RESUMEN

BACKGROUND: Swallowing dysfunction (dysphagia) significantly impacts patient and medical outcomes. In Sweden, there is no comprehensive outcome measure for dysphagia that incorporates holistic assessment and dysphagia impact on a person's impairment, function and participation. The Dysphagia Outcome and Severity Scale (DOSS) was developed and validated (in English) and incorporates the World Health Organisation's (WHO) aforementioned, International Classification of Functioning (ICF) aspects. This study translated then evaluated the validity and reliability of the Swedish version, DOSS-S. METHOD: Translation occurred based on WHO recommendations. The Content Validity Index (CVI) of the translated version (DOSS-S) was assessed twice by 11 (multi-professional) dysphagia experts. Criterion validity and rater reliability was calculated using 18 Speech Pathologists assessing patient cases from International Dysphagia Diet Standardization Initiative-Functional Diet Scale (IDDS-FDS) research. RESULTS: Very high CVI values (0.96-0.99) for the linguistic correlation, and high CVI values (0.84-0.94) for applicability correlation were achieved. High criterion validity of DOSS-S with IDDSI-FDS was demonstrated (rs = 0.89, p < 0.01), with very high inter and intra rater reliabilities (ICC > 0.90). CONCLUSION: The DOSS-S demonstrated very high validity values, and very high inter and intra rater reliability. This research contributes to improved dysphagia management by providing interprofessional dysphagia clinicians with a validated scale to identify patient progression, communicate dysphagia status between regions and countries, and document patient outcomes using an ICF framework.

Asunto(s)

RESUMEN

Due to the relatively high concentrations of polycyclic aromatic hydrocarbons (PAHs) in oil samples, oil spills in aquatic ecosystems release significant amounts of PAHs. Although remediation efforts often take place during or immediately after an oil spill incident, a portion of the released PAHs remains in the body of water. A natural phenomenon resulting from the direct exposure of PAHs to sunlight is photodegradation. This article investigates the effect of dioctyl sulfosuccinate (DOSS) on the photodegradation of benzo[a]pyrene (BaP), the most toxic PAH in the priority pollutants list of the US Environmental Protection Agency (EPA). DOSS is a surfactant typically used in the remediation of oil spills. Three lamps with maximum emission wavelengths at 350 nm, 419 nm, and 575 nm were individually and simultaneously used to irradiate aqueous solutions of BaP in the absence and the presence of DOSS. When irradiated with the 419 nm lamp or the 575 lamp, BaP showed no photodegradation. Upon irradiation with the 350 nm lamp and with the simultaneous use of the three lamps, the photodegradation of BaP followed first-order kinetics. Independent of the irradiation wavelength, the presence of DOSS increased the half-life of BaP in the aqueous solution. In the case of the 350 nm lamp, the rate constant of photodegradation in the absence and the presence of DOSS varied from (3.79 ± 0.97) × 10-3 min-1 to (1.10 ± 0.13) × 10-3 min-1, respectively. Under simultaneous irradiation with the lamps, the rate constant of photodegradation varied from (1.12 ± 0.35) × 10-3 min (no DOSS) to (3.30 ± 0.87) × 10-4 (with DOSS). Since the largest rate constants of photodegradation were observed in the absence of DOSS, the longer half-lives of BaP in the presence of surfactant were attributed to the incorporation of PAH molecules into the DOSS micelles.

RESUMEN

In many jurisdictions, dispersants are included in contingency plans as a viable countermeasure that can help reduce the overall environmental impact of marine oil spills. When used, it is imperative to monitor the progression of dispersant and oil to assess their environmental fate and behaviour. Amphiphilic salt dioctyl sodium sulfosuccinate (DOSS) is the major effective component of the most commonly available dispersants, such as Corexit® EC9500A. Without proper sample preparation, dispersed oil in water samples could interfere with the accurate analysis of DOSS and easily contaminate the LC-MS system. In this work, solid phase extraction (SPE) weak anion exchange (WAX) cartridges were used to separate oil and DOSS in aqueous samples. DOSS was accurately determined by liquid chromatography coupled with a high resolution Orbitrap mass spectrometer (LC-HRMS). Oil fingerprinting analysis was conducted and total petroleum hydrocarbons (TPHs), polycyclic aromatic hydrocarbons (PAHs), and petroleum biomarkers were determined by gas chromatography-flame ionization detection (GC-FID) and mass spectrometry (GC-MS). This SPE-LC/GC-MS method was used for the analysis of oil-dispersant water samples containing a mixture of Corexit® EC9500A and a selection of crude oils and refined petroleum products. Nearly a 100% DOSS recovery was obtained for various oil-surfactant conditions. Parallel quantitation of oils with dispersants was achieved using this method. A portion of the TPH loss was possibly attributed to oil retained by the SPE column. Chemical fingerprints and diagnostic ratios of target compounds in recovered dispersed oil overall remain unchanged compared with those of all studied oils.

Asunto(s)

RESUMEN

AIMS: A recent review identified 19 anticholinergic burden scales (ABSs) but no study has yet compared the impact of all 19 ABSs on delirium. We evaluated whether a high anticholinergic burden as classified by each ABS is associated with incident delirium. METHOD: We performed a retrospective cohort study in a Swiss tertiary teaching hospital using data from 2015-2018. Included were patients aged ≥65, hospitalised ≥48 hours with no stay >24 hours in intensive care. Delirium was defined twofold: (i) ICD-10 or CAM and (ii) ICD-10 or CAM or DOSS. Patients' cumulative anticholinergic burden score, calculated within 24 hours after admission, was classified using a binary (<3: low, ≥3: high burden) and a categorical approach (0: no, 0.5-3: low, ≥3: high burden). Association was analysed using multivariable logistic regression. RESULTS: Over 25 000 patients (mean age 77.9 ± 7.6 years) were included. Of these, (i) 864 (3.3%) and (ii) 2770 (11.0%) developed delirium. Depending on the evaluated ABS, 4-63% of the patients were exposed to at least one anticholinergic drug. Out of 19 ABSs, (i) 14 and (ii) 16 showed a significant association with the outcomes. A patient with a high anticholinergic burden score had odds ratios (ORs) of 1.21 (95% confidence interval [CI]: 1.03-1.42) to 2.63 (95% CI: 2.28-3.03) for incident delirium compared to those with low or no burden. CONCLUSION: A high anticholinergic burden within 24 hours after admission was significantly associated with incident delirium. Although prospective studies need to confirm these results, discontinuing or substituting drugs with a score of ≥3 at admission might be a targeted intervention to reduce incident delirium.

Asunto(s)

RESUMEN

Mycobacterium tuberculosis (Mtb) senses and responds to host-derived gasotransmitters NO and CO via heme-containing sensor kinases DosS and DosT and the response regulator DosR. Hydrogen sulfide (H2S) is an important signaling molecule in mammals, but its role in Mtb physiology is unclear. We have previously shown that exogenous H2S can modulate expression of genes in the Dos dormancy regulon via an unknown mechanism(s). Here, we test the hypothesis that Mtb senses and responds to H2S via the DosS/T/R system. Using UV-Vis and EPR spectroscopy, we show that H2S binds directly to the ferric (Fe3+) heme of DosS (KDapp = 5.30 µM) but not the ferrous (Fe2+) form. No interaction with DosT(Fe2+-O2) was detected. We found that the binding of sulfide can slowly reduce the DosS heme iron to the ferrous form. Steered Molecular Dynamics simulations show that H2S, and not the charged HS- species, can enter the DosS heme pocket. We also show that H2S increases DosS autokinase activity and subsequent phosphorylation of DosR, and H2S-mediated increases in Dos regulon gene expression is lost in Mtb lacking DosS. Finally, we demonstrate that physiological levels of H2S in macrophages can induce DosR regulon genes via DosS. Overall, these data reveal a novel mechanism whereby Mtb senses and responds to a third host gasotransmitter, H2S, via DosS(Fe3+). These findings highlight the remarkable plasticity of DosS and establish a new paradigm for how bacteria can sense multiple gasotransmitters through a single heme sensor kinase.

Asunto(s)

RESUMEN

Dioctyl Sodium Sulfosuccinate (DOSS, CAS 577-11-7) is a chemical emulsifying surfactant that is widely used in the food and the cosmetic industry, and it is also the major component of the crude oil chemical dispersant Corexit™. Despite of its wide use, the studies related to its negative effect have been evaluated mainly in marine environments showing that DOSS is highly bioactive, extremely low volatile, and potential to persist in the environment longer than other dispersant components. Up to date, there is no available information of DOSS concentration in freshwater environments, little is known about its downstream fate after excretion and its effect on freshwater organisms. The objective of this study was to evaluate the effect of DOSS at different concentrations in embryos and adults of zebrafish Danio rerio in an acute-static bioassays of 96 h. The median lethal concentration in embryos was 33.3 mg/L. Malformations started to be observed at 10 mg/L. In adults, the gene expression analysis in gill tissues showed a deregulation in genes associated with the antioxidant system and the nucleotide excision repair mechanism. Additionally, Micronuclei (DNA damage) in erythrocytes, and fat degeneration in liver, hypertrophy and hyperplasia in gills, and hyaline drops in kidney tissues were also observed. In conclusion, the concentrations of DOSS evaluated here would be of health relevance to fish based on morphological alterations in embryos and changes in the gene expression profile, DNA damage and tissue impairment in adults.

Asunto(s)

RESUMEN

BACKGROUND/OBJECTIVES: Detecting delirium is important to identify patients with a high risk of poor outcomes. Although many different kinds of screening instruments for delirium exist, there is no solid consensus about which methods are the most effective. In addition, it is important to find the most useful tools in predicting outcomes such as mortality. DESIGN: Retrospective cohort study. SETTING: University of Iowa Hospitals and Clinics. PARTICIPANTS: A total of 1,125 adult inpatients (mean age = 67.7; median age = 69). MEASUREMENTS: Post hoc analyses were performed based on existing data from the Confusion Assessment Method for Intensive Care Unit (CAM-ICU), Delirium Rating Scale-Revised-98 (DRS), and the Delirium Observation Screening Scale (DOSS). Correlation among these scales and relationships between 365-day mortality and each scale were evaluated. RESULTS: A positive result on the CAM-ICU ("CAM-ICU positive") was associated with higher DRS and DOSS scores. A DRS score = 9/10 was the best cutoff to detect CAM-ICU positive, and DOSS = 2/3 was the best cutoff to detect CAM-ICU positive. CAM-ICU positive was associated with high 365-day mortality. DRS score = 9/10 and DOSS score = 0/1 were found to differentiate mortality risk the most significantly. Higher DRS and DOSS scores significantly coincided with a decrease in a patient's survival rate at 365 days. CONCLUSION: The best DRS and DOSS cutoff scores to differentiate 365-day mortality risk were lower than those commonly used to detect delirium in the literature. New cutoff scores for the DRS and DOSS might be useful in differentiating risk of mortality among hospital patients.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: The accurate identification of the exon/intron boundaries is critical for the correct annotation of genes with multiple exons. Donor and acceptor splice sites (SS) demarcate these boundaries. Therefore, deriving accurate computational models to predict the SS are useful for functional annotation of genes and genomes, and for finding alternative SS associated with different diseases. Although various models have been proposed for the in silico prediction of SS, improving their accuracy is required for reliable annotation. Moreover, models are often derived and tested using the same genome, providing no evidence of broad application, i.e. to other poorly studied genomes. RESULTS: With this in mind, we developed the Splice2Deep models for SS detection. Each model is an ensemble of deep convolutional neural networks. We evaluated the performance of the models based on the ability to detect SS in Homo sapiens, Oryza sativa japonica, Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans. Results demonstrate that the models efficiently detect SS in other organisms not considered during the training of the models. Compared to the state-of-the-art tools, Splice2Deep models achieved significantly reduced average error rates of 41.97% and 28.51% for acceptor and donor SS, respectively. Moreover, the Splice2Deep cross-organism validation demonstrates that models correctly identify conserved genomic elements enabling annotation of SS in new genomes by choosing the taxonomically closest model. CONCLUSIONS: The results of our study demonstrated that Splice2Deep both achieved a considerably reduced error rate compared to other state-of-the-art models and the ability to accurately recognize SS in other organisms for which the model was not trained, enabling annotation of poorly studied or newly sequenced genomes. Splice2Deep models are implemented in Python using Keras API; the models and the data are available at https://github.com/SomayahAlbaradei/Splice_Deep.git.

RESUMEN

Observations made for the analysis of the oil spill dispersant tracer dioctyl sulfosuccinate (DOSS) during LC50 toxicity testing, highlighted a stability issue for this tracer compound in seawater. A liquid chromatography high-resolution quadrupole time-of-flight mass spectrometry (LC/QToF) was used to confirm monooctyl sulfosuccinate (MOSS) as the only significant DOSS breakdown product, and not the related isomer, 4-(2-ethylhexyl) 2-sulfobutanedioate. Combined analysis of DOSS and MOSS was shown to be applicable to monitoring of spill dispersants Corexit® EC9500A, Finasol OSR52, Slickgone NS, and Slickgone EW. The unassisted conversion of DOSS to MOSS occurred in all four oil spill dispersants solubilized in seawater, although differences were noted in the rate of MOSS formation. A marine microcosm study of Corexit EC9500A, the formulation most rapid to form MOSS, provided further evidence of the stoichiometric conversion of DOSS to MOSS under conditions relevant to real world dilbit spill. Results supported combined DOSS and MOSS analysis for the monitoring of spill dispersant in a marine environment, with a significant extension of sample collection time by 10 days or longer in cooler conditions. Implications of the unassisted formation of MOSS and combined DOSS:MOSS analysis are discussed in relation to improving dispersant LC50 toxicity studies.

Asunto(s)

RESUMEN

The DevR-DevS/DosR-DosS two-component system of Mycobacterium tuberculosis, that comprises of DevS sensor kinase and DevR response regulator, is essential for bacterial adaptation to hypoxia by inducing dormancy regulon expression. The dominant phosphatase activity of DevS under aerobic conditions enables tight negative control, whereas its kinase function activates DevR under hypoxia to induce the dormancy regulon. A net balance in these opposing kinase and phosphatase activities of DevS calibrates the response output of DevR. To gain mechanistic insights into the kinase-phosphatase balance of DevS, we generated alanine substitution mutants of five residues located in DHp α1 helix of DevS, namely Phe-403, Gly-406, Leu-407, Gly-411 and His-415. For the first time, we have identified kinase positive phosphatase negative (K+P-) mutants in DevS by a single-site mutation in either Gly-406 or Leu-407. M. tuberculosis Gly-406A and Leu-407A mutant strains constitutively expressed the DevR regulon under aerobic conditions despite the presence of negative signal, oxygen. These mutant proteins exhibited ∼2-fold interaction defect with DevR. We conclude that Gly-406 and Leu-407 residues are individually essential for the phosphatase function of DevS. Our study provides new insights into the negative control mechanism of DevS by demonstrating the importance of an optimal interaction between DevR and DevS, and local changes associated with individual residues, Gly-406 and Leu-407, which mimic ligand-free DevS. These K+P- mutant strains are expected to facilitate the rapid aerobic screening of DevR antagonists in M. tuberculosis, thereby eliminating the requirement for hypoxic culture conditions.

Asunto(s)

RESUMEN

BACKGROUND: Delirium in the hospitals leads to worse outcomes for patients. There were no previous studies that characterize patients with delirium from multiple hospital locations. OBJECTIVE: To describe patient characteristics screening positive for delirium and identify any correlations with hospital location and medication use. DESIGN, SETTINGS, PATIENTS: Retrospective chart review of 227 hospitalized patients from a large, academic, tertiary referral, 2-campus health system. Patients were ≥18 years old and had delirium for at least ≥24 hours. Validated delirium screening tools were utilized. MEASUREMENTS: Patients' demographics, inpatient stay information, delirium episodes characteristics, drugs, and palliative and psychiatry teams' involvement. RESULTS: Most patients were older with a mean age of 64.1 years. The most common primary diagnoses were infection, cardiac, and pulmonary. Average length of delirium was 7.2 days (standard deviation [SD] = 8.2), and average length of stay (LOS) was 18.7 days (median = 10.5, SD = 35.1, 95% confidence interval = 14.1-23). Thirty-day readmission rate was 24.8% (65/262 hospitalizations); 12.8% of patients died in the hospital (29/227). Around one-third of hospitalizations had involvement of palliative care, palliative psychiatry, or general psychiatry team. There was a decrease in the number of medications administered 24 hours after the first recording of delirium compared to the immediate preceding 48 hours. Those hospitalizations where delirium first occurred in the intensive care unit (ICU) did have a longer LOS (average = 22.9, SD = 45.7) than those where delirium first occurred outside the ICU (average = 14.8, SD = 20.5). Patients were likely to have received an opioid within 48 hours in 51% of hospitalizations and to have received benzodiazepines in 16% of hospitalizations. CONCLUSION: In our study, we found that delirium significantly impacted length of delirium episode, number of episodes of delirium, length of hospital admission, and mortality. The population most sensitive to the impacts of delirium were elderly patients.

Asunto(s)

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.

Asunto(s)

RESUMEN

OBJECTIVES: Abnormal swallowing or dysphagia is a potentially fatal symptom in Parkinson's disease (PD) and is characterized by frequent silent aspiration, which is an unrecognized risk for aspiration pneumonia. While the effects of oral levodopa on swallowing functions remain controversial, several small-scale studies have reported that rotigotine transdermal patch seems effective. The different effects between levodopa and rotigotine may be attributed to continuous dopaminergic stimulation (CDS), however, the absence of direct comparative evidence precludes conclusion. METHODS: In the present retrospective open-label study of 50 patients with PD, swallowing functions were assessed via videofluoroscopic (VF) examination before and after treatment. Treatment included 2 mg/day rotigotine transdermal patch (N = 29) or 200 mg/day oral levodopa with carbidopa (N = 21) in drug-naïve and add-on groups of patients. RESULTS: Rotigotine more consistently improved all measures assessed via VF examination. Such effects were similar to those in the drug-naïve and add-on groups. Improvement and responder rates of certain measures were significantly higher in the rotigotine group than in the levodopa group. CONCLUSIONS: Our finding that rotigotine (levodopa equivalent dose = 60 mg) was more consistently effective than 200 mg/day oral levodopa suggests that CDS is more important in improving swallowing functions.

Asunto(s)

RESUMEN

Tuberculosis is one of the oldest known infectious diseases, responsible for millions of deaths annually around the world. The ability of Mycobacterium tuberculosis (Mtb) to enter into a dormant state has been considered integral to the success of this bacterium as a human pathogen. One of the key systems involved in regulating the entrance into dormancy is the differentially expressed in virulent strain sensor protein (DevS) [(dormancy survival sensor protein (DosS)]. However, the physiological signal for DevS has remained unclear since it was first shown to be a heme-based sensor with conflicting reports on whether it is a redox or an oxygen sensor. To address this question and provide a better understanding of the electronic properties of this protein, we present here, for the first time, a series of spectroelectrochemistry measurements of the full-length holo DevS in anaerobic conditions as well as bound to CO, NO, imidazole (Imz), cyanide, and O2 . An interesting feature of this protein is its ability to bind Imz even in the ferrous state, implying small-molecule analogues could be designed as potential regulators. Nonetheless, a midpoint potential (Em ) value of +10 mV [vs normal hydrogen electrode (NHE)] for DevS as measured under anaerobic conditions is much higher than the expected cytosolic potential for Mtb or even within stimulated macrophages (~ -270 mV vs NHE), indicating this sensor works in a reduced ferrous state. These data, along with the high oxygen affinity and very slow auto-oxidation rate of DevS, provides evidence that it is not a redox sensor. Overall, this study validates the biological function of DevS as an oxygen sensor directly involved in the dormancy/latency of Mtb.

Asunto(s)

RESUMEN

A high resolution mass spectrometry method was developed for the environmental impact monitoring of oil spill dispersants. Previously reported instability of dioctyl sulfosuccinate (DOSS) dispersant tracer was addressed by the new procedure. The method monitors both DOSS and its degradation product, monooctyl sulfosuccinate (MOSS), by liquid chromatography time-of-flight mass spectrometry. The related isomer, 4-(2-ethylhexyl) 2-sulfobutanedioate, was chromatographically resolved from MOSS but was not a product of DOSS degradation. Using this direct injection method (10 µL), the practical lower limit of quantitation was 0.5 nM for each analyte, a concentration equivalent to 0.22 ng mL-1, or 0.30 ng mL-1 including initial dilution factor with acetonitrile. The method was shown applicable to analysis of the dispersants Corexit® EC9500 A, Finasol OSR 52, Slickgone NS, and Slickgone EW for which DOSS is an active ingredient. A marine microcosm study of Corexit EC9500A, together with diluted bitumen (dilbit), at 15 ± 1 °C, provided evidence of the stoichiometric conversion of DOSS to MOSS under conditions reflecting a western Canadian marine environment. The advantage of the developed method is in its ability to extend environmental seawater sample collection time from 4 days for DOSS alone, to 14 days when both DOSS and MOSS are simultaneously analysed and results combined. The collection time is likely extended beyond the 14 day period with cooler temperatures. Preservation of collected seawater samples using sodium hydroxide, converting DOSS into MOSS in situ, was rejected due to stability issues. Addition of disodium ethylenediaminetetraacetic acid did not improve hold times, thus eliminating the theory of cation induced micelle effects causing DOSS loss.

Asunto(s)

RESUMEN

Conscientious objectors are typically defined only by their unwillingness to serve in the armed forces. Desmond Doss participated in World War II as a combat medic and a conscientious objector by providing emergency medicine on active battlefields while refusing to handle a weapon or harm another human being. Born and raised with humility, Doss developed spiritually as a Seventh Day Adventist. Although fixated on the Ten Commandments and "Thou shall not kill," Doss felt a call to serve and voluntarily enlisted in the U.S. Army with aspirations of becoming a combat medic. Throughout his training he was met with physical, spiritual, and political obstacles as his superiors unsuccessfully tried to convince him and eventually to force him out of the military or to take up arms and fight. Doss was granted his request as a combat medic, was not required to handle a weapon or fight, and was deployed with the 307th Infantry Regiment overseas. His heroism on the battlefield saved hundreds of lives and earned him the Medal of Honor. A thorough yet concise examination of Doss' formative years, the obstacles presented by the country he aimed to serve, how he evolved from a conscientious objector to a combat medic worthy of emulation, and his lasting legacy is a necessary reminder of what we risk when courageous people are limited by outdated and potentially unconstitutional policies and perceptions.

Asunto(s)

RESUMEN

The present study investigated oil dispersant toxicity to fish species typical of the cooler regions of Canada, together with less well-documented issues pertaining to oil dispersant monitoring. The oil dispersant toxicity of Corexit EC9500A was assessed for the freshwater fish species rainbow trout and the seawater species coho, chinook, and chum, with a final median lethal concentration (LC50) acute lethality range between 35.3 and 59.8 mg/L. The LC50 range was calculated using confirmed 0-h dispersant concentrations that were justified by fish mortality within the first 24 h of exposure and by variability of the dispersant indicator dioctyl sulfosuccinate (DOSS) used to monitor concentrations at later time points. To investigate DOSS as an oil dispersant indicator in the environment, microcosm systems were prepared containing Corexit EC9500A, Finasol OSR52, Slickgone NS, and Slickgone EW dispersants together with diluted bitumen. The DOSS indicator recovery was found to be stable for up to 13 d at 5 °C, 8 d at 10 °C, but significantly less than 8 d at ≥15 °C. After 3 d at temperatures ≥15 °C, the DOSS indicator recovery became less accurate and was dependent on multiple environmental factors including temperature, microbial activity, and aeration, with potential for loss of solvents and stabilizers. A final assessment determined DOSS to be a discrepant indicator for long-term monitoring of oil dispersant in seawater. Environ Toxicol Chem 2018;37:1309-1319. © 2018 SETAC.

Asunto(s)

RESUMEN

Large-scale use of dispersants to remediate oil spills has raised concerns about their toxicity to marine organisms. Of particular concern is oxidative stress and resulting membrane damage due to exposure to surfactants in dispersant mixtures. We investigated the potential of the dispersant Corexit 9500® and one of its major components, the anionic surfactant dioctyl sodium sulfosuccinate (DOSS), to induce oxidative stress in larval sheepshead minnows after 24 and 96h exposures, at two sublethal concentrations, the lesser being environmentally realistic for each compound. Corexit exposures elicited only minimal antioxidant responses for most antioxidant components tested, with increased glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities observed only after 96h and at the higher exposure concentration. In contrast, DOSS induced statistically significant increases in the levels of reactive oxygen species (ROS), GPx, and lipid peroxidation, as well as depleted reduced glutathione (GSH) levels at both time points and concentrations. These data indicate that short-term and environmentally realistic exposures to DOSS can impact antioxidant response capabilities, raising concern about its use in oil dispersants and other high volume use products where environmental releases are likely.

Asunto(s)

RESUMEN

The utilization of the cationic lipid R-DOTAP as immune cell stimulant (e.g. its stimulating effects on immature dendritic cells) and correspondingly as possible adjuvant for vaccination is well known. Likewise, it is described in literature that solid polymer particles loaded with antigens can be size-tailored in a manner to be suitable for phagocytosis by antigen presenting cells. The effects of DOTAP-microparticle combinations, however, are not well understood. This study aimed therefore to explore the potential of R-DOTAP stabilized microparticles (MP) to act as a carrier platform for antigens e.g. for cancer vaccination. It was investigated whether or not a combination of R-DOTAP and PLGA leads to a boosted adjuvant effect in dendritic cell maturation. For proper comparison, neutral and negatively charged MPs of comparable sizes were developed. Toxicity, uptake, routing and maturation of the MP platform was assessed in-vitro on human immature dendritic cells (iDCs). Interestingly, none of the tested placebo formulations (without antigen) was capable to induce DC maturation when compared to LPS as positive control. This is in contrast to experiments previously reported in literature, where R-DOTAP (e.g. in liposomal form) triggered iDC maturation even without antigen. Possible reasons and further approaches are discussed in the paper.

Asunto(s)