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Water Research Jun 2023Micropollutant (MP) abatement efficiencies are critical information for optimizing water treatment process for cost-effective operations. Nevertheless, due to the vast...
Micropollutant (MP) abatement efficiencies are critical information for optimizing water treatment process for cost-effective operations. Nevertheless, due to the vast number of MPs in real water matrices, it is infeasible to measure their abatement efficiencies individually in practical applications. In this study, a probe compound-based kinetic model was developed for generalized prediction of MP abatement in various water matrices by the ultraviolet (UV)/chlorine process. The results show that by measuring the depletion of three probe compounds (ibuprofen, primidone, and dimetridazole) spiked in the water matrix, the exposures of main reactive chlorine species (RCS including chlorine radicals (Cl•), dichloride radicals (Cl•) and chlorine oxide radicals (ClO•)) and hydroxyl radicals (•OH) during the UV/chlorine process could be calculated using the model. Based on the determined exposures, the abatement efficiencies of various MPs in different water matrices (e.g., surface water, groundwater, and wastewater) could generally be predicted with acceptable accuracy by the model without prior water-specific calibration. In addition, the relative contribution of UV photolysis and oxidation with active chlorine, RCS, and •OH to MP abatement could be quantitatively simulated using the model to clarify the abatement mechanism of MPs during the UV/chlorine process. The probe-based kinetic model can thus offer a useful tool to guide practical water and wastewater treatment for MP abatement and to explore the mechanism of UV/chlorine process.
Topics: Chlorine; Water Pollutants, Chemical; Ultraviolet Rays; Wastewater; Hydrogen Peroxide; Chlorides; Oxidation-Reduction; Kinetics; Water Purification
PubMed: 37098285
DOI: 10.1016/j.watres.2023.119985 -
Plant Physiology and Biochemistry : PPB May 2023γ-Aminobutyric acid (GABA) plays significant metabolic and signaling roles in plant stress responses. Recent studies have proposed that GABA alleviates plant nitrogen...
γ-Aminobutyric acid (GABA) plays significant metabolic and signaling roles in plant stress responses. Recent studies have proposed that GABA alleviates plant nitrogen (N) deficient stress; however, the mechanism by which GABA mediates plant N deficiency adaptation remains not yet well understood. Herein we found in a medicinal plant Andrographis paniculata that 5 mmol L exogenous GABA promoted plant growth under N deficient (1 mmol L NO) condition, with remarkably increments in total N and NO concentrations in plants. GABA increased N assimilation and protein synthesis by up-regulating the activities and expression of N metabolic enzymes. GABA also increased the accumulation of α-ketoglutarate and malate, which could facilitate the assimilation of NO. Inhibition of NR by NaWO counteracted the promoting effects of GABA on plant growth, and the effects of GABA were not affected by L-DABA and 3-MP, the inhibitors of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD), respectively. These results suggested that the nutritional role of GABA was excluded in promoting plant growth under low N condition. The results of N isotopic tracing and NRTs transcription indicated that exogenous GABA could up-regulate NRT2.4 and NRT3.2 to increase plant NO uptake under N deficient condition. Interestingly, primidone, an inhibitor of GABA receptor, impeded the effects of GABA on plant growth and N accumulation. Thus, our results revealed that exogenous GABA acted as a signal to up-regulate NRTs via its receptor to increase NO uptake, and subsequently promoted NO assimilation to alleviate N deficiency in A. paniculata.
Topics: Seedlings; Nitrates; Andrographis paniculata; Nitrogen; Plant Roots; gamma-Aminobutyric Acid
PubMed: 37086691
DOI: 10.1016/j.plaphy.2023.107700 -
SAGE Open Medical Case Reports 2023Canavan disease is a rare fetal inherited leukodystrophy, caused by accumulation of N-acetyl-aspartate in the brain. Here, we report a child presented with frequent...
Canavan disease is a rare fetal inherited leukodystrophy, caused by accumulation of N-acetyl-aspartate in the brain. Here, we report a child presented with frequent intractable seizures and visual impairment. A 14-month-old female infant with a complaint of the absence of neck holding and generalized tonic-clonic seizures was referred to our hospital. Macrocephaly, setting sun eyes, tremor, and hypotonia were observed. Funduscopy showed optic atrophy. Our patient's flash visual evoked potential showed blindness. Her brain magnetic resonance imaging showed diffuse white matter in subcortical, basal ganglia, and dorsal pons. Electroencephalography showed diffuse slow and sharp waves. The genetic study detected a hemizygous mutation in the aspartoacylase gene. Our patient was diagnosed with Canavan disease and began anticonvulsant treatment. However, seizures were not under control. Then, her medications were discontinued, and clobazam and primidone were administered. In conclusion, starting clobazam and primidone may help prevent frequently intractable seizures in Canavan disease patients.
PubMed: 36968992
DOI: 10.1177/2050313X231160885 -
Water Research May 2023Emerging micropollutants (µPs) appearing in water bodies endanger aquatic animals, plants, microorganisms and humans. The nonthermal plasma-based advanced oxidation...
Emerging micropollutants (µPs) appearing in water bodies endanger aquatic animals, plants, microorganisms and humans. The nonthermal plasma-based advanced oxidation process is a promising technology for eliminating µPs in wastewater but still needs further development in view of full-scale industrial application. A novel cascade reactor design which consists of an ozonation chamber preceding a dielectric barrier discharge (DBD) plasma reactor with a falling water film on an activated carbon textile (Zorflex®) was used to remove a selection of µPs from secondary municipal wastewater effluent. Compare to previous plasma reactor, molecular oxidants degraded micropollutants again in an ozonation chamber in this study, and the utilization of different reactive oxygen species (ROS) was improved. A gas flow rate of 0.4 standard liter per minute (SLM), a water flow rate of 100 mL min, and a discharge power of 25 W are identified as the optimal plasma reactor parameters, and the µP degradation efficiency and electrical energy per order value (EE/O) are 84-98% and 2.4-5.3 kW/m³, respectively. The presence of ROS during plasma treatment was determined in view of the µPs removal mechanisms. The degradation of diuron (DIU), bisphenol A (BPA) and 2-n-octyl-4-isothiazolin-3-one (OIT) was mainly performed in ozonation chamber, while the degradation of atrazine (ATZ), alachlor (ALA) and primidone (PRD) occurred in entire cascade system. The ROS not only degrade the µPs, but also remove nitrite (90.5%), nitrate (69.6%), ammonium (39.6%) and bulk organics (11.4%). This study provides insights and optimal settings for an energy-efficient removal of µPs from secondary effluent using both free radicals and molecular oxidants generated by the plasma in view of full-scale application.
Topics: Humans; Wastewater; Oxidants; Reactive Oxygen Species; Water; Ozone; Water Pollutants, Chemical; Water Purification
PubMed: 36963308
DOI: 10.1016/j.watres.2023.119881 -
Epilepsia May 2023Developmental and epileptic encephalopathy with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a...
Developmental and epileptic encephalopathy with continuous spike-and-wave activation in sleep (CSWS) or DEE-SWAS is an age-dependent disease, often accompanied by a decline in cognitive abilities. Early successful treatment of CSWS is associated with a better cognitive outcome. We retrospectively analyzed the clinical, electrophysiological, radiological, and genetic data of children with DEE-SWAS associated with melastatin-related transient receptor type 3 gene (TRPM3) missense variants. We report two unrelated children with pharmacoresistant DEE-SWAS and developmental delay/regression and different heterozygous de novo missense variants in the TRPM3 gene (NM_001366145.2; c.3397 T > C/p.Ser1133Pro, c.2004G > A/p.Val1002Met). The variant p.Val1002Met (previously known as p.Val990Met or p.Val837Met) and p.Ser1133Pro were recently shown to result in a gain-of-function effect. Based on this finding, previous drug resistance, and the experimentally demonstrated inhibitory effect of primidone on TRPM3, we initiated an individualized therapy with this drug. In both children, developmental regression was stopped, psychomotor development improved, and CSWS was no longer detectable. To our knowledge, this is the first report of a treatment with primidone in TRPM3-associated CSWS. Our results highlight the importance of early genetic diagnosis in patients with epilepsy and the possibility of precision medicine, which should be considered in the future in individuals with a TRPM3-linked DEE-SWAS.
Topics: Humans; Female; Primidone; Epilepsy; Retrospective Studies; HEK293 Cells; Electroencephalography; Anticonvulsants; Male; Child, Preschool; Child
PubMed: 36929095
DOI: 10.1111/epi.17586 -
Water Research May 2023Pharmaceutical and personal care products (PPCPs) are frequently detected in water bodies and have potential risks to human health and the ecosystem. The degradation of...
Pharmaceutical and personal care products (PPCPs) are frequently detected in water bodies and have potential risks to human health and the ecosystem. The degradation of eight structurally diverse PPCPs by ammonia/chlorine was systematically investigated in this study. Compared with chlorination, ammonia/chlorine markedly enhanced PPCP degradation, and the degradation efficiencies of most PPCPs were greater than 70%. Tert-butanol strongly suppressed PPCP degradation, while bicarbonate suppressed it moderately, suggesting the importance of ClO⋅and ⋅CO in PPCP degradation. In neutral conditions, PPCP degradation was mainly attributed to ⋅OH, with its contribution ranging from 74% to 100% at a Cl/N molar ratio of 1.6. Regarding the effect of natural organic matter, atrazine and primidone were inhibited the most, while carbamazepine (CBZ), metoprolol (MTP), and atenolol (ATN) were affected the least. PPCP degradation was suppressed in reclaimed water; the degradation of CBZ, MTP, and ATN was suppressed the least, with degradation efficiencies of 77.1%-85.4%, 75.1%-77.1%, and 64.6%-68.8%, respectively. Furthermore, compared with chlorination, fewer volatile halogenated byproducts were formed in reclaimed water when using the ammonia/chlorine process, and the concentration of each byproduct formed by ammonia/chlorine was less than 10 µg/L. This study suggests the feasibility of using ammonia/chlorine oxidation to degrade PPCPs in reclaimed water.
Topics: Humans; Chlorine; Ammonia; Water Purification; Ecosystem; Water Pollutants, Chemical; Ultraviolet Rays; Water; Carbamazepine; Chlorides
PubMed: 36924555
DOI: 10.1016/j.watres.2023.119862 -
The Science of the Total Environment Jun 2023Electrochemical process coupling with ultraviolet light-emitting diode for micropollutant abatement was evaluated in the treatment of wastewater containing Cl. Four...
Insight into micropollutant abatement during ultraviolet light-emitting diode combined electrochemical process: Reaction mechanism, contributions of reactive species and degradation routes.
Electrochemical process coupling with ultraviolet light-emitting diode for micropollutant abatement was evaluated in the treatment of wastewater containing Cl. Four representative micropollutants, atrazine, primidone, ibuprofen and carbamazepine, were selected as target compounds. The impacts of operating conditions and water matrix on micropollutant degradation were investigated. Fluorescence excitation-emission matrix spectroscopy spectra and high performance size exclusion chromatography were employed to characterize the transformation of effluent organic matter in treatment. The degradation efficiencies of atrazine, primidone, ibuprofen and carbamazepine are 83.6 %, 80.6 %, 68.7 % and 99.8 % after 15 min treatment, respectively. The increment of current, Cl concentration and ultraviolet irradiance promote the micropollutant degradation. However, the presence of bicarbonate and humic acid inhibit micropollutant degradation. The mechanism of micropollutant abatement was elaborated based on reactive species contributions, density functional theory calculation and degradation routes. Free radicals (HO, Cl, ClO and Cl) could be generated by chlorine photolysis and subsequent propagation reactions. The concentrations of HO and Cl are 1.14 × 10 M and 2.0 × 10 M in optimal condition, respectively, and the total contributions of HO and Cl for the degradation of atrazine, primidone, ibuprofen and carbamazepine are 24 %, 48 %, 70 % and 43 %, respectively. The degradation routes of four micropollutants are elucidated based on intermediate identification, Fukui function and frontier orbital theory. Micropollutants can be effectively degraded in actual wastewater effluent, and the small molecule compound proportion increases during effluent organic matter evolution. Compared with photolysis and electrolysis, the coupling of the two processes has potential for energy saving in micropollutant degradation, which shed light on the prospects of ultraviolet light-emitting diode coupling with electrochemical process for effluent treatment.
PubMed: 36914136
DOI: 10.1016/j.scitotenv.2023.162798 -
Epilepsia Open Sep 2023Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions...
Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty-one individuals (median age [Q -Q ]: 15 [6.5-28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug-resistance (3435 CC) or drug-sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs.
Topics: Humans; Anticonvulsants; Pharmacogenetics; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C19; Pilot Projects; Cytochrome P-450 CYP2C9; Saliva; Epilepsy; Phenytoin; Clobazam; Phenobarbital
PubMed: 36840436
DOI: 10.1002/epi4.12717 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Neurology Jun 2023A 66-year-old man with seizures that started at 61 years eventually developed drug-resistant epilepsy and was managed with medications and vagal nerve stimulation. The...
A 66-year-old man with seizures that started at 61 years eventually developed drug-resistant epilepsy and was managed with medications and vagal nerve stimulation. The patient had a convulsive event at 61 years, followed by recurrent events of confusion and speech arrest lasting 30-120 seconds. He underwent gadolinium-enhanced brain MRI and angiogram, which revealed pial enhancement in the right occipital, parietal, and posterior temporal regions with subcortical atrophy. CSF findings were unremarkable. Continuous video EEG showed electroclinical correlation for his episodes of confusion and speech arrest with recurrent brief runs of rhythmic delta from the right temporal region with evolution and spread to the entire right hemisphere. The patient tried multiple antiseizure medications including valproic acid, topiramate, phenytoin, carbamazepine, levetiracetam, brivaracetam, and lamotrigine without success. He was eventually put on a combination of lacosamide, zonisamide, clonazepam, and primidone, which helped to a certain extent, but the patient continued to have daily episodes and 10-12 electroclinical seizures noted on a follow-up 24-hour ambulatory EEG. Follow-up brain MRI with contrast confirmed the diagnosis. Phase II intracranial monitoring for surgical management was offered to the patient, which he deferred because of risks. Vagal nerve stimulator (VNS) was also offered as a palliative therapy to which the patient agreed. Gradual titration in VNS settings over 1 year helped to achieve seizure freedom. Presentation of focal seizure with this type of atypical etiology is rare. Typically, surgical management is used to achieve seizure freedom in this condition; successful management with VNS has not been reported so often.
Topics: Male; Humans; Middle Aged; Aged; Drug Resistant Epilepsy; Seizures; Vagus Nerve Stimulation; Brain; Clinical Reasoning; Treatment Outcome
PubMed: 36792377
DOI: 10.1212/WNL.0000000000206890