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© 2020 Wiley Periodicals, Inc.The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib. © 2020 John Wiley & Sons Ltd.OBJECTIVE To delineate the epileptic phenotype of LAMA2-related muscular dystrophy (MD) and correlate it with the neuroradiological and muscle biopsy findings, as well as the functional motor phenotype. METHODS Clinical, electrophysiological, neuroradiological, and histopathological data of 25 patients with diagnosis of LAMA2-related MD were analyzed. RESULTS Epilepsy occurred in 36% of patients with LAMA2-related MD. Mean age at first seizure was 8 years. The most common presenting seizure type was focal-onset seizures with or without impaired awareness. Visual aura and autonomic signs, including vomiting, were frequently reported. Despite a certain degree of variability, bilateral occipital or temporo-occipital epileptiform abnormalities were by far the most commonly observed. Refractory epilepsy was found in 75% of these patients. Epilepsy in LAMA2-related MD was significantly more prevalent in those patients in whom the cortical malformations were more extensive. Merbarone price In contrast, the occurrence of epilepsy was not found to be associated with the patients' motor ability, the size of their white matter abnormalities, or the amount of residual merosin expressed on muscle. SIGNIFICANCE The epileptic phenotype of LAMA2-related MD is characterized by focal seizures with prominent visual and autonomic features associated with EEG abnormalities that predominate in the posterior quadrants. A consistent correlation between epileptic phenotype and neuroimaging was identified, suggesting that the extension of the polymicrogyria may serve as a predictor of epilepsy occurrence. © 2020 International League Against Epilepsy.In phosphate (Pi)-deprived Arabidopsis (Arabidopsis thaliana), phosphatidylglycerol (PG) is substituted by sulfolipid for maintaining Pi homeostasis. Sulfoquinovosyl diacylglycerol1 (AtSQD1) encodes a protein, which catalyzes uridine diphosphate glucose (UDPG) and sulfite (SO3 2- ) to UDP-sulfoquinovose, which is a key component in the sulfolipid biosynthetic pathway. In this study, a reverse genetics approach was employed to decipher the function of the AtSQD1 homolog OsSQD1 in rice. Differential expressions of OsSQD1 in different tissue and response to -P and -S also detected, respectively. The in vitro protein assay and analysis suggests that OsSQD1 is a UDP-sulfoquinovose synthase. Transient expression analysis showed that OsSQD1 is located in the chloroplast. The analyses of the knockout (ossqd1) and knockdown (Ri1 and Ri2) mutants demonstrated reductions in Pi and total P concentrations, 32 Pi uptake rate, expression levels of Pi transporters and altered developmental responses of root traits, which were accentuated during Pi deficiency. The inhibitory effects of the OsSQD1 mutation were also evident in the development of reproductive tissue. Furthermore, OsSQD1 differently affects lipid composition under different Pi regime affects sulfur (S) homeostasis. Together, the study revealed that OsSQD1 affects Pi and S homeostasis, and lipid composition in response to Pi deprivation. © 2020 John Wiley & Sons Ltd.Species coexistence in grasslands is regulated by several environmental factors and interactions with the soil microbial community. Here, the development of the Basidiomycetes fungus Agaricus arvensis, forming fairy rings, in a species-rich Mediterranean grassland, is described. Effects of the mycelial front on plants, fungi, and bacteria were assessed by vegetation survey and next generation sequencing approaches. Our results showed a fungal-dependent shift in the community structure operated by a wave-like spread of fairy rings that decreased plant, fungal and bacterial diversity, indicating a detrimental effect of fairy rings on most species. The fairy rings induced successional processes in plants that enhanced the replacement of a community dominated by perennial plants with short living and fast-growing plant species. In parallel, fungal and bacterial communities showed evident differences in species composition with several taxa associated within distinct sampling zone across the fairy rings. Notably, Bacteria belonging to the Burkholderia genus and fungi of the genus Trichoderma increased in response to the advancing mycelium of A. arvensis. The profound changes in community composition and the overall increase in taxa diversity at ecosystemic scale suggest that fairy ring forming fungi may act as ecosystem engineer species in Mediterranean grasslands. This article is protected by copyright. All rights reserved.PURPOSE To estimate the risk for bladder and rectal cancer induction due to standard fractionated (SF) and moderately hypofractionated (HF) volumetric modulated arc therapy (VMAT) for prostate carcinoma. METHODS Twelve patients with low or intermediate-risk of prostate cancer referred for external-beam radiotherapy were included in this study. Three computed tomography-based VMAT plans were created for each study participant. The first plan was generated by assuming patient's irradiation with SF-VMAT (78 Gy in 39 fractions). The second and third plans were created on the basis of two different HF schedules (HF-VMAT1 70 Gy in 30 fractions, HFVMAT2 60 Gy in 20 fractions). Data from differential dose-volume histograms obtained by the above treatment plans were employed to calculate the organ equivalent dose (OED) of the bladder and rectum with the aid of a non-linear model accounting for fractionation and proliferation effects. The calculated OED values were used to estimate the average lifetime attributable risk (LARav ) for the appearance of radiotherapy-induced secondary bladder and rectal malignancies.