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Intervention studies have demonstrated that the n-3 fatty acids, docosahexaenoic and eicosapentaenoic acids, ameliorate seizure frequency in patients with drug-resistant epilepsy (DRE). There is a scarcity of fatty acid status of patients with epilepsy. We have investigated blood fatty acids of patients with DRE and assessed the indices of elongase and desaturase activities. DRE patients (n = 83) and healthy controls (n = 31) were recruited form Soba University Hospital Neurology Referral Clinic and Ibn-Auf paediatric Teaching Hospital Neurology Referral Clinic, Khartoum, Sudan. Fatty acid composition of plasma total lipids, phosphatidylcholine and neutral lipids were analysed. The patients compared with their healthy counterparts had higher levels of C140, C160, C180, C200, C220 (p0.05) lower in the patients with drug-resistant epilepsy than in the healthy control subjects. DRE is associated with blood fatty acid perturbation and abnormal activities of long-chain fatty acid elongase (ELOVL-6), stearoyl-coenzyme A desaturase-1 (SCD-1), delta 6-fatty acid desaturase (D6D) and delta 5 fatty acid desaturase (D5D). N-3 fatty acids are known to ameliorate seizures frequency and dampen neuronal hyperexcitability. Therefore, patients with DRE should be regularly monitored and, if necessary, supplemented with n-3 fatty acids.
The tyrosine kinase inhibitor nintedanib reduces the rate of decline in forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). The recommended dose of nintedanib is 150mg twice daily (BID).
Data from Phase II and III trials in IPF, SSc-ILD and progressive fibrosing ILDs other than IPF were analyzed to investigate the relationship between nintedanib plasma concentrations (exposure) and efficacy.
Using data from 1403 patients with IPF treated with 50-150mg nintedanib BID in Phase II and III studies, a linear disease progression model with a maximum drug effect on the rate of decline in FVC was established. Age, height and gender were pre-specified covariates on baseline FVC. Stepwise analysis revealed no other covariates with a distinct effect on the exposure-efficacy relationship. The estimated plasma concentration producing 80% of the maximum drug effect was 10-13ng/mL, close to the median exposure at 150mg BID (10ng/mL). The model in IPF was adapted using Phase III data from 575 patients with SSc-ILD and 663 patients with progressive fibrosing ILDs other than IPF. Besides differences in the natural decline in FVC without treatment, data were consistent with the exposure-efficacy relationship in IPF.
For most patients with chronic fibrosing ILDs, the 150mg nintedanib BID dose provides exposure levels associated with a therapeutic effect close to the maximum nintedanib effect independent of disease condition or baseline demographics.
For most patients with chronic fibrosing ILDs, the 150 mg nintedanib BID dose provides exposure levels associated with a therapeutic effect close to the maximum nintedanib effect independent of disease condition or baseline demographics.In neuromuscular disorders (NMDs), nocturnal non-invasive ventilation (NIV) via a nasal mask is offered when hypercapnic respiratory failure occurs. With disease progression, nocturnal NIV needs to be extended into the daytime. Mouthpiece ventilation (MPV) is an option for daytime NIV. MPV represents a difficult task for home ventilators due to rapidly changing load conditions resulting from intermittent connections and disconnections from MPV circuit. The 252nd ENMC International Expert Workshop, held March 6th to 8th 2020 in Amsterdam, reported general guidelines for management of daytime MPV in NMDs. This report could not present all the detail regarding the technical issues important for clinical success of MPV. Based on the expert workshop discussions and the evidence from existing studies, the current narrative review aims to identify the technical issues of MPV and offers guidance via a decisional algorithm and educational figures providing relevant information that is important for successful implementation of MPV.Cadmium (Cd), a heavy metal element has strong toxicity to living organisms. Excessive Cd accumulation directly affects the absorption of mineral elements, inhibits plant tissue development, and even induces mortality. DNA Repair inhibitor Populus × canadensis 'Neva', the main afforestation variety planted widely in northern China, was a candidate variety for phytoremediation. However, the genes relieving Cd toxicity and increasing Cd tolerance of this species were still unclear. In this study, we employed transcriptome sequencing on two Cd-treated cuttings to identify the key genes involved in Cd stress responses of P. × canadensis 'Neva' induced by 0 (CK), 10 (C10), and 20 (C20) mg/L Cd(NO3)2 4H2O. We discovered a total of 2,656 (1,488 up-regulated and 1,168 down-regulated) and 2,816 DEGs (1,470 up-regulated and 1,346 down-regulated) differentially expressed genes (DEGs) between the CK vs C10 and CK vs C20, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in response to the Cd stress indicated that many DEGs identified were involved in the catalytic activity, the oxidoreductase activity, the transferase activity, and the biosynthesis of secondary metabolites. Based on the enrichment results, potential candidate genes were identified related to the calcium ion signal transduction, transcription factors, the antioxidant defense system, and transporters and showed divergent expression patterns under the Cd stress. We also validated the reliability of transcriptome data with the real-time PCR. Our findings deeper the understanding of the molecular responsive mechanisms of P. × canadensis 'Neva' on Cd tolerance and further provide critical resources for phytoremediation applications.Cadmium (Cd) tolerance mechanisms in plant are mainly divided into two categories evasion mechanism and tolerance mechanism. However, due to the complexity of the mechanism of Cd absorption and accumulation in crops, there are still disputes and controversies about Cd toxicity to plants and the mechanism of Cd tolerance in plants. The Cd absorption and accumulation mechanism in edible parts of pepper remains unknown. The present study characterized three pepper cultivars with different cadmium tolerance under cadmium stress. One high-Cd-accumulation type (X55), a medium-Cd-accumulation type (Daguo 99) and a low-Cd-accumulation type (Luojiao 318) were selected to study distribution characteristics of Cd in subcellular fractions of the three pepper varieties as well as expression difference of key Cd accumulation and tolerance genes under different cadmium levels. The results showed that under Cd stress, X55 and Daguo 99 mainly migrated Cd from root to stems and leaves, while Luojiao318 migrated it to the fruit.
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