The sorption capacity of oil ranged from 190.32 g/g to 98.9 g/g. After five cycles of recycling, the fiber still maintains about 70% of its initial sorption capacity and presented low liquid desorption (0.25 g). In this way, it can be used as an efficient sorbent to clean up spills of oil and oil products.
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Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor prognosis. Understanding the oncogenic drivers of SCLC may help define novel therapeutic targets. Recurrent genomic rearrangements have been identified in SCLC, most notably an in-frame gene fusion between RLF and MYCL found in up to 7% of the predominant ASCL1-expressing subtype. To explore the role of this fusion in oncogenesis and tumor progression, we used CRISPR/Cas9 somatic editing to generate a Rlf-Mycl-driven mouse model of SCLC. RLF-MYCL fusion accelerated transformation and proliferation of murine SCLC and increased metastatic dissemination and the diversity of metastatic sites. Tumors from the RLF-MYCL genetically engineered mouse model displayed gene expression similarities with human RLF-MYCL SCLC. Together, our studies support RLF-MYCL as the first demonstrated fusion oncogenic driver in SCLC and provide a new preclinical mouse model for the study of this subtype of SCLC. SIGNIFICANCE: The biological and therapeutic implications of gene fusions in SCLC, an aggressive metastatic lung cancer, are unknown. Our study investigates the functional significance of the in-frame RLF-MYCL gene fusion by developing a Rlf-Mycl-driven genetically engineered mouse model and defining the impact on tumor growth and metastasis. This article is highlighted in the In This Issue feature, p. 2945.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Fusión Génica , Genes myc , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Proteínas Proto-Oncogénicas c-myc , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Proteínas de Unión a TelómerosRESUMEN
Patient-derived xenografts are high fidelity in vivo tumor models that accurately reflect many key aspects of human cancer. In contrast to either cancer cell lines or genetically engineered mouse models, the utility of PDXs has been limited by the inability to perform targeted genome editing of these tumors. To address this limitation, we have developed methods for CRISPR-Cas9 editing of PDXs using a tightly regulated, inducible Cas9 vector that does not require in vitro culture for selection of transduced cells. We demonstrate the utility of this platform in PDXs (1) to analyze genetic dependencies by targeted gene disruption and (2) to analyze mechanisms of acquired drug resistance by site-specific gene editing using templated homology-directed repair. This flexible system has broad application to other explant models and substantially augments the utility of PDXs as genetically programmable models of human cancer.
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Sistemas CRISPR-Cas , Edición Génica , Animales , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Genómica , Xenoinjertos , Humanos , RatonesRESUMEN
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.
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Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , ADN Helicasas/genética , Diseño de Fármacos , Mutación , Proteínas Nucleares/genética , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Administración Oral , Animales , Antineoplásicos/química , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Modelos Moleculares , Conformación Proteica , Relación Estructura-Actividad , Factores de Transcripción/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Electrochemical advanced oxidation processes such as electrooxidation (EO), electrooxidation with hydrogen peroxide generation (EO-H2O2) and electro-Fenton process (EF) have been investigated as alternative treatment techniques for complete removal of anionic surfactants and organic matters from real carwash wastewater. The electrochemical processes were performed with acidified real carwash wastewater using boron doped anode and carbon felt cathode. In all cases, the chemical oxygen demand (COD) removal efficiency was always increased with rise in applied current and complete organic matter decay was achieved at applied current of 500â¯mA or above after 6â¯h of electrolysis. Faster and higher COD decay was observed with EF compared to either EO or EO-H2O2 treatment, at all currents and electrolysis time. Besides, complete degradation of anionic surfactants - the major organic content of the wastewater could be achieved at all applied currents studied irrespective of the process used, indicating the efficacy of processes for total remediation of real carwash wastewater. The short-chain carboxylic acids formed as the final organic byproducts were identified and quantified by ion-exclusion chromatography. More so, lower energy consumption and higher current efficiency were achieved with EF compared to EO-H2O2. Electrochemical treatment was found to be a powerful technology for the complete abatement of organic matter in carwash wastewater for possible reuse.
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Técnicas Electroquímicas/métodos , Aguas Residuales/química , Contaminantes Químicos del Agua/químicaRESUMEN
Water scarcity is one of the major concerns worldwide. In order to secure this appreciated natural resource, management and development of water treatment technologies are mandatory. One feasible alternative is the consideration of water recycling/reuse at the household scale. Here, the treatment of actual washing machine effluent by electrochemical advanced oxidation processes was considered. Electrochemical oxidation and electro-Fenton technologies can be applied as decentralized small-scale water treatment devices. Therefore, efficient decolorization and total organic abatement have been followed. The results demonstrate the promising performance of solar photoelectro-Fenton process, where complete color and organic removal was attained after 240 min of treatment under optimum conditions by applying a current density of 66.6 mA cm-2. Thus, electrochemical technologies emerge as promising water-sustainable approaches.
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Técnicas Electroquímicas/métodos , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Técnicas Electroquímicas/instrumentación , Electrodos , Peróxido de Hidrógeno/química , Hierro/química , Oxidación-Reducción , Luz Solar , Purificación del Agua/instrumentaciónRESUMEN
Introdução: Pierre Robin, em 1923, descreveu a sequência das malformações e as correlacionou com os sinais clínicos de insuficiência respiratória, o que trouxe a constatação da necessidade de tratamento, muitas vezes urgente. A conduta terapêutica deve ser individualizada para cada caso e respeitar o quadro apresentado pelo paciente. Objetivo: O presente estudo consiste em uma revisão sobre a Sequência de Pierre Robin e sua abordagem terapêutica, através de distração osteogênica da mandíbula, com a finalidade de demonstrar a efetividade do procedimento. Método: Estudo descritivo de abordagem qualitativa tipo relato de caso. Resultados e conclusão: A aplicação da técnica possibilitou a correção das anormalidades craniofaciais, o que minimizou os prejuízos causados pela síndrome (AU)
Introduction: In 1923, Pierre Robin described and sequenced the malformations and correlated them with the clinical signs of respiratory failure, which eventually confirmed the need for treatment, often urgent. The therapeutic approach should be individualized for each case and must respect the patient's clinical picture. Aim: The present study consists of a review on the Pierre Robin sequence and its therapeutic approach through osteogenic distraction of the mandible in order to demonstrate the effectiveness of the procedure. Method: A descriptive study with a qualitative approach, case report type. Results and conclusion: The application of the technique made possible the correction of craniofacial abnormalities, which minimized the damage caused by the syndrome (AU)