Effects of temperature on nitrifying membrane-aerated biofilms: An experimental and modeling study.

Temperature is known to have an important effect on the morphology and removal fluxes of conventional, co-diffusional biofilms. However, much less is known about the effects of temperature on membrane-aerated biofilm reactors (MABRs). Experiments and modeling were used to determine the effects of temperature on the removal fluxes, biofilm thickness and morphology, and biofilm microbial community structure of nitrifying MABRs. Steady state tests were carried out at 10 °C and 30 °C. MABRs grown at 30 °C had higher ammonium removal fluxes (5.5 ± 0.9 g-N/m2/day at 20 mgN/L) than those grown at 10 °C (3.4 ± 0.2 g-N/m2/day at 20 mgN/L). The 30 °C biofilms were thinner and rougher, with a lower protein to polysaccharides ratio (PN/PS) in their extracellular polymeric substance (EPS) matrix and greater amounts of biofilm detachment. Based on fluorescent in-situ hybridization (FISH), there was a higher relative abundance of nitrifying bacteria at 30 °C than at 10 °C, and the ratio of AOB to total nitrifiers (AOB + NOB) was higher at 30 °C (95.1 ± 2.3%) than at 10 °C (77.2 ± 8.6 %). Anammox bacteria were more abundant at 30 °C (16.6 ± 3.7 %) than at 10 °C (6.5 ± 2.4 %). Modeling suggested that higher temperatures increase ammonium oxidation fluxes when the biofilm is limited by ammonium. However, fluxes decrease when oxygen becomes limited, i.e., when the bulk ammonium concentrations are high, due to decreased oxygen solubility. Consistent with the experimental results, the model predicted that the percentage of AOB to total nitrifiers at 30 °C was higher than at 10 °C. To investigate the effects of temperature on biofilm diffusivity and O2 solubility, without longer-term changes in the microbial community, MABR biofilms were grown to steady state at 20 °C, then the temperature changed to 10 °C or 30 °C overnight. Higher ammonium oxidation fluxes were obtained at higher temperatures: 1.91 ± 0.24 g-N/m2/day at 10 °C and 3.19 ± 0.40 g-N/m2/day at 30 °C. Overall, this work provides detailed insights into the effect of temperature on nitrifying MABRs, which can be used to better understand MABR behavior and manage MABR reactors.

Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke.

Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.

Unique stratification of biofilm density in heterotrophic membrane-aerated biofilms: An experimental and modeling study.

We consistently find a band of high cell density develop within heterotrophic membrane-aerated biofilms. This study reports and attempts to explain this unique behavior. Biofilm density affects volumetric reaction rates, biofilm growth rates, substrate diffusion, and mechanical behavior. Yet the mechanisms and dynamics of biofilm density development are poorly understood. In this study, a membrane-aerated biofilm, where O2 was supplied from the base of the biofilm and acetate from the bulk liquid, was used to explore spatial and temporal patterns of density development. Biofilm density was assessed by optical coherence tomography. After inoculation, the biofilm quickly increased in thickness, with a low density throughout. However, as the biofilm reached a stable thickness of around 1000 µm, a high-density layer developed in the biofilm interior. The layer slowly expanded over time. Oxygen microprofiles in the biofilm showed this layer coincided with the most metabolically active zone, resulting from counter-diffusing O2 and acetate. The formation of this dense layer appeared to be related to changes in growth rates. Initially, high growth rates throughout the biofilm presumably led to fast-growing, low-density biofilms. As the biofilm became thicker, and as substrates became limiting in the biofilm interior, growth rates decreased, resulting in new growth at a higher density. A 1-D mathematical model with variable biofilm density was developed by linking the rates of extracellular polymeric substances (EPS) production to the growth rate. The model captured the initial fast growth at a low density, followed by a slower, substrate-limited growth in the biofilm interior, producing a dense band within the biofilm. Together, these results suggest that low growth rates can lead to high-density zones within the interior of counter-diffusional biofilms. These findings should also be relevant to conventional, co-diffusional biofilms, although differences in density may be less obvious.

Unique biofilm structure and mass transfer mechanisms in the foam aerated biofilm reactor (FABR).

The foam-aerated biofilm reactor (FABR) is a novel biofilm process that can simultaneously remove carbon and nitrogen from wastewater. A porous polyurethane foam sheet forms an interface between wastewater and aerated water, making it a counter-diffusional biofilm process similar to the membrane-aerated biofilm reactor (MABR). However, it is not clear how biofilm develops the foam interior, and how this impacts mass transfer and performance. This research explored biofilm development within the foam sheet and determined whether advective transport within the sheet played a significant role. Foam sheets with 2-, 4.5- and 9-mm thicknesses were explored. Oxygen, nitrate, nitrite and ammonia profiles in the sheet were measured using microsensors, and biofilm imaging studies were carried out using optical coherence tomography (OCT). On the foam's aerated side, a dense nitrifying biofilm formed. Beyond the aerobic zone, much less biomass was observed, with a high porosity foam-biofilm layer. The higher effective diffusivity within the foam for the 4- and 9-mm sheets suggested advective transport within the foam channel structures. Using an effective diffusivity factor in conventional 1-D biofilm models reproduced the measured substrate concentration profiles within the foam. Four different practical conditions were modelled. The maximum TN removal efficiency was about 70% and a nitrogen removal flux of 1.25 gN.m-2.d-1. We conclude that mass transfer resistance occurred primarily in the dense, nitrifying layer near the aerated side. The rest of the foam sheet was porous, allowing the advective mass transfer.

Association between LAG3/CD4 Genes Variants and Risk for Multiple Sclerosis.

Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population.

Effect of membrane type on the behavior of nitrifying membrane aerated biofilms: silicone membranes vs. micromembrane cords.

There is increasing interest in membrane-aerated biofilm reactors (MABRs), due to their energy efficiency and ability to intensify wastewater treatment. While MABR membranes play a key role, supporting biofilms and transferring O2, little research has addressed how membrane types impact MABR performance. This research compared two types of membranes used in commercial MABRs: a silicone hollow-fibre membrane and a 'micromembrane cord,' consisting of an inert cord surrounded by fine proprietary polymeric membranes. We used single-membrane MABRs to determine the oxygen mass transfer coefficient, Km, and explore biofilm development. The silicone membrane had a measured Km of 2.6 m/d, and the micromembrane cord had an apparent Km of 1 m/d. Pure MABR bundles (only biofilm) were operated with synthetic wastewater, and hybrid MABRs (suspended biomass and biofilm) with real wastewater, to explore behaviour for a wide range of conditions. The maximum ammonium oxidation fluxes with synthetic wastewater were 7.8 gN/m2d for the silicone membrane and 4.3 gN/m2d for the micromembrane cord. However, at bulk NH4+ concentrations below 5 mgN/L, the ammonium oxidation fluxes were similar. A previously published MABR model effectively captured the behaviour of each membrane. Nitrification fluxes with real wastewater were lower than synthetic wastewater, likely because of the presence of chemical oxygen demand (COD). Although the ammonium oxidation fluxes were higher for the silicone membranes for a given air supply pressure, the fluxes for the micromembrane cord could be increased using higher intramembrane air pressures. Overall, this research helped understand the impact of membrane types on nitrification fluxes.

Assessing Intermediate Formation and Electron Competition during Thiosulfate-Driven Denitrification: An Experimental and Modeling Study.

There is increasing interest in thiosulfate-driven denitrification for low C/N wastewater treatment, but the denitrification performance varies with the thiosulfate oxidation pathways. Models have been developed to predict the products of denitrification, but few consider thiosulfate reduction to elemental sulfur (S0), an undesirable reaction that can intensify electron competition with denitrifying enzymes. In this study, the model using indirect coupling of electrons (ICE) was developed to predict S0 formation and electron competition during thiosulfate-driven denitrification. Kinetic data were obtained from sulfur-oxidizing bacteria (SOB) dominated by the branched pathway and were used to calibrate and validate the model. Electron competition was investigated under different operating conditions. Modeling results reveal that electrons produced in the first step of thiosulfate oxidation typically prioritize thiosulfate reduction, then nitrate reduction, and finally nitrite reduction. However, the electron consumption rate for S0 formation decreases sharply with the decline of thiosulfate concentration. Thus, a continuous feeding strategy was effective in alleviating the competition between thiosulfate reduction and denitrifying enzymes. Electron competition leads to nitrite accumulation, which could be a reliable substrate for anammox. The model was further evaluated with anammox integration. Results suggested that the branched pathway and continuous supply of thiosulfate are favorable to create a symbiotic relationship between SOB and anammox.

Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles.

Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18 h, much longer than the commercial soluble drug dexamethasone phosphate (DSP). Biodistribution studies showed lower DXM concentrations in the liver, kidneys, and lungs when DXP-NPs were administered as compared with the soluble drug. Histology analysis revealed an improvement in the knee structure and reduction of cell infiltration in animals treated with the encapsulated DXP compared with the soluble DSP or non-treated animals. In summary, the encapsulation of a lipidic prodrug of dexamethasone into PLGA-PEG NPs appears as a promising strategy to improve the pharmacological profile and reduce joint inflammation in a murine model of rheumatoid arthritis.

Unraveling encapsulated growth of Nitrosomonas europaea in alginate: An experimental and modeling study.

Encapsulation is a promising technology to retain and protect autotrophs for biological nitrogen removal. One-dimensional biofilm models have been used to describe encapsulated systems; they do not, however, incorporate chemical sorption to the encapsulant nor do they adequately describe cell growth and distribution within the encapsulant. In this research we developed a new model to describe encapsulated growth and activity of Nitrosomonas europaea, incorporating ammonium sorption to the alginate encapsulant. Batch and continuous flow reactors were used to verify the simulation results. Quantitative PCR and cross-section fluorescence in situ hybridization were used to analyze the growth and spatial distribution of the encapsulated cells within alginate. Preferential growth of Nitrosomonas near the surface of the encapsulant was predicted by the model and confirmed by experiments. The modeling and experimental results also suggested that smaller encapsulants with a larger surface area to volume ratio would improve ammonia oxidation. Excessive aeration caused the breakage of the encapsulant, resulting in unpredicted microbial release and washout. Overall, our modeling approach is flexible and can be used to engineer and optimize encapsulated systems for enhanced biological nitrogen removal. Similar modeling approaches can be used to incorporate sorption of additional species within an encapsulant, additional nitrogen-converting microorganisms, and the use of other encapsulation materials.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

Stroke Acute Management and Outcomes During the COVID-19 Outbreak: A Cohort Study From the Madrid Stroke Network.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

A computational model for the catalytic hydrogel membrane reactor.

The catalytic hydrogel membrane reactor (CHMR) is a promising new technology for hydrogenation of aqueous contaminants in drinking water. It offers numerous benefits over conventional three-phase reactors, including immobilization of nano-catalysts, high reactivity, and control over the hydrogen (H2) supply concentration. In this study, a computational model of the CHMR was developed using AQUASIM and calibrated with 32 experimental datasets for a nitrite (NO2-)-reducing CHMR using palladium (Pd) nano-catalysts (~4.6 nm). The model was then used to identify key factors impacting the behavior of the CHMR, including hydrogel catalyst density, H2 supply pressure, influent and bulk NO2- concentrations, and hydrogel thickness. Based on the model calibration, the reaction rate constants for the NO2- steady-state adsorption Hinshelwood reaction equation, k1 and k2, were 0.0039 m3 mole-Pd-1 s-1 and 0.027 (mole-H2 m3)1/2 mole-Pd-1 s-1, respectively. The reactant flux, which is the overall NO2- removal rate for the CHMR, is affected by the NO2- reduction rate at each catalyst site, which is in turn controlled by the available NO2- and H2 concentrations that are regulated by their mass transport behavior. Reactant transport in the CHMR is counter-diffusional. So for thick hydrogels, the concurrent concentrations of NO2- and H2 are limiting in the middle region along the x-y plane of the hydrogel, which results in a low overall NO2- removal rate (i.e., flux). Thinner hydrogels provide higher concurrent reactant concentrations throughout the hydrogel, resulting in higher fluxes. However, if the hydrogel is too thin, the flux becomes limited by the amount of Pd that can be loaded, and unused H2 can diffuse into the bulk and promote biofilm growth. The hydrogel thickness that maximized the NO2- flux ranged between 30 and 150 µm for the conditions tested. The computational model is the first to describe CHMR behavior, and it is an important tool for the further development of the CHMR. It also can be adapted to assess CHMR behavior for other contaminants or catalysts or used for other types of interfacial catalytic membrane reactors.

New insight into CO2-mediated denitrification process in H2-based membrane biofilm reactor: An experimental and modeling study.

The H2-based membrane biofilm reactor (H2-MBfR) is an emerging technology for removal of nitrate (NO3-) in water supplies. In this research, a lab-scale H2-MBfR equipped with a separated CO2 providing system and a microsensor measuring unit was developed for NO3- removal from synthetic groundwater. Experimental results show that efficient NO3- reduction with a flux of 1.46 g/(m2⋅d) was achieved at the optimal operating conditions of hydraulic retention time (HRT) 80 min, influent NO3- concentration 20 mg N/L, H2 pressure 5 psig and CO2 addition 50 mg/L. Given the complex counter-diffusion of substrates in the H2-MBfR, mathematical modeling is a key tool to both understand its behavior and optimize its performance. A sophisticated model was successfully established, calibrated and validated via comparing the measured and simulated system performance and/or substrate gradients within biofilm. Model results indicate that i) even under the optimal operating conditions, denitrifying bacteria (DNB) in the interior and exterior of biofilm suffered low growth rate, attributed to CO2 and H2 limitation, respectively; ii) appropriate operating parameters are essential to maintaining high activity of DNB in the biofilm; iii) CO2 concentration was the decisive factor which matters its dominant role in mediating hydrogenotrophic denitrification process; iv) the predicted optimum biofilm thickness was 650 µm that can maximize the denitrification flux and prevent loss of H2.

Endothelial nitric oxide synthase (NOS3) rs2070744 polymorphism and risk for multiple sclerosis.

The possible role of oxidative stress and nitric oxide (NO) in the pathogenesis of multiple sclerosis (MS) has been suggested by several neuropathological, biochemical, and experimental data. Because the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) showed association with the risk for MS in Iranians, we attempted to replicate the possible association between this SNP and the risk for MS in the Caucasian Spanish population. The frequencies of NOS3rs2070744 genotypes and allelic variants in 300 patients diagnosed with MS and 380 healthy controls were assessed with a TaqMan-based qPCR assay. The possible influence of the genotype frequency on age at onset of MS, the severity of MS, clinical evolutive subtypes of MS, and HLA-DRB1*1501 genotype were also analyzed. The frequencies of rs2070744 genotypes and allelic variants were not associated with the risk of developing MS and were not influenced by gender, age at onset and severity of MS, the clinical subtype of MS or the HLA-DRB1*1501 genotype. This study found a lack of association between NOS3 rs2070744 SNP and the risk for MS in Caucasian Spanish people.

Catalytic Hydrogel Membrane Reactor for Treatment of Aqueous Contaminants.

Heterogeneous hydrogenation catalysis is a promising approach for treating oxidized contaminants in drinking water, but scale-up has been limited by the challenge of immobilization of the catalyst while maintaining efficient mass transport and reaction kinetics. We describe a new process that addresses this issue: the catalytic hydrogel membrane (CHM) reactor. The CHM consists of a gas-permeable hollow-fiber membrane coated with an alginate-based hydrogel containing catalyst nanoparticles. The CHM benefits from counter-diffusional transport within the hydrogel, where H2 diffuses from the interior of the membrane and contaminant species (e.g., NO2-, O2) diffuse from the bulk aqueous solution. The reduction of O2 and NO2- were investigated using CHMs with varying palladium catalyst densities, and mass transport of reactive species in the catalytic hydrogel was characterized using microsensors. The thickness of the "reactive zone" within the hydrogel affected the reaction rate and byproduct selectivity, and it was dependent on catalyst density. In a continuously mixed flow reactor test using groundwater, the CHM activity was stable for a 3 day period. Outcomes of this study illustrate the potential of the CHM as a scalable process in the treatment of aqueous contaminants.

Mechanical thrombectomy in patients with medical contraindications for intravenous thrombolysis: a prospective observational study.

BACKGROUND AND PURPOSE: The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. METHODS: A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5 hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, modified Rankin Scale (mRS) score and mortality at 90 days. RESULTS: Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0-2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. CONCLUSIONS: MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. TRIAL REGISTRATION NUMBER: NCT02164357; Results.

Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Multiple Sclerosis.

Several neurochemical, neuropathological, and experimental data suggest a possible role of oxidative stress in the ethiopathogenesis of multiple sclerosis(MS). Heme-oxygenases(HMOX) are an important defensive mechanism against oxidative stress, and HMOX1 is overexpressed in the brain and spinal cord of MS patients and in experimental autoimmune encephalomyelitis(EAE). We analyzed whether common polymorphisms affecting the HMOX1 and HMOX2 genes are related with the risk to develop MS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations(CNVs) of these genes in 292 subjects MS and 533 healthy controls, using TaqMan assays. The frequencies of HMOX2 rs1051308AA genotype and HMOX2 rs1051308A and HMOX1 rs2071746A alleles were higher in MS patients than in controls, although only that of the SNP HMOX2 rs1051308 in men remained as significant after correction for multiple comparisons. None of the studied polymorphisms was related to the age at disease onset or with the MS phenotype. The present study suggests a weak association between HMOX2 rs1051308 polymorphism and the risk to develop MS in Spanish Caucasian men and a trend towards association between the HMOX1 rs2071746A and MS risk.

Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke.

INTRODUCTION: Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. METHODS: Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, time-lapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). RESULTS: Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT + MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3-0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5-1.2). A score ≤5 in CTA-SI-ASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). CONCLUSIONS: CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies.

Controlled Release, Intestinal Transport, and Oral Bioavailablity of Paclitaxel Can be Considerably Increased Using Suitably Tailored Pegylated Poly(Anhydride) Nanoparticles.

The aim of the work was to evaluate in vitro and in vivo the effect of the addition of poly(ethylene glycol) (PEG) to paclitaxel (PTX)-cyclodextrin poly(anhydride) nanoparticles. For this, PTX in poly(anhydride) nanoparticles complexed with cyclodextrins (either 2-hydroxypropyl-ß-cyclodextrin or ß-cyclodextrin) and combined with PEG 2000 were prepared by the solvent displacement method. Intestinal permeability in vitro and in vivo pharmacokinetic studies in C57BL/6J mice were performed. Nanoparticle formulations containing PTX increased its apparent permeability through rat intestine in vitro in the Ussing chambers, enhancing its permeability 10-15 times compared with commercial Taxol®. In addition, in pharmacokinetic studies, drug plasma levels were observed for at least 24 h leading to a relative oral bioavailability between 60% and 80% for PTX complexed with cyclodextrin and loaded in pegylated poly(anhydride) nanoparticles after oral gavage. In all, PTX-cyclodextrin complexes encapsulated in pegylated nanoparticles managed to promote the intestinal uptake of the drug displaying sustained plasma levels after oral administration to laboratory animals with a more prolonged plasma profile compared with the formulation with no PEG at all. Therefore, pegylated poly(anhydride) nanoparticles represent a promising carrier for the oral delivery of PTX.