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The precise identification of predominant toxic disinfection byproducts (DBPs) from disinfected water is a longstanding challenge. We propose a new acellular analytical strategy, the 'Thiol Reactome', to identify thiol-reactive DBPs by employing a thiol probe and nontargeted mass spectrometry (MS) analysis. Disinfected/oxidized water samples had reduced cellular oxidative stress responses of 46 ± 23% in Nrf2 reporter cells when preincubated with glutathione (GSH). This supports thiol-reactive DBPs as the predominant drivers of oxidative stress. This method was benchmarked using seven classes of DBPs including haloacetonitriles, which preferentially reacted with GSH via substitution or addition depending on the number of halogens present. The method was then applied to chemically disinfected/oxidized waters, and 181 tentative DBP-GSH reaction products were detected. The formulas of 24 high abundance DBP-GSH adducts were predicted, among which nitrogenous-DBPs (11) and unsaturated carbonyls (4) were the predominant compound classes. Two major unsaturated carbonyl-GSH adducts, GSH-acrolein and GSH-acrylic acid, were confirmed by their authentic standards. These two adducts were unexpectedly formed from larger native DBPs when reacting with GSH. This study demonstrated the "Thiol Reactome" as an effective acellular assay to precisely identify and broadly capture toxic DBPs from water mixtures.
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Desinfectantes , Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Desinfección , Agua Potable/análisis , Agua Potable/química , Desinfectantes/análisis , Desinfectantes/química , Compuestos de Sulfhidrilo , Purificación del Agua/métodos , Contaminantes Químicos del Agua/análisis , HalogenaciónRESUMEN
When the COVID-19 pandemic hit and international travel was halted, nursing faculty were challenged to transform the in-person global health clinical experience with travel to a new virtual format. The virtual experience would need to meet the learning objectives and provide a global health perspective. This article describes the process of transforming the in-person clinical experience to a virtual format to provide a rich global learning opportunity for the students without travel to the host country. Virtual global health experiences can successfully help students understand the health of populations with a global perspective.
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AIM: Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first-in-human study, we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the SARM GSK2881078. METHODS: In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching-placebo). In Part B, repeat-dose cohorts in men (n = 65) were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in women (n = 24) they were 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days for other doses). RESULTS: PK analysis showed dose-proportional increases in exposure and a long >100-h half-life. No significant effects on vital signs, electrocardiograms, cardiac telemetry or standard clinical laboratory studies were observed. A dose-response effect was observed on lowering both high-density lipoprotein and sex hormone-binding globulin. In females at 0.35 mg, differences from placebo were -0.518 (95% confidence interval: -0.703, -0.334) mmol l-1 and -39.1 (-48.5, -29.7) nmol l-1 , respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug-related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow-up. A serious AE occurred in a subject on placebo. CONCLUSIONS: These data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.
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Anabolizantes/farmacología , Indoles/farmacología , Fuerza Muscular/efectos de los fármacos , Receptores Androgénicos/metabolismo , Administración Oral , Adulto , Anciano , Anabolizantes/efectos adversos , Anabolizantes/farmacocinética , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electrocardiografía , Femenino , Semivida , Voluntarios Sanos , Corazón/efectos de los fármacos , Humanos , Indoles/efectos adversos , Indoles/farmacocinética , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Placebos , Posmenopausia , Factores Sexuales , Globulina de Unión a Hormona Sexual/análisis , Adulto JovenRESUMEN
GSK-1614235 and KGA-2727 are potent, selective inhibitors of the SGLT1 sodium-dependent glucose transporter. Nonclinical (KGA-2727) and clinical (GSK-1614235) trials assessed translation of SGLT1 inhibitor effects from rats to normal human physiology. In rats, KGA-2727 (0.1 mg/kg) or vehicle was given before oral administration of 3-O-methyl-α-d-glucopyranose (3-O-methylglucose, 3-OMG) containing 3-[3H]OMG tracer. Tracer absorption and distribution were assessed from plasma, urine, and fecal samples. SGLT1 inhibition reduced urine 3-OMG recovery and increased fecal excretion. SGLT1 inhibitor effects on plasma glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were also measured during a standard meal. Incremental glucose, insulin, and GIP concentrations were decreased, indicating downregulation of ß-cell and K cell secretion. Minimal effects were observed in the secretion of the L cell product, GLP-1. With the use of a three-way, crossover design, 12 healthy human subjects received placebo or 20 mg GSK-1614235 immediately before or after a meal. Five minutes into the meal, 3-OMG was ingested. Postmeal dosing had little impact, yet premeal dosing delayed and reduced 3-OMG absorption, with an AUC0-10 of 231±31 vs. 446±31 µg·h(-1)·ml(-1), for placebo. Recovery of tracer in urine was 1.2±0.7 g for premeal dosing and 2.2±0.1 g for placebo. Incremental concentrations of insulin, C-peptide, and GIP were reduced for 2 h with premeal GSK-1614235. Total GLP-1 concentrations were significantly increased, and a trend for increased peptide YY (PYY) was noted. SGLT1 inhibitors block intestinal glucose absorption and reduce GIP secretion in rats and humans, suggesting SGLT1 glucose transport is critical for GIP release. Conversely, GLP-1 and PYY secretion are enhanced by SGLT1 inhibition in humans.
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Glucósidos/farmacocinética , Absorción Intestinal , Pirazoles/farmacocinética , Transportador 1 de Sodio-Glucosa/antagonistas & inhibidores , 3-O-Metilglucosa/farmacocinética , Administración Oral , Adulto , Animales , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón/sangre , Glucosa/análisis , Humanos , Insulina/sangre , Absorción Intestinal/efectos de los fármacos , Absorción Intestinal/fisiología , Mucosa Intestinal/metabolismo , Intestino Delgado/fisiología , Masculino , Persona de Mediana Edad , Ratas , Resultado del TratamientoRESUMEN
Background: Studies of hyperbaric oxygen therapy (HBOT) treatment of mild traumatic brain injury persistent postconcussion syndrome in military and civilian subjects have shown simultaneous improvement in posttraumatic stress disorder (PTSD) or PTSD symptoms, suggesting that HBOT may be an effective treatment for PTSD. This is a systematic review and dosage analysis of HBOT treatment of patients with PTSD symptoms. Methods: PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from September 18 to November 23, 2023, for all adult clinical studies published in English on HBOT and PTSD. Randomized trials and studies with symptomatic outcomes were selected for final analysis and analyzed according to the dose of oxygen and barometric pressure on symptom outcomes. Outcome assessment was for statistically significant change and Reliable Change or Clinically Significant Change according to the National Center for PTSD Guidelines. Methodologic quality and bias were determined with the PEDro Scale. Results: Eight studies were included, all with < 75 subjects/study, total 393 subjects: seven randomized trials and one imaging case-controlled study. Six studies were on military subjects, one on civilian and military subjects, and one on civilians. Subjects were 3-450 months post trauma. Statistically significant symptomatic improvements, as well as Reliable Change or Clinically Significant changes, were achieved for patients treated with 40-60 HBOTS over a wide range of pressures from 1.3 to 2.0 ATA. There was a linear dose-response relationship for increased symptomatic improvement with increasing cumulative oxygen dose from 1002 to 11,400 atmosphere-minutes of oxygen. The greater symptomatic response was accompanied by a greater and severe reversible exacerbation of emotional symptoms at the highest oxygen doses in 30-39% of subjects. Other side effects were transient and minor. In three studies the symptomatic improvements were associated with functional and anatomic brain imaging changes. All 7 randomized trials were found to be of good-highest quality by PEDro scale scoring. Discussion: In multiple randomized and randomized controlled clinical trials HBOT demonstrated statistically significant symptomatic improvements, Reliable Changes, or Clinically Significant Changes in patients with PTSD symptoms or PTSD over a wide range of pressure and oxygen doses. The highest doses were associated with a severe reversible exacerbation of emotional symptoms in 30-39% of subjects. Symptomatic improvements were supported by correlative functional and microstructural imaging changes in PTSD-affected brain regions. The imaging findings and hyperbaric oxygen therapy effects indicate that PTSD can no longer be considered strictly a psychiatric disease.
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Microplastics that adsorb various toxic contaminants in water may be transported into cells and organs, possibly posing toxicological risks in the aquatic environment. Disinfection byproducts (DBPs), which are ubiquitous in chlorinated drinking water and wastewater, may have some potential to sorb onto microplastics (MPs) through hydrophobic or electrostatic interactions. However, DBP adsorption on microplastics has not yet been closely examined. This work investigated the adsorption behavior of trihalomethanes (THMs)-a regulated and ubiquitous DBP class in chlorinated water-onto virgin and weathered polyvinyl chloride (PVC) microplastics, the most widely used plastic material in drinking water distribution and sewer systems. A comparative analysis of kinetic and isotherm test results indicated that the adsorption mechanisms mainly involved hydrophobic interactions from a combination of weak and strong physisorption behavior and possibly chemisorption. The adsorption coefficients from all the models examined suggested that the adsorption of THMs, and perhaps chemically similar DBPs, onto virgin PVC microplastics can be 10-20 µg g-1. However, the weathered PVC microplastics contained more polar functional groups, which led to a decreased hydrophobicity and reduced THM adsorption capacity by approximately 10%. These findings offer novel insights into the possible adsorption characteristics of disinfection byproducts (DBPs) onto microplastics and will assist in targeting more toxic DBPs for future investigations.
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Knowledge of the speciation of chlorine and chloramines in reverse osmosis (RO) permeate is needed to estimate the performance (i.e., pollutant log reduction) of subsequent UV/chlorine advanced oxidation processes (AOPs). To accurately predict the speciation, a previously reported breakpoint chlorination kinetic model was experimentally validated for pH 5.5 and reaction times < 3 min and used to predict the kinetics of breakpoint chlorination in RO permeate. The predictions showed that eliminating chloramines by adding chlorine at a dose beyond the chlorine-to-nitrogen (Cl/N) breakpoint ratio is not practical due to the high breakpoint Cl/N ratio for RO permeate (â¼3.0 molar ratio) and an estimated > 40 min reaction time. The conversion from monochloramine (NH2Cl) to dichloramine (NHCl2) is the major process involved, and either or both free chlorine and chloramines may be the major species present, depending on the Cl/N ratio. Model simulations showed that increasing the oxidant dose may not always enhance the performance of UV/chlor(am)ine in RO permeate, due to the need for a low free chlorine dose for optimal â¢OH exposure in RO permeate. Further UV/AOPs modelling showed that it is important to control the NH2Cl concentration to improve the UV/AOP performance in RO permeate, which may be achieved by extending the reaction time after chlorine is added or increasing the applied Cl/N ratio (e.g., increasing chlorine dose). However, these measures only enhance the pollutant percentage removal by about 5 % under the conditions modelled. A simulation tool was developed and is provided to predict the speciation of chlor(am)ine in RO permeate.
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Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Cloraminas , Rayos Ultravioleta , Oxidación-Reducción , Nitrógeno , ÓsmosisRESUMEN
UV/Cl and UV/H2O2 are advanced oxidation processes (AOPs) used for drinking water treatment and water reuse. This work explored the hypothesis that UV/Cl becomes more competitive to UV/H2O2 at neutral-to-high pH as the concentration of total organic carbon (TOC) increases. Lab experiments and kinetic modelling were used to compare initial pseudo first-order contaminant decay rate coefficients between the AOPs at various pH and TOC conditions. The relative effect of increasing TOC concentrations on UV/Cl vs. UV/H2O2 depended on the pH, contaminant, and organic matter reactivity towards radicals. For example, while the reaction rate coefficients during both AOPs generally decreased with increasing TOC, the UV/Cl reaction rate coefficients for the solely â¢OH-reactive sucralose decreased 41-138% less than the UV/H2O2 coefficients as the TOC concentration was increased from 0 to 5 mg-C L-1. However, UV/Cl was more affected than UV/H2O2 when targeting caffeine (a contaminant reactive to chlorine radicals). The data were used to define TOC-pH conditions for which either AOP would be more energy-efficient, under a set of standard conditions. The results suggest that UV/Cl may be competitive to UV/H2O2 under a wider range of treatment scenarios than has been conventionally thought based on tests in pure water.
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Daprodustat, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase enzyme inhibitor, has recently completed phase 3 clinical development for treating anemia of chronic kidney disease. Part A of this 2-part, randomized, double-blind, single-dose, cross-over study (NCT04640311) compared pharmacokinetic properties of a single oral dose of daprodustat 4 mg tablets manufactured via twin-screw wet granulation (process 1) to 2 sets of 4 mg tablets manufactured via high-shear wet granulation (process 2), to assess the impact of different dissolution profiles on pharmacokinetics. Part B assessed the bioequivalence of daprodustat tablets manufactured via process 1 with tablets manufactured via process 2 at 5 different dose strengths (1, 2, 4, 6, and 8 mg). In part A, mean plasma concentrations of daprodustat were comparable over a 24-hour period despite differences in manufacturing processes and dissolution profiles. In part B, the 90% confidence intervals of the ratios of the least squared means for area under the concentration-time curve and maximum observed plasma concentration fell within the 0.8-1.25 bioequivalence range for all doses, except for maximum observed plasma concentration at 8 mg. A prespecified sensitivity analysis jointly assessing all doses showed bioequivalence for all doses tested. No new safety concerns for daprodustat were identified.
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Equivalencia Terapéutica , Humanos , Estudios Cruzados , Solubilidad , ComprimidosRESUMEN
Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor in development for treatment of anemia of chronic kidney disease. We evaluated the role of hepatic impairment on daprodustat pharmacokinetics, pharmacodynamics, and tolerability. Participants with mild (Child-Pugh Class A, score 5-6) and moderate (Child-Pugh Class B, score 7-9) hepatic impairment and matched healthy controls were administered single 6-mg doses of daprodustat. Exposure parameters were determined for daprodustat and its six metabolites. Comparisons resulted in 1.5- and 2.0-fold higher daprodustat Cmax and area under the curve (AUC) exposures in participants with mild and moderate hepatic impairment, respectively, versus controls; Cmax in mild hepatic impairment was comparable to controls. Similarly, aligned with parent drug, unbound daprodustat Cmax and AUC exposures increased 1.6- to 2.3-fold in hepatic-impaired participants versus controls, and metabolite exposures were 1.2- to 2.0-fold higher in participants with hepatic impairment. Erythropoeitin (EPO) baseline-corrected AUC exposures were between 0.3-fold lower and 2.2-fold higher in matched controls versus hepatic-impaired participants. No serious or study drug-related adverse events were reported. Daprodustat exposure was increased in participants with moderate and mild hepatic impairment compared with matched controls; however, no meaningful differences in EPO were observed and no new safety concerns were identified (ClinicalTrials.gov: NCT03223337).
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Hepatopatías , Inhibidores de Prolil-Hidroxilasa , Barbitúricos , Femenino , Glicina/efectos adversos , Glicina/análogos & derivados , Glicina/farmacocinética , Humanos , Hepatopatías/metabolismo , Masculino , Inhibidores de Prolil-Hidroxilasa/efectos adversos , Inhibidores de Prolil-Hidroxilasa/farmacocinéticaRESUMEN
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses. METHODS: This was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters. RESULTS: Co-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups. CONCLUSION: Co-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00519480 . Registered:22 August 2007.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Pirazoles/administración & dosificación , Adulto , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Interacciones Farmacológicas , Quimioterapia Combinada , Ayuno/sangre , Ayuno/metabolismo , Femenino , Glucósidos/efectos adversos , Glucósidos/farmacocinética , Humanos , Hipoglucemiantes/efectos adversos , Insulina/sangre , Ácido Láctico/sangre , Masculino , Metformina/efectos adversos , Metformina/farmacocinética , Persona de Mediana Edad , Pirazoles/efectos adversos , Pirazoles/farmacocinéticaRESUMEN
Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2-period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([14 C]-GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was ≈95% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that ≈80% of daprodustat was absorbed across the gastrointestinal tract, and ≈18% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (≈66%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.
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Barbitúricos , Glicina , Disponibilidad Biológica , Estudios Cruzados , Glicina/análogos & derivados , Humanos , MasculinoRESUMEN
Previous studies have reported that biofilm extracted from full-scale biofilters can serve as nitrogenous disinfection by-product (N-DBP) precursors. Detached biofilm materials could escape during filter ripening and form N-DBP upon chloramination. This study examined the potential breakthrough of biofilm and N-DBP precursors during filter ripening at two water treatment plants (WTPs). The presence of biofilm material in aqueous samples was estimated by total adenosine triphosphate (tATP) levels; N-DBP formation potential (FP) tests were conducted under uniform formation conditions to quantify N-nitrosodimethylamine (NDMA) and haloacetonitrile (HAN4) precursors. While tATP peaks in filter effluent were observed post backwash at both WTPs, temporary increases of effluent NDMA FP were only observed during filter ripening where particle-associated NDMA precursors served as the dominant contributor. Overall, biofilters examined in this study demonstrated a consistent removal of NDMA FP regardless of the filter ripening process.
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Contaminantes Químicos del Agua , Purificación del Agua , Dimetilnitrosamina , Desinfección , NitrógenoRESUMEN
"Effective Enzyme Activity", or simply "Effective Activity", is proposed as a biofiltration monitoring tool which combines enzyme activity with empty bed contact time (EBCT) to quantify biodegradation potential. The primary objective of this study was to evaluate the applicability of the Effective Activity concept for predicting water quality in biofiltration systems. This pilot-scale study evaluated eight different biofilter configurations in order to quantify impacts associated with filter media (anthracite/sand or granular activated carbon), pre-treatment (settled water with or without ozonation) and operating conditions (15- and 30-min EBCT, and backwash with or without chlorine). Microbial characterization included biomass concentration, as measured by adenosine triphosphate (ATP), in addition to esterase and phosphatase activity. Water quality parameters included dissolved organic carbon (DOC), trihalomethane (THM) formation potential (FP), haloacetic acid (HAA) FP, haloacetonitrile (HAN) FP, iodinated DBP FP (THMs and HAAs) and inorganic nutrients (phosphorus and nitrogen). Results confirmed the benefits to treated water quality associated with the application of an ozone residual of 0.5 mg/L, utilization of GAC filter media, eliminating chlorinated backwash, and extending EBCT. This study demonstrated a good relationship between effective esterase activity and reductions in DOC and THM FP, including those systems which incorporate pre-ozonation. As such, this study showed that Effective Activity may be appropriate for relating biomass characterization to treated water quality and highlights the importance of quantifying biomass activity in addition to quantity.
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Ozono , Contaminantes Químicos del Agua/análisis , Purificación del Agua , Desinfección , Filtración , TrihalometanosRESUMEN
Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.
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Lesiones Traumáticas del Encéfalo/complicaciones , Oxigenoterapia Hiperbárica , Síndrome Posconmocional/complicaciones , Síndrome Posconmocional/terapia , Adulto , Anciano , Femenino , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Disinfection byproduct precursors (DBPs) were removed from raw surface water obtained from two Canadian drinking water treatment plants via adsorption to two regenerable linear engineered TiO2 nanomaterials (LENs). The temperature employed in the final heating step of the LEN synthesis procedure was varied to produce two distinct nanomaterials, NB 550 and NB 700. The LENs had similar dimensions but differed in terms of surface characteristics, surface area, and crystal structure. Unlike the commercial TiO2 nanoparticles, both LENs were easily removed from the treated water via settling or filtration. Although neither of the LENs were as effective for NOM adsorption as commercial nanoparticles, both were able to remove substantial amounts of DBP precursors. NB 550 reduced the trihalomethane (THM) formation potential of both water sources by up to 40% and their haloacetic acid (HAA) formation potential by approximately 50%. NB 700 reduced the THM formation potential of one water source by 25% and that of the other by 40%. HAA precursor removal by NB 700 ranged from 25% to 30%. The adsorption of DOC, UV254, THM precursors, and HAA precursors by commercial nanoparticles and the LENs fit a modified Freundlich adsorption isotherm model. When the LENs were regenerated via exposure to UVA light they experienced a gradual loss in adsorption capacity of up to 50% over five regeneration cycles. This loss occurred more quickly for the less photoactive of the two nanomaterials, and was affected by water source, suggesting that components of the water matrices may have interfered with regeneration.
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Adsorción , Agua Potable/química , Purificación del Agua/métodos , Canadá , Desinfección , Filtración , Nanopartículas/química , Compuestos Orgánicos/aislamiento & purificación , Titanio , Rayos Ultravioleta , Contaminantes Químicos del Agua/análisisRESUMEN
The photolysis of chlorine by UV light leads to the formation of the hydroxyl radicals (OH) as well as reactive chlorine species (RCS) that can be effective as advanced oxidation processes (AOPs) for water treatment. Much of the research to date has been done at laboratory- or bench-scale. This study reports results from a model that demonstrates that the relative effectiveness of the UV/Cl2 AOP compared to the more traditional UV/H2O2 AOP is a function of optical path length. As such, the relative effectiveness of the two treatment options evaluated at small scale may not reflect the relative performance at full-scale, making results previously obtained at small-scale potentially less scalable. This study therefore compares the performance of UV/Cl2 to UV/H2O2 at a full-scale water treatment plant, using sucralose and caffeine as spiked surrogates for contaminants that are reactive solely to OH radicals, and to both OH and RCS, respectively. pH was varied between 6.5 and 8.0. The results demonstrated that when using a medium pressure UV lamp, UV/Cl2 might lead to approximately twice the production of OH radicals as UV/H2O2 at pH 6.5 when using the same molar oxidant concentration, but adding chlorine to the UV reactor at pH 8.0 had a negligible impact on OH radical concentration in comparison to UV alone. The study also confirmed previous small-scale results that RCS can be a major contributor to UV/Cl2 treatment for compounds such as caffeine that are susceptible to RCS, with UV/Cl2 effective at both pH 6.5 and 8.0 for such compounds. Disinfection byproducts were monitored, with adsorbable organohalide (AOX) formation increasing by approximately 10⯵g-Cl/L due to chlorine photolysis, but only at pH 6.5 and not at pH 8.0. This implies that UV/Cl2 might increase AOX mostly due to reaction between OH and organic precursors to make them more reactive with chlorine, and not due to RCS. The formation of specific DBPs of current or emerging regulatory interest was minimal under all conditions, except for chlorate. Chlorate yields were in the order of 6-18% of the photolysed chlorine.
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Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Desinfección , Peróxido de Hidrógeno , Oxidación-Reducción , Rayos UltravioletaRESUMEN
Drinking water treatment using UV/H2O2 advanced oxidation typically results in residual H2O2 that requires quenching to minimize its interference with downstream processes. Chemical quenching using chlorine or bisulfite are options, but there is some uncertainty in the literature about the kinetics of the bisulfite reaction, with some reports quoting the reaction as fast, and others as slow. Part of the contradictory information may be due to interference in H2O2 analysis by bisulfite. An analytical method was developed to avoid this interference, in which monochloramine first selectively quenched bisulfite, and then H2O2 was measured spectrometrically using titanium(IV) oxysulfate for color development. The confirmatory experiments suggested that the bisulfite reaction with H2O2 is actually relatively slow, with a half-life in the order of hours to days depending on the pH and the reagent concentrations. As a result, within the typical pH range of drinking water treatment (e.g., 6-9), chlorine is preferred over bisulfite as the H2O2 quenching agent on the basis of reaction kinetics. However, a decrease in pH will lead to an increase in the bisulfite-H2O2 reaction rate along with a decrease in the Cl2-H2O2 reaction rate, such that at pHâ¯<â¯5.7 bisulfite is the faster reagent. Both bisulfite and chlorine were observed to react with H2O2 following a stoichiometric ratio of 1:1 in the natural water matrix tested.
Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Peróxido de Hidrógeno , Oxidación-Reducción , Sulfitos , Rayos UltravioletaRESUMEN
Biofiltration has been shown to be effective for disinfection by-product (DBP) precursor control, however few studies have considered its role in the potential formation of DBPs. Biofilm is composed of heterogeneous bacteria as well as extracellular polymeric substances (EPS). The objective of this study was to determine the contribution of biofilm-related materials such as EPS to form nitrogen-containing DBPs upon chloramination, and to determine the influence of cyclical (scheduled on-off) biofilter operation on DBP precursor removal. Biologically active media was sampled from a full-scale biofilter operating under cold-water conditions (3.6⯱â¯0.5⯰C) and extracted using a cation exchange resin into a phosphate buffer solution. Biomass concentrations, as determined using adenosine triphosphate (ATP) measurements, remained stable at 298⯱â¯55â¯ng ATP/g media over the trial period. N-nitrosodimethylamine (NDMA) and haloacetonitrile (HAN4) formation potential (FP) tests conducted under uniform formation conditions (UFC) using extracted biofilm yielded 0.80⯱â¯0.27â¯ng NDMA/g media and 18.7⯱â¯3.3â¯ng dichloroacetonitrile (DCAN)/g media. Further analyses of extracted biofilm using fluorescence spectroscopy and liquid chromatography-organic carbon detection indicated the presence of proteins above 20â¯kDa and humic-like substances. Extracted proteins (93.5⯱â¯8.1⯵g/g media) correlated well (Râ¯=â¯0.90) with UV 280 measurements, indicating that spectrophotometry may serve as a valuable tool to quantify proteins in extracted biofilms. While substances in biofilms can serve as NDMA and DCAN precursors, the full-scale cyclically-operated biofilter that was examined did not show release of NDMA precursors during start-up following stagnation periods of 6â¯h or more. These biofilters consistently removed 6.9⯱â¯4.3â¯ng/L of NDMA precursors; typical NDMA UFC-FP of biofilter effluent was 8.5⯱â¯2.6â¯ng/L.
Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Biopelículas , Dimetilnitrosamina , Desinfección , NitrógenoRESUMEN
The objective of this pilot study was to evaluate the impact of cyclical (operated 8-12â¯h per day) and continuous biofilter operation with respect to biomass development, biological enzyme activity and treated water quality (in terms of organics, nutrients and disinfection by-product (DBP) formation potential). Continuously operated biofilters developed greater densities of biomass, as measured by ATP, when compared to cyclically operated filters; reducing the empty bed contact time (EBCT) increased biomass density under continuous flow conditions. However, once normalized to biomass, it was shown that cyclically operated filters exhibited higher enzyme activity, indicating that this method of operation may improve bacterial function. Reduction of organics was generally similar for both continuous and cyclical filters with the same EBCT, however, cyclical filters demonstrated higher variability during the first 4â¯h following start-up. Overall, HAA formation potential was better controlled by continuously operated filters, due to poor performance by the cyclical filters upon start-up while THM precursors were removed equally well by all filters. To understand the removal capacity for NDMA precursors through biological filters, both naturally occurring NDMA FP and NDMA FP resulting from spiked anthropogenic precursors was monitored through the filter depth. All the filters removed 90% of the naturally occurring NDMA FP within the first 45â¯cm; cyclical operation resulted in higher reduction of spiked anthropogenic NDMA precursors (50% higher than continuously operated) demonstrating the advantage of routine shut down on overall microbial activity. Tools to monitor and predict biofilter performance are in high demand. Here we present an "effective activity" term which combines enzyme activity with contact time (EBCT). Effective esterase activity was strongly correlated to DOC reduction as a function of filter operation (cyclical or continuous) and EBCT; effective phosphatase activity was indicative of phosphate removal. The results of this study indicate that routine shut down of the filters as this location improved enzyme activity without compromising control of chlorinated DBPs (THMs and HAAs) or NDMA derived from natural and anthropogenic precursors.