PAH bioremediation with Rhodococcus rhodochrous ATCC 21198: Impact of cell immobilization and surfactant use on PAH treatment and post-remediation toxicity.

Polycyclic aromatic hydrocarbons (PAHs) are prevalent environmental contaminants that are harmful to ecological and human health. Bioremediation is a promising technique for remediating PAHs in the environment, however bioremediation often results in the accumulation of toxic PAH metabolites. The objectives of this research were to demonstrate the cometabolic treatment of a mixture of PAHs by a pure bacterial culture, Rhodococcus rhodochrous ATCC 21198, and investigate PAH metabolites and toxicity. Additionally, the surfactant Tween ® 80 and cell immobilization techniques were used to enhance bioremediation. Total PAH removal ranged from 70-95% for fluorene, 44-89% for phenanthrene, 86-97% for anthracene, and 6.5-78% for pyrene. Maximum removal was achieved with immobilized cells in the presence of Tween ® 80. Investigation of PAH metabolites produced by 21198 revealed a complex mixture of hydroxylated compounds, quinones, and ring-fission products. Toxicity appeared to increase after bioremediation, manifesting as mortality and developmental effects in embryonic zebrafish. 21198's ability to rapidly transform PAHs of a variety of molecular structures and sizes suggests that 21198 can be a valuable microorganism for catalyzing PAH remediation. However, implementing further treatment processes to address toxic PAH metabolites should be pursued to help lower post-remediation toxicity in future studies.

Where the rubber meets the road: Emerging environmental impacts of tire wear particles and their chemical cocktails.

About 3 billion new tires are produced each year and about 800 million tires become waste annually. Global dependence upon tires produced from natural rubber and petroleum-based compounds represents a persistent and complex environmental problem with only partial and often-times, ineffective solutions. Tire emissions may be in the form of whole tires, tire particles, and chemical compounds, each of which is transported through various atmospheric, terrestrial, and aquatic routes in the natural and built environments. Production and use of tires generates multiple heavy metals, plastics, PAH's, and other compounds that can be toxic alone or as chemical cocktails. Used tires require storage space, are energy intensive to recycle, and generally have few post-wear uses that are not also potential sources of pollutants (e.g., crumb rubber, pavements, burning). Tire particles emitted during use are a major component of microplastics in urban runoff and a source of unique and highly potent toxic substances. Thus, tires represent a ubiquitous and complex pollutant that requires a comprehensive examination to develop effective management and remediation. We approach the issue of tire pollution holistically by examining the life cycle of tires across production, emissions, recycling, and disposal. In this paper, we synthesize recent research and data about the environmental and human health risks associated with the production, use, and disposal of tires and discuss gaps in our knowledge about fate and transport, as well as the toxicology of tire particles and chemical leachates. We examine potential management and remediation approaches for addressing exposure risks across the life cycle of tires. We consider tires as pollutants across three levels: tires in their whole state, as particulates, and as a mixture of chemical cocktails. Finally, we discuss information gaps in our understanding of tires as a pollutant and outline key questions to improve our knowledge and ability to manage and remediate tire pollution.

Time course of western diet (WD) induced nonalcoholic steatohepatitis (NASH) in female and male Ldlr-/- mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identification of factors contributing to the onset and progression of NAFLD have the potential to direct novel strategies to combat NAFLD. METHODS: We examined the time course of western diet (WD)-induced NAFLD and its progression to nonalcoholic steatohepatitis (NASH) in age-matched female and male Ldlr-/- mice, with time-points at 1, 4, 8, 20 and 40 weeks on the WD. Controls included Ldlr-/- mice maintained on a purified low-fat diet (LFD) for 1 and 40 weeks. The approach included quantitation of anthropometric, plasma and liver markers of disease, plus hepatic histology, lipids, oxylipins, gene expression and selected metabolites. RESULTS: One week of feeding the WD caused a significant reduction in hepatic essential fatty acids (EFAs: 18:2, ω6, 18:3, ω3) which preceded the decline in many C20-22 ω3 and ω6 polyunsaturated fatty acids (PUFA) and PUFA-derived oxylipins after 4 weeks on the WD. In addition, expression of hepatic inflammation markers (CD40, CD44, Mcp1, Nlrp3, TLR2, TLR4, Trem2) increased significantly in both female & male mice after one week on the WD. These markers continued to increase over the 40-week WD feeding study. WD effects on hepatic EFA and inflammation preceded all significant WD-induced changes in body weight, insulin resistance (HOMA-IR), oxidative stress status (GSH/GSSG ratio) and histological and gene expression markers of macrosteatosis, extracellular matrix remodeling and fibrosis. CONCLUSIONS: Our findings establish that feeding Ldlr-/- mice the WD rapidly lowered hepatic EFAs and induced key inflammatory markers linked to NASH. Since EFAs have an established role in inflammation and hepatic inflammation plays a major role in NASH, we suggest that early clinical assessment of EFA status and correcting EFA deficiencies may be useful in reducing NASH severity.

Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor-ß2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti-inflammatory and anti-fibrotic effects of ω3 PUFA on NASH.

Real-time, in situ measurement of H2O generated during in situ combustion tests using 1f-normalized wavelength modulation spectroscopy with second harmonic detection.

The development and deployment of a real-time, in situ, non-invasive sensor to monitor the concentration of H 2 O during in situ combustion (ISC) experiments with a heavy-crude oil is described. A real-time sensor to monitor the gas-phase products from ISC can support the study of the kinetics of the complex chemical reactive system in ISC. The mole fraction of H 2 O was measured using tunable diode laser (TDL) absorption spectroscopy coupled with 1f-normalized wavelength modulation spectroscopy (WMS) and 2f detection. The WMS 2f/1f strategy was used to enhance sensitivity with effective noise rejection, particularly suitable when characterizing the water vapor evolved from oil-water emulsions. H 2 O was measured at 3934.10c m -1 from the fundamental band v 3. That transition was selected using the HITRAN database to increase the line strength and minimize interference from neighbor compounds. Measurements of H 2 O concentration were conducted at ambient temperature and pressure using a reference cell (H 2 O=2% at 98.6 kPa) to validate the sensor architecture under controlled laboratory environments. The TDL sensor was also successfully validated during real ISC experiments involving heavy-crude oil. Validation and combustion experiments showed the potential of the TDL-based sensor for non-invasive, real-time, in situ measurements of gas-phase species in conditions similar to those of laboratory-scale experimental ISC tests.

Effects of lipografts in immune-driven lipoatrophies. Case studies

Lipodystrophy is a pathological condition associated with an abnormal body adipose tissue redistribution. Facial lipoatrophy can be a consequence of congenital, acquired, or involutional. The lipograft is an autologous fat transplant, which constitutes a treatment option that provides volume, tissue regeneration, and advantages in relation to other fillers in autoimmune diseases. The aim is to highlight the filling action and the metabolic effect of facial lipotransfer, due to the grafted adipocytes survival, and the adipose tissue derived stem cells regenerative activity obtained by nano-fat in patients with facial lipoatrophy. Lipoinjection improves the architecture of the new dermis and increases its functional capacity. It is a treatment with autologous tissue (fatty graft) with great efficacy in relation to other alloplastic filler materials capable of exacerbating an inflammatory response mediated by antibody production.

La lipodistrofia es una condición patológica asociada a una redistribución anómala del tejido adiposo en el cuerpo. La lipoatrofia facial puede ser consecuencia de defectos congénitos, adquiridos o involutivos. El lipoinjerto es el trasplante de grasa autógena y constituye una opción de tratamiento que aporta volumen, regeneración tisular y ventajas en relación con otros materiales de relleno en enfermedades autoinmunes. Se busca resaltar la acción de relleno y el efecto metabólico de la lipotransferencia facial, por la supervivencia de los adipocitos injertados y la actividad regenerativa de las células madre provenientes del tejido adiposo obtenidas por nanofat en pacientes con lipoatrofia facial. La lipoinyección mejora la arquitectura de la nueva dermis y aumenta su capacidad funcional, es un tratamiento con tejido autógeno (injerto graso) con gran eficacia en relación con otros materiales de relleno aloplásticos capaces de exacerbar una respuesta inflamatoria mediada por la producción de anticuerpos.

A novel methodology for optimal location of reactive compensation through deep neural networks.

The present investigation proposes a methodology for the optimal location of reactive compensation in an electrical power system (EPS) through deep neural networks for voltage profile improvement. One of the main parameters to consider regarding EPS reliability is the voltage profile, a parameter that can be affected due to unexpected increases in impedance and loads in the system that translate as overloads in the system and an increase in the number of users. A voltage profile below the minimum or above the maximum accepted in the regulations of each country puts at risk the correct operation of equipment connected to the electrical network and, in turn, can cause economic losses and human lives (e.g by not guaranteeing reliability for hospitals and similar institutions). Economically, one of the most viable alternatives for improving voltage profiles is reactive compensation which in itself is carried out through capacitor banks. Therefore, this work proposes to find the correct location of capacitor banks in an electrical power system (using IEEE 14, 30 and 118 bus-bars systems as cases of study). In each system, the highest reactive load is identified, thus three values for reactive compensation are established as 80%, 50% and 25% of this maximum. Then, with these values, power flows are generated by locating each one of the reactive compensators' possible values in each one of the bars of the system, hence generating a large number of training data so that finally the neural network is capable of providing a quantitative classification highlighting which compensation and in which bus-bar produces the best result. The result is assessed by applying a modified standard deviation which evaluates the separation of the voltage profiles from the ideal desired value of 1pu.

GPR39 Deficiency Impairs Memory and Alters Oxylipins and Inflammatory Cytokines Without Affecting Cerebral Blood Flow in a High-Fat Diet Mouse Model of Cognitive Impairment.

Vascular cognitive impairment (VCI) is the second most common cause of dementia. There is no treatment for VCI, in part due to a lack of understanding of the underlying mechanisms. The G-protein coupled receptor 39 (GPR39) is regulated by arachidonic acid (AA)-derived oxylipins that have been implicated in VCI. Furthermore, GPR39 is increased in microglia of post mortem human brains with VCI. Carriers of homozygous GPR39 SNPs have a higher burden of white matter hyperintensity, an MRI marker of VCI. We tested the hypothesis that GPR39 plays a protective role against high-fat diet (HFD)-induced cognitive impairment, in part mediated via oxylipins actions on cerebral blood flow (CBF) and neuroinflammation. Homozygous (KO) and heterozygous (Het) GPR39 knockout mice and wild-type (WT) littermates with and without HFD for 8 months were tested for cognitive performance using the novel object recognition (NOR) and the Morris water maze (MWM) tests, followed by CBF measurements using MRI. Brain tissue and plasma oxylipins were quantified with high-performance liquid chromatography coupled to mass spectrometry. Cytokines and chemokines were measured using a multiplex assay. KO mice, regardless of diet, swam further away from platform location in the MWM compared to WT and Het mice. In the NOR test, there were no effects of genotype or diet. Brain and plasma AA-derived oxylipins formed by 11- and 15-lipoxygenase (LOX), cyclooxygenase (COX) and non-enzymatically were increased by HFD and GPR39 deletion. Interleukin-10 (IL-10) was lower in KO mice on HFD than standard diet (STD), whereas IL-4, interferon γ-induced protein-10 (IP-10) and monocyte chemotactic protein-3 (MCP-3) were altered by diet in both WT and KO, but were not affected by genotype. Resting CBF was reduced in WT and KO mice on HFD, with no change in vasoreactivity. The deletion of GPR39 did not change CBF compared to WT mice on either STD or HFD. We conclude that GPR39 plays a role in spatial memory retention and protects against HFD-induced cognitive impairment in part by modulating inflammation and AA-derived oxylipins. The results indicate that GPR39 and oxylipin pathways play a role and may serve as therapeutic targets in VCI.

Niveles de ascorbato en pacientes quemados durante la fase aguda / Ascorbate levels in burned patients during the acute phase

Introducción y objetivo: Después de la agresión térmica disminuyen los niveles de antioxidantes y se elevan los biomarcadores oxidativos, que junto a los mediadores inflamatorios, participan en las alteraciones de la microvasculatura provocando filtración capilar y shock hipovolémico. La vitamina C modula esta respuesta, por lo que se ha propuesto incorporarla en megadosis al tratamiento inicial del paciente quemado.El objetivo de este trabajo es estimar los niveles de ascorbato sérico que alcanzan los pacientes quemados administrando 3 g diarios de vitamina C durante la fase aguda.Material y método.Estudio descriptivo en 25 pacientes quemados en reanimación a los que se les determinó el nivel de ascorbato sin recibir la primera dosis de vitamina C y a las 72 horas de su administración. Comparamos las concentraciones de ascorbato en esos momentos con el de referencia empleando el Test de Student para una muestra. Determinamos si existía asociación entre el nivel de ascorbato y la extensión de la lesión utilizando el Test de Student para muestras independientes y analizamos el pronóstico de vida utilizando análisis de varianza (ANOVA).Resultados.Los valores promedio de ascorbato estuvieron significativamente disminuidos sin cambios entre el nivel inicial y a las 72 horas de tratamiento. No encontramos relación con la extensión ni con el pronóstico.Conclusiones.La administración de 3 g de vitamina C no fue suficiente para alcanzar los niveles séricos normales. Es necesario administrar dosis superiores a la protocolizada en nuestra institución. (AU)

Background and objective: After thermal aggression, antioxidant levels decrease and oxidative biomarkers rise, which together with inflammatory mediators, participate in alterations of the microvasculature, causing capillary leakage and hypovolemic shock. Vitamin C modulates this response, and it has been proposed to incorporate it in megadoses in the initial treatment of burned patients.The aim of this work is to estimate the serum ascorbate levels reached in burned patients by administering 3 g daily of vitamin C during the acute phase.Methods.Descriptive study in 25 burned patients in resuscitation, in whom the ascorbate level was determined without receiving the first dose of vitamin C and then at 72 hours. Those ascorbate concentrations were compared with the reference one using the Student's test for a sample. It was determined if there was an association between the level of ascorbate and the extension of the lesion using the Student's test for independent samples, and the same was analyzed with the prognosis of life using analysis of variance (ANOVA).Results.Mean ascorbate values were significantly decreased without changes between the initial level and that reached at 72 hours treatment. No relationship was found with the extension or with the prognosis.Conclusions.Administration of 3 g of vitamin C was not enough to reach normal serum levels. It is necessary to administer doses higher than the protocol established in our institution. (AU)

Lisado plaquetario homólogo como factor estimulante de la cicatrización en la zona donante de injertos / Homologous Platelet lysate as astimulatinghealing factor for the grafts donor area

Introducción: La búsqueda de alternativas para disminuir el tiempo de cicatrización y de hospitalización constituye uno de los aspectos fundamentales de la investigación actual. Los factores de crecimiento plaquetarios son capaces de potenciar la cicatrización. Objetivo: Determinar los beneficios de la aplicación del lisado de plaquetas homólogo sobre la zona donante del injerto autólogo de piel. Método: Se realizó un estudio longitudinal prospectivo en 20 pacientes tratados en el Hospital Hermanos Ameijeiras entre agosto de 2016 y mayo de 2019, que requirieron de injerto autólogo de piel en las zonas cruentas. Se realizaron dos tomas de injerto en el mismo paciente y región anatómica; una fue tratada con lisado plaquetario (zona de intervención) y otra con tratamiento convencional (zona control). La selección de pacientes fue intencional. Para estudiar las variables cualitativas se utilizaron números absolutos y proporciones y en las cuantitativas medidas de tendencia central y dispersión. Para la comparación de los resultados se aplicó la prueba de Friedman con un nivel de significación p ≤ 0,05. Resultados: La quemadura fue la principal causa de zona cruenta (75 por ciento), el grupo de edad más afectado fue el de mayores de 55 años. El porcentaje de cicatrización fue mayor en el grupo de intervención, con un tiempo de epitelización significativamente menor (p < 0,01), y el dolor en la zona intervenida fue menor. No hubo complicaciones. Conclusiones: Los beneficios encontrados en la zona intervenida con lisado plaquetario fueron significativos con una cicatrización más rápida y menor dolor(AU)

Introduction: The search for treatment alternatives that allow reducing wound healing and hospitalization time are fundamental aspects in research nowadays. Platelet growth factors are capable of enhancing wound healing. Objective: Determine the benefits of applying homologous platelet lysate on the donor area of autologous skin graft. Methods: A prospective longitudinal-section study was conducted in 20 patients with bloody areas that required autologous skin graft at the Hospital Hermanos Ameijeiras between August 2016 and May 2019. Two graft intakes were made in the same patient and anatomical region, one of them treated with platelet lysate (intervention zone) and one with conventional treatment (control zone). Patients selection was intentional. Absolute numbers and proportions were used to study the qualitative variables, and measures of central tendency and dispersion were used in the quantitative variables. To compare de results, the Friedman test was applied, setting a level of significance p < 0,05. Results: The main cause of bloody area was burns (75 percent), the most affected age group was those over 55 years, the healing percentage was greater in the intervention group with a statistically significant shorter epithelization time (p < 0,01) and there was less pain in the intervention zone. There were no complications. Conclusions: The benefits found in the intervened area with platelet lysate were significant with faster healing and less pain(AU)

Plasma Oxylipins: A Potential Risk Assessment Tool in Atherosclerotic Coronary Artery Disease.

Background: While oxylipins have been linked to coronary artery disease (CAD), little is known about their diagnostic and prognostic potential. Objective: We tested whether plasma concentration of specific oxylipins may discriminate among number of diseased coronary arteries and predict median 5-year outcomes in symptomatic adults. Methods: Using a combination of high-performance liquid chromatography (HPLC) and quantitative tandem mass spectrometry, we conducted a targeted analysis of 39 oxylipins in plasma samples of 23 asymptomatic adults with low CAD risk and 74 symptomatic adults (≥70% stenosis), aged 38-87 from the Greater Portland, Oregon area. Concentrations of 22 oxylipins were above the lower limit of quantification in >98% of adults and were compared, individually and in groups based on precursors and biosynthetic pathways, in symptomatic adults to number of diseased coronary arteries [(1) n = 31; (2) n = 23; (3) n = 20], and outcomes during a median 5-year follow-up (no surgery: n = 7; coronary stent placement: n = 24; coronary artery bypass graft surgery: n = 26; death: n = 7). Results: Plasma levels of six quantified oxylipins decreased with the number of diseased arteries; a panel of five oxylipins diagnosed three diseased arteries with 100% sensitivity and 70% specificity. Concentrations of five oxylipins were lower and one oxylipin was higher with survival; a panel of two oxylipins predicted survival during follow-up with 86% sensitivity and 91% specificity. Conclusions: Quantification of plasma oxylipins may assist in CAD diagnosis and prognosis in combination with standard risk assessment tools.

Cancer of the anal canal, a reality in the Colombian coffee region. Clinical-epidemiological review 2000-2019.

INTRODUCTION: Anal cancer is a rare pathology which has increased over the last few decades, and, therefore, gained importance for the quality of life of affected individuals. Thus, a review has been conducted in the Colombian coffee region (Departments of Caldas, Quindío y Risaralda) describing its behaviour and clinical-epidemiological profile. MATERIALS AND METHODS: Descriptive review of 437 patients of Western SAS Oncologists between January 2000 and December 2019 with a diagnosis of anal cancer. RESULTS: 62% of cases presented in women with a median age of 62 years, 30% in the sixth decade; centred at 65% in three main cities designated as capitals (Manizales, Pereira and Armenia); 62% as localised disease, with 40% stage II-A and 6% as initial metastasis; 29% presented positive ganglia, particularly N1a; squamous cell or epidermoid histology in 90%; 16% poorly differentiated; 5% related to Human Immunodeficiency Virus infection; localisation in the medial area of the anal canal in 63% of cases; 83% completed treatment, and 92% of them received chemotherapy/radiation therapy with 87% based on the Nigro protocol; finally, 11% presented with relapse in the liver in 10% of cases and 55% local. CONCLUSION: Four hundred and thirty-seven patients evaluated over 20 years with follow up at median 34.13 months (standard deviation 41.75) with median survival at later ages decreasing to 62% in patients older than 80 years, and differences in survival in localised disease at 78% in comparison to 46% in advanced metastasis. Finally, the overall 5-year survival rate is 69% with a median survival of 191 months in the study.

A novel algorithm for high compression rates focalized on electrical power quality signals.

This research proposes a high-performance algorithm for the compression rate of electrical power quality signals, using wavelet transformation. To manage the massive amount of data the telecommunications networks are constantly acquiring it is necessary to study techniques for data compression, which will save bandwidth and reduce costs extensively by avoiding having massive data storage facilities. First biorthogonal wavelet level six transform is applied, however after compression, the reconstructed signal will have a different amplitude and it will be shifted when compared to the original one. Then, normalization is used (for amplitude correction between the original signal and reconstructed one) by multiplying the reconstructed signal by the result of the division between the original signal maximum magnitude and the reconstructed signal maximum magnitude. Thirdly, the ripple in the reconstructed signal is eliminated by applying a moving average filter. Finally, the shifting is corrected by finding the difference between the maximum points in a cycle of the original signal and the reconstructed one. After the compression algorithm was performed the best rates are 99.803% for compression rate, RTE 99.9479%, NMSE 0.000434, and Cross-Correlation 0.999925. Finally, this works presents two new performance criteria, compression time and recovery time, both of them in a real scenario will determinate how fast the algorithm can perform.

Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes.

Western diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes (T2D) with gut microbiota playing an important role in modulating effects of the diet. Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism. Interrogation of this network pointed to taxa with potential beneficial or harmful effects on host's metabolism. We then validate the functional role of the predicted bacteria in regulating metabolism and show that they act via different host pathways. Our gene expression and electron microscopy studies show that two species from Lactobacillus genus act upon mitochondria in the liver leading to the improvement of lipid metabolism. Metabolomics analyses revealed that reduced glutathione may mediate these effects. Our study identifies potential probiotic strains for T2D and provides important insights into mechanisms of their action.

Centella asiatica Alters Metabolic Pathways Associated With Alzheimer's Disease in the 5xFAD Mouse Model of ß-Amyloid Accumulation.

Centella asiatica is an herb used in Ayurvedic and traditional Chinese medicine for its beneficial effects on brain health and cognition. Our group has previously shown that a water extract of Centella asiatica (CAW) elicits cognitive-enhancing effects in animal models of aging and Alzheimer's disease, including a dose-related effect of CAW on memory in the 5xFAD mouse model of ß-amyloid accumulation. Here, we endeavor to elucidate the mechanisms underlying the effects of CAW in the brain by conducting a metabolomic analysis of cortical tissue from 5xFAD mice treated with increasing concentrations of CAW. Tissue was collected from 8-month-old male and female 5xFAD mice and their wild-type littermates treated with CAW (0, 200, 500, or 1,000 mg/kg/d) dissolved in their drinking water for 5 weeks. High-performance liquid chromatography coupled to high-resolution mass spectrometry analysis was performed and relative levels of 120 annotated metabolites were assessed in the treatment groups. Metabolomic analysis revealed sex differences in the effect of the 5xFAD genotype on metabolite levels compared to wild-type mice, and variations in the metabolomic response to CAW depending on sex, genotype, and CAW dose. In at least three of the four treated groups (5xFAD or wild-type, male or female), CAW (500 mg/kg/d) significantly altered metabolic pathways related to purine metabolism, nicotinate and nicotinamide metabolism, and glycerophospholipid metabolism. The results are in line with some of our previous findings regarding specific mechanisms of action of CAW (e.g., improving mitochondrial function, reducing oxidative stress, and increasing synaptic density). Furthermore, these findings provide new information about additional, potential mechanisms for the cognitive-enhancing effect of CAW, including upregulation of nicotinamide adenine dinucleotide in the brain and modulation of brain-derived neurotrophic factor. These metabolic pathways have been implicated in the pathophysiology of Alzheimer's disease, highlighting the therapeutic potential of CAW in this neurodegenerative disease.

Nitrate and nitrite exposure leads to mild anxiogenic-like behavior and alters brain metabolomic profile in zebrafish.

Dietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. We tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We utilized targeted and untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to examine the extent to which treatment resulted in changes in nitrate or nitrite concentrations in the brain and altered the brain metabolome. Fish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2-4 weeks and free swim, startle response, and shuttle box assays were performed. Nitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment was associated with mild anxiogenic-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted metabolomics analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. Untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment. Overall, the depletion in brain metabolites is plausibly associated with the regulation of neuronal activity including statistically significant reductions in the inhibitory neurotransmitter γ-aminobutyric acid (GABA; 18-19%), and its precursor, glutamine (17-22%). Nitrate treatment caused significant depletion in the brain concentration of fatty acids including linoleic acid (LA) by 50% and arachidonic acid (ARA) by 80%; nitrite treatment caused depletion of LA by ~90% and ARA by 60%, change which could alter the function of dopaminergic neurons and affect behavior. Nitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health. It is plausible that indirect NO-mediated mechanisms may be responsible for the nitrate and nitrite-mediated effects on the brain metabolome and behavior in zebrafish.

Temozolamide as an adjuvant in glioblastoma. How long? The experience of a cancer center in Colombia / Temozolamide como adyuvancia en glioblastoma. ¿Por cuánto tiempo?. Experiencia en un centro oncológico de Colombia

Abstract Introduction: glioblastoma multiforme is considered to be highly lethal, for which the optimal duration of adjuvant temozolamide chemotherapy has not been determined. Objective: to evaluate survival according to the length of adjuvant chemotherapy based on the standard Stupp platform protocol. Materials and methods: a retrospective cohort analysis of 299 high-grade central nervous system tumors seen at Oncólogos del Occidente, focused solely on glioblastoma multiforme, according to clinical, treatment and outcome variables. Results: one hundred ninety-three patients with glioblastoma; 84 (44%) received standard Stupp platform treatment; mean age 54 years; 55% males; mean tumor size 28,793 mm2; 48% right hemisphere; 21% crossed the midline; 33% had seizures and 42% neurological deficit; 55% Karnofsky less than 70% and 66% RPA IV classification; 77% received radiation with 60.00 Gy or more; 19% had complications; 79% partial resection and 12% total resection; 77% relapsed; at closure, 57% were alive, global survival of 26% and mean of 26 months, with a difference of 31 months for adjuvance of <or> 6 months and 30 months for adjuvance of <or> 12 months, without reaching a median in the 18 and 24 month groups, all of them favoring the group with the longest time. Conclusion: a clear increase in survival is shown with adjuvant temozolamide for periods longer than six months, as well as a tendency towards better results with increased duration of adjuvance.

Resumen Introducción: el glioblastoma multiforme se considera altamente letal, donde la duración óptima de quimioterapia adyuvante con base en temozolamide no ha sido definida. Objetivo: evaluar la sobrevida según la duración de quimioterapia adyuvante basada en el esquema estándar de plataforma Stupp. Material y métodos: análisis de cohorte retrospectiva de 299 tumores del sistema nervioso central de alto grado, valorados en Oncólogos del Occidente enfocado sólo a glioblastoma multiforme según variables clínicas, terapéuticas y de resultados. Resultados: ciento noventa y tres pacientes con glioblastoma, 84 (44%) recibieron manejo estándar tipo plataforma Stupp; edad media 54 años; hombres 55%; tamaño tumoral medio 28.79 mm2; hemisferio derecho 48%; 21% cruzaban línea media; 33% presentaron convulsiones y 42% déficit neurológico; 55% Karnofsky menor a 70% y 66% clasificación RPA IV; 77% recibieron radioterapia con 60.00 Gys o mayor; 19% presentaron complicaciones; resección parcial 79% y 12% total; 77% recayeron; al cierre 57% se encontraban vivos, sobrevida global de 26% y media de 26 meses con diferencia de 31 meses para adyuvancia en <o> a 6 meses y 30 meses en adyuvancia <o> a 12 meses sin alcanzar mediana en los grupos <o> de 18 y 24 meses favoreciendo en todos al grupo de mayor tiempo. Conclusión: se demuestra aumento claro en la sobrevida con el empleo de temozolamide adyuvante por periodos mayores a seis meses y una tendencia a mejores resultados mientras mayor sea el tiempo de adyuvancia.

An examination of the role of biochar and biochar water-extractable substances on the sorption of ionizable herbicides in rice paddy soils.

The application of biochar as a soil amendment can increase concentrations of soil organic matter, especially water-extractable organic substances. Due to their mobility and reactivity, more studies are needed to address the potential impact of biochar water-extractable substances (BWES) on the sorption of herbicides in agricultural soils that are periodically flooded. Two paddy soils (100 and 700 years of paddy soil development), unamended or amended with raw (BC) or washed biochar (BCW), were used to test the influence of BWES on the sorption behavior of the herbicides azimsulfuron (AZ) and penoxsulam (PE). The adsorption of AZ to biochar was much stronger than that to the soils, and it was adsorbed to a much larger extent to BC than to BCW. The depletion of polar groups in the BWES from the washed biochar reduced AZ adsorption but had no effect on PE adsorption. The adsorption of AZ increased when the younger soil (P100) was amended with BC and decreased when it was amended with BCW. In P700, which has lower dissolved organic carbon (DOC) content than P100, the adsorption of AZ increased regardless of whether biochar was raw or washed. The adsorption of PE slightly decreased when P100 was amended with BC or BCW and slightly increased when P700 was amended with BC or BCW. In order to evaluate compositional differences in the biochar and BWES before and after the washing treatment, we performed solid-state 13C NMR spectroscopy of BC and BCW, and high resolution mass spectrometry of BWES. Our observations stress the importance of proper consideration of soil and biochar properties before their incorporation into paddy soils, since biochar may reduce or increase the mobility of AZ and PE depending on soil properties and time of application.

A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice.

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the western diet (WD) is a major contributor to the onset and progression of these chronic diseases. Our aim was to use a lipidomic approach to identify potential lipid mediators of diet-induced NASH. We previously used a preclinical mouse (low density lipoprotein receptor null mouse, Ldlr -/-) model to assess transcriptomic mechanisms linked to WD-induced NASH and docosahexaenoic acid (DHA, 22:6, ω3)-mediated remission of NASH. This report used livers from the previous study to carry out ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography coupled with dynamic multi-reaction monitoring (HPLC-dMRM) to assess the impact of the WD and DHA on hepatic membrane lipid and oxylipin composition, respectively. Feeding mice the WD increased hepatic saturated and monounsaturated fatty acids and arachidonic acid (ARA, 20:4, ω6) in membrane lipids and suppressed ω3 polyunsaturated fatty acids (PUFA) in membrane lipids and ω3 PUFA-derived anti-inflammatory oxylipins. Supplementing the WD with DHA lowered hepatic ARA in membrane lipids and ARA-derived oxylipins and significantly increased hepatic DHA and its metabolites in membrane lipids, as well as C20-22 ω3 PUFA-derived oxylipins. NASH markers of inflammation and fibrosis were inversely associated with hepatic C20-22 ω3 PUFA-derived Cyp2C- and Cyp2J-generated anti-inflammatory oxylipins (false discovery rate adjusted p-value; q ≤ 0.026). Our findings suggest that dietary DHA promoted partial remission of WD-induced NASH, at least in part, by lowering hepatic pro-inflammatory oxylipins derived from ARA and increasing hepatic anti-inflammatory oxylipins derived from C20-22 ω3 PUFA.

Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish.

BACKGROUND: Dietary nitrate improves exercise performance by reducing the oxygen cost of exercise, although the mechanisms responsible are not fully understood. OBJECTIVES: We tested the hypothesis that nitrate and nitrite treatment would lower the oxygen cost of exercise by improving mitochondrial function and stimulating changes in the availability of metabolic fuels for energy production. METHODS: We treated 9-mo-old zebrafish with nitrate (sodium nitrate, 606.9 mg/L), nitrite (sodium nitrite, 19.5 mg/L), or control (no treatment) water for 21 d. We measured oxygen consumption during a 2-h, strenuous exercise test; assessed the respiration of skeletal muscle mitochondria; and performed untargeted metabolomics on treated fish, with and without exercise. RESULTS: Nitrate and nitrite treatment increased blood nitrate and nitrite levels. Nitrate treatment significantly lowered the oxygen cost of exercise, as compared with pretreatment values. In contrast, nitrite treatment significantly increased oxygen consumption with exercise. Nitrate and nitrite treatments did not change mitochondrial function measured ex vivo, but significantly increased the abundances of ATP, ADP, lactate, glycolytic intermediates (e.g., fructose 1,6-bisphosphate), tricarboxylic acid (TCA) cycle intermediates (e.g., succinate), and ketone bodies (e.g., ß-hydroxybutyrate) by 1.8- to 3.8-fold, relative to controls. Exercise significantly depleted glycolytic and TCA intermediates in nitrate- and nitrite-treated fish, as compared with their rested counterparts, while exercise did not change, or increased, these metabolites in control fish. There was a significant net depletion of fatty acids, acyl carnitines, and ketone bodies in exercised, nitrite-treated fish (2- to 4-fold), while exercise increased net fatty acids and acyl carnitines in nitrate-treated fish (1.5- to 12-fold), relative to their treated and rested counterparts. CONCLUSIONS: Nitrate and nitrite treatment increased the availability of metabolic fuels (ATP, glycolytic and TCA intermediates, lactate, and ketone bodies) in rested zebrafish. Nitrate treatment may improve exercise performance, in part, by stimulating the preferential use of fuels that require less oxygen for energy production.