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Although non‐aqueous phase liquids (NAPLs) are typically released to the environment as complex mixtures, most investigations of subsurface remediation focus on single contaminants and ignore the potential effects of co‐constituents on mass recovery and groundwater plume evolution. In this study, we investigate the dissolution and micellar solubilization of binary NAPL mixtures in completely mixed batch reactors and heterogeneous aquifer cells using a commercially‐available nonionic surfactant, Tween® 80. Micellar solubilization of trichloroethene (TCE), tetrachloroethene (PCE), decane, and dodecane measured in batch studies containing binary mixtures of TCE/PCE or decane/dodecane exhibited nonideal behavior that could not be predicted using Raoult's law. For a mixed PCE/decane NAPL, micellar solubilization of PCE was approximately 40% less than predicted, while decane was over 100% greater, which was attributed to expansion of the micelle core. In two aquifer cells containing different size fractions of quartz sand and low‐permeability lenses, the initial NAPL (1:1 TCE:PCE) saturation distributions resulted in "pool" fractions (PFs) of 0.88 and 0.36. During the initial water flood, the greater aqueous solubility of TCE relative to PCE resulted in preferential removal of TCE from the source zone. However, when a 4% (wt) solution of Tween® 80 was introduced, preferential micellar solubilization of PCE relative to TCE resulted in enhanced removal of PCE, with TCE mass discharge reduced from 97% and 90% and PCE mass discharge reduced from 79% and 53%. The observed relationships between mass discharge and mass removal indicating that plume evolution is strongly influenced by the initial NAPL saturation distribution, changes in the mole fraction of NAPL constituents, and regions of high NAPL saturation that persist over time. [ABSTRACT FROM AUTHOR]

Bioremediation treatment (e.g. biostimulation) can decrease groundwater pH with consequences for Dehalococcoides mccartyi (Dhc) reductive dechlorination activity. To explore the pH resilience of Dhc, the Dhc-containing consortium BDI was exposed to pH 5.5 for up to 40 days. Following 8- and 16-day exposure periods to pH 5.5, dechlorination activity and growth recovered when returned to pH 7.2; however, the ability of the culture to dechlorinate vinyl chloride (VC) to ethene was impaired (i.e. decreased rate of VC transformation). Dhc cells exposed to pH 5.5 for 40 days did not recover the ethene-producing phenotype upon transfer to pH 7.2 even after 200 days of incubation. When returned to pH 7.2 conditions after an 8-, a 16- and a 40-day low pH exposure, tceA and vcrA genes showed distinct fold increases, suggesting Dhc strain-specific responses to low pH exposure. Furthermore, a survey of Dhc biomarker genes in groundwater samples revealed the average abundances of Dhc 16S rRNA, tceA and vcrA genes in pH 4.5-6 groundwater were significantly lower (P-value < 0.05) than in pH 6-8.3 groundwater. Overall, the results of the laboratory study and the assessment of field data demonstrate that sustained Dhc activity should not be expected in low pH groundwater, and the duration of low pH exposure affects the ability of Dhc to recover activity at circumneutral pH. [ABSTRACT FROM AUTHOR]

Bioremediation at chlorinated solvent sites often leads to groundwater acidification due to electron donor fermentation and enhanced dechlorination activity. The microbial reductive dechlorination process is robust at circumneutral pH, but activity declines at groundwater pH values below 6.0. Consistent with this observation, the activity of tetrachloroethene (PCE) dechlorinating cultures declined at pH 6.0 and was not sustained in pH 5.5 medium, with one notable exception. Sulfurospirillum multivorans dechlorinated PCE to cis-1,2-dichloroethene (cDCE) in pH 5.5 medium and maintained this activity upon repeated transfers. Microcosms established with soil and aquifer materials from five distinct locations dechlorinated PCE-to-ethene at pH 5.5 and pH 7.2. Dechlorination to ethene was maintained following repeated transfers at pH 7.2, but no ethene was produced at pH 5.5, and only the transfer cultures derived from the Axton Cross Superfund (ACS) microcosms sustained PCE dechlorination to cDCE as a final product. 16S rRNA gene amplicon sequencing of pH 7.2 and pH 5.5 ACS enrichments revealed distinct microbial communities, with the dominant dechlorinator being Dehalococcoides in pH 7.2 and Sulfurospirillum in pH 5.5 cultures. PCE-to-trichloroethene- (TCE-) and PCE-to-cDCE-dechlorinating isolates obtained from the ACS pH 5.5 enrichment shared 98.6%, and 98.5% 16S rRNA gene sequence similarities to Sulfurospirillum multivorans. These findings imply that sustained Dehalococcoides activity cannot be expected in low pH (i.e., = 5.5) groundwater, and organohalide-respiring Sulfurospirillum spp. are key contributors to in situ PCE reductive dechlorination under low pH conditions. [ABSTRACT FROM AUTHOR]

Background: Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. Methods: Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. Results: Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. Conclusions: In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events. [ABSTRACT FROM AUTHOR]

A combination of batch and column experiments evaluated the mass transfer of two candidate partitioning electron donors (PEDs), n-hexanol (nHex) and n-butyl acetate (nBA), for enhanced bioremediation of trichloroethene (TCE)-dense nonaqueous phase liquid (DNAPL). Completely mixed batch reactor experiments yielded equilibrium TCE-DNAPL and water partition coefficients (KNW) for nHex and nBA of 21.7 ± 0.27 and 330.43 ± 6.7, respectively, over a range of initial PED concentrations up to the aqueous solubility limit of ca. 5000 mg/L. First-order liquid-liquid mass transfer rates determined in batch reactors with nBA or nHex concentrations near the aqueous solubility were 0.22 min-1 and 0.11 min-1, respectively. Liquid-liquid mass transfer under dynamic flow conditions was assessed in one-dimensional (1-D) abiotic columns packed with Federal Fine Ottawa sand containing a uniform distribution of residual TCE-DNAPL. Following pulse injection of PED solutions at pore-water velocities (vp) ranging from 1.2 to 6.0 m/day, effluent concentration measurements demonstrated that both nHex and nBA partitioned strongly into residual TCE-DNAPL with maximum effluent levels not exceeding 35% and 7%, respectively, of the applied concentrations of 4000 to 5000 mg/L. PEDs persisted at effluent concentrations above 5 mg/L for up to 16 and 80 pore volumes for nHex and nBA, respectively. Mathematical simulations yielded KNW values ranging from 44.7 to 48.2 and 247 to 291 and liquid-liquid mass transfer rates of 0.01 to 0.03 min-1 and 0.001 to 0.006 min-1 for nHex and nBA, respectively. The observed TCE-DNAPL and water mass transfer behavior suggests that a single PED injection can persist in a treated source zone for prolonged time periods, thereby reducing the need for, or frequency of, repeated electron donor injections to support bacteria that derive reducing equivalents for TCE reductive dechlorination from PED fermentation. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is characterized by the selective demise of dopaminergic (DA) neurons in the substantial nigra pars compacta. Dysregulation of transcriptional factor myocyte enhancer factor 2D (MEF2D) has been implicated in the pathogenic process in in vivo and in vitro models of PD. Here, we identified a small molecule bis(3)-cognitin (B3C) as a potent activator of MEF2D.We showed that B3C attenuated the toxic effects of neurotoxin 1-methyl-4-phenylpyridinium (MPP+) by activating MEF2D via multiple mechanisms. B3C significantly reduced MPP+-induced oxidative stress and potentiated Akt to down-regulate the activity of MEF2 inhibitor glycogen synthase kinase 3β (GSK3β) in a DA neuronal cell line SN4741. Furthermore, B3C effectively rescued MEF2D from MPP+-induced decline in both nucleic and mitochondrial compartments. B3C offered SN4741 cells potent protection against MPP+-induced apoptosis via MEF2D. Interestingly, B3C also protected SN4741 cells from wild type or mutant A53T α-synuclein-induced cytotoxicity. Using the in vivo PD model of C57BL/6 mice treated with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine hydrochloride (MPTP), we showed that B3C maintained redox homeostasis, promoted Akt function activity, and restored MEF2D level in midbrain neurons. Moreover, B3C greatly prevented the loss of tyrosine hydroxylase signal in substantial nigra pars compacta DA neurons and ameliorated behavioral impairments in mice treated with MPTP. Collectedly, our studies identified B3C as a potent neuroprotective agent whose effectiveness relies on its ability to effectively up-regulate MEF2D in DA neurons against toxic stress in models of PD in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The environmental fate of per- and polyfluoroalkyl substances (PFAS) in aqueous film-forming foams (AFFFs), especially those synthesized by electrochemical fluorination (ECF) processes, remains largely unknown. This study evaluated the transformation of AFFF-derived ECF-based precursors in aerobic soil microcosms amended with a historically used AFFF formulation (3M Light Water TM ). Fifteen classes of PFAS, including AFFF components and transformation products, were identified or tentatively identified by suspect screening/nontargeted analysis (SSA/NTA) throughout a 308-day incubation. This study demonstrates that AFFF-derived ECF-based precursors serve as sources of perfluoroalkane sulfonamides (FASAs) and perfluoroalkyl acids (PFAAs), which are commonly detected at AFFF-impacted sites. Temporal sampling provided evidence for biotransformation of multiple precursors including tri- or dimethyl ammonio propyl perfluoroalkane sulfonamides. Additionally, the environmental stability (i.e., resistance to transformation) of ECF-based precursors was found to depend upon structural characteristics, including perfluoroalkyl chain length, presence of sulfonamide or carboxamide groups, and functional groups (e.g., a branch of carboxyalkyl group) attached to the nitrogen atoms. These findings provide insights into the transformation pathways of AFFF-derived PFAS and other structurally similar ECF-based PFAS, which will support the management and remediation of PFAS contamination at legacy AFFF-impacted sites.