Search

The environmental impact of the discharge of lithium (Li) by anthropogenic activity has been overlooked. By analyzing Li concentrations and isotope compositions (δ 7 Li) of water and sediment samples, this study evaluates the influence of anthropogenic Li discharge on the Xiaoqing River and Laizhou Bay, which are heavily polluted areas in China. High Li concentrations of the river water (up to 7.8 μmol/L) should be linked to anthropogenic Li discharge. However, no profound δ 7 Li anomalies were observed, preventing identification of the exact discharge sources. In the river sediments, Li concentrations (19.0-45.0 μg/g) were weakly correlated with Zn, Cu, and Cr concentrations, whereas δ 7 Li values ranged from 0.6 ‰ to 13.9 ‰ with high values being accompanied by high contents of total organic carbon and heavy Cr isotope compositions (δ 53 Cr). All these point to significant influence of anthropogenic activity on the Li budget of river sediments. A simple mass balance calculation indicates that smelters, Li-bearing therapeutic drugs, and secondary Li-ion batteries are the main anthropogenic Li sources. In contrast to river sediments, marine sediments in the Laizhou Bay were broadly homogeneous at both spatial and temporal scales, indicating no significant influence of anthropogenic Li discharge. Overall, our data indicate that Li isotope systematics in river sediments, especially sediments near intense anthropogenic activity, are effective at tracing potential Li pollution and can help obtain accurate results for environmental inspection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

X-linked adrenoleukodystrophy (ALD) is a rare peroxisome disease with phenotypic heterogeneity. There is a lack of suitable in vitro models to study its pathogenesis. We established two strains of iPSCs from skin fibroblasts of patients with childhood cerebral ALD and Addison's disease, respectively. CytoTune™2.0 Sendai reprogramming kit was used. The iPSC lines showed typical stem cell morphology, normal karyotype, and carrying ABCD1 variation. The iPSC lines express pluripotency markers, and have the capacity to differentiate into three germ layers. iPSCs can be used as an alternative cell source for ALD in vitro model to study its pathogenesis and therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Infantile spasms (IS) is a common epilepsy syndrome in infancy. Genetically based birth defects are among the many causes of infantile spasms. Genetic diagnosis can reveal the etiology of IS and guide treatment strategies and genetic counseling, but significant challenges surround the choice of appropriate genetic diagnostic strategies to improve the diagnostic yield in IS., Methods: For a cohort of Chinese patients with IS, appropriate genetic testing methods were selected according to etiological classification. Methods included karyotyping, copy number variation detection, single-gene sequencing, targeted sequencing panel, and whole-exome sequencing., Results: A total of 728 children with IS from fifteen provinces and municipalities in China from June 2015 to October 2020 were recruited in the study. Among them, 436 were males (59.9%). The median age was 9.46 months. The diagnostic yield of our study was 31.5% (185/587). The top five causative genes were TSC2 (n = 91), STXBP1 (n = 21), TSC1 (n = 15), SCN2A (n = 6), and CDKL5 (n = 6). The genetic diagnostic yield was 100% in Down syndrome (n = 1), neurofibromatosis (n = 2), and methylmalonic acidemia (n = 2), 83.5% in tuberous sclerosis complex (n = 127), and 16.7% in unsolved infantile spasms (n = 442). Different genetic testing methods for different etiologies show large differences in diagnostic yields., Conclusion: This study demonstrates that appropriate genetic testing procedures for different phenotypes can ensure a high diagnostic yield., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Cocaine as a highly addictive psychostimulant can cause changes in the body at the cellular and molecular levels over a long period of time. It reminds us that cocaine may have a potential role in post-transcriptional regulation, but the alteration of insula-expression profile in adolescent cocaine use disorder (CUD) has not been reported. To reveal the mechanisms underlying the post-transcriptional regulation of cocaine, we investigate the transcriptome in the insula of cocaine-induced mice based on high-throughput strand-specific RNA sequencing. We analyzed the alterations of messenger RNA (mRNA) expression profile in the insula of cocaine-induced condition place preference (CPP) mice and then correlated it with microRNAs to reveal their involvement in the formation of cocaine-induced CPP. In this study, a total of 27786 genes were identified, 5750 new genes (novel expressed transcripts of unannotated in the reference genome) were discovered, among which 1,205 were annotated functionally. A total of 198 differentially expressed genes (DEG) that functioned in synaptic transmission, cholinergic, developmental process, neurotransmitter metabolic process, drug catabolism, cellular response to drug, MAP kinase activity, ceramidase activity, and drug resistance were significantly enriched. Further analysis showed that 26045 mRNAs formed 45,208 network-relationship pairs with 1770 microRNAs. In the current study, our work was the first to reveal that alterations of RNAs in the insula, as a core brain region of the neural circuits of interoception, were involved in the process of cocaine-induced CPP of adolescent mice. These findings enrich the biology and expand the molecular regulatory network related to adolescence CUD. They provided the possibility that some DEGs may be used as novel biomarkers for the diagnosis or evaluation of substance use disorder, and also provided clues for elucidating the neurobiological mechanism of substance use disorder., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the safety of inactivated coronavirus 2019 disease (COVID-19) vaccine in tuberous sclerosis complex (TSC) patients with epilepsy., Methods: All patients with epilepsy were selected from Efficacy and Safety of Sirolimus in Pediatric Patients with Tuberous Sclerosis (ESOSPIT) project and younger than 17 years old. The patients were treated with mTOR inhibitors (rapamycin). A total of 44 patients who completed the two-dose inactivated COVID-19 vaccine between July 7, 2021, and January 1, 2022, were enrolled., Results: The median age of seizure onset was 23 months. About two-thirds of patients have focal seizures. Thirty-three patients use antiseizure medications. The mean duration of rapamycin treatment was 55.59 ± 18.42 months. Adverse reactions within 28 days after injection occurred in 11 patients (25%), all were under 12 years old. Injection site pain was the most reported event (20.45%), which was mild in severity and improved within one day. All patients had no seizure-related changes after vaccination., Conclusion: This study shows that the inactivated COVID-19 vaccine was well tolerated and safe in TSC patients with epilepsy, as well as for those treated with mTOR inhibitors., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The vocal folds (VFs) are a pair of muscles in the larynx that play a critical role in breathing, swallowing, and speaking. VF function can be adversely affected by various medical conditions including head or neck injuries, stroke, tumor, and neurological disorders. In this paper, we propose a deep learning system for automated detection of laryngeal adductor reflex (LAR) events in laryngeal endoscopy videos to enable objective, quantitative analysis of VF function. The proposed deep learning system incorporates our novel orthogonal region selection network and temporal context. This network learns to directly map its input to a VF open/close state without first segmenting or tracking the VF region. This one-step approach drastically reduces manual annotation needs from labor-intensive segmentation masks or VF motion tracks to frame-level class labels. The proposed spatio-temporal network with an orthogonal region selection subnetwork allows integration of local image features, global image features, and VF state information in time for robust LAR event detection. The proposed network is evaluated against several network variations that incorporate temporal context and is shown to lead to better performance. The experimental results show promising performance for automated, objective, and quantitative analysis of LAR events from laryngeal endoscopy videos with over 90% and 99% F1 scores for LAR and non-LAR frames respectively., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy., Methods: A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (<12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint., Results: There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged <6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P<0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P<0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004]., Conclusion: Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: Syntaxin binding protein 1 (STXBP1) plays an important role in the release of synaptic vesicles. STXBP1-related encephalopathy is a brain dysfunction caused by STXBP1 variation. Levetiracetam (LEV) exerts antiepileptic effects by binding to synaptic vesicle protein 2A (SV2A). This study aimed to analyze the prognosis of LEV treatment of STXBP1 encephalopathy (STXBP1-E) and the correlation among genotype, phenotype, and LEV efficacy., Methods: Patients with pathogenic STXBP1 variants were collected from multiple centers, and their clinical history, video electroencephalogram (vEEG) characteristics, imaging examination data, and anti-seizure medication (ASM) history were systematically analyzed. The ASMs related to the prognosis were explored., Results: Forty patients with STXBP1-E were enrolled in this study. The detailed ASM usage of 37 patients was recorded without intervening in ASM selection. At the endpoint of six months treatment, the results of Fisher's exact test showed that in all ASMs, LEV affected the prognosis of patients with STXBP1-E. LEV was effective in improving the partial remission rate but did not achieve seizure freedom. However, LEV monotherapy could achieve seizure freedom in patients with other early-onset epileptic and encephalopathy. For refractory West syndrome (WS) or Ohtahara syndrome (OS), LEV combined with other ASMs could improve the seizure remission rate., Conclusion: LEV increased the seizure reduction rate and improved the vEEG characteristics in patients with STXBP1-E, but not seizure freedom. LEV combined with other ASMs could increase the seizure reduction rate, especially for refractory WS or OS. Thus, LEV could be considered after identifying the pathogenicity of STXBP1 variants., (Copyright © 2021. Published by Elsevier Ltd.)

DDTs were detected in yellowfin tuna (Thunnus albacares, 92.1-221.8 ng‧g -1 lipid weight) and their prey (54.9-93.5 ng‧g -1 lipid weight) from the South China Sea (SCS). DDT levels reported in this study were lower than those of the previous studies indicated the recent mitigation of DDT contamination in the SCS. Higher DDT levels were observed in fat abdominal muscle than lean dorsal muscle in adult yellowfin tuna. Meanwhile, DDT levels in adult yellowfin tuna were higher than the young ones. The composition profiles of DDT and its metabolites suggested DDTs in fish in the SCS were mainly derived from the historical use of technical DDTs. DDTs were biomagnified through food chains with the trophic magnification factor of 2.5. Risk assessment results indicated that dietary exposure to DDTs through lifetime fish consumption from the SCS would pose little cancer and noncarcinogenic risk to coastal residents., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis., Methods: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs., Results: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up., Conclusions: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Tuberous sclerosis (TSC) is an autosomal dominant inherited disease caused by mutations in the TSC1 or TSC2 gene and results in the over-activation of the mammalian target of the rapamycin (mTOR) signaling pathway. Rapamycin, an mTOR inhibitor, is clinically used to treat hamartomatous lesionsas in TSC and its effect on controlling epilepsy is also reported in many studies. This study aims to evaluate the risk factors of pharmacoresistant epilepsy in patients with TSC receiving long-term rapamycin treatment., Method: A total of 108 patients with TSC taking rapamycin for over 1 year were enrolled in this study. Factors that might influence seizure control were statistically analyzed by multiple factor analysis. A subgroup analysis was also conducted to access the relationship between calcified epileptic foci and pharmacoresistant epilepsy. (Clinical trial registration number: ChiCTR-OOB-15006535(2015-05-29))., Results: Seizure was controlled in 53 patients but was not managed in 55 patients considered to be drug resistant. Logistic regression analysis showed that calcification in the cerebral parenchyma was a risk factor of pharmacoresistant epilepsy [P = 0.006, odds ratio (OR) = 4.831 (1.577, 14.795)]. Fifteen of 17 patients with calcified epileptic foci suffered from pharmacoresistant epilepsy (88.2%). Seizures in patients with calcified epileptic foci were probably pharmacoresistant (P = 0.010)., Conclusion: Calcification in epileptic foci strongly indicates pharmacoresistant epilepsy in patients with TSC even when treated with appropriate anti-epilepsy drugs (AEDs) and rapamycin. Calcification can be used to evaluate pharmacoresistant epilepsy in patients with TSC., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

2-(4-Chlorophenyliminomethyl)-8-hydroxyquinoline was synthesized and crystal data was obtained in the orthorhombic space group P-1, with Z=4. Unit cell parameters a=4.744(7) Å, b=9.981(15) Å, c=27.27(4) Å and V=12915(3) Å(3). In this paper the structural properties and vibrational frequencies of 8-hydroxyquinoline derivative, 2CP8HQ, are studied with the B3LYP and HF methods. Two stable conformers are obtained. The calculated frequencies are in good agreement with the experiment results. It is indicated that both of theoretical calculations were suitable for molecular vibrational frequencies study and the scaled B3LYP method was superior to the scaled HF methods., (Copyright © 2011 Elsevier B.V. All rights reserved.)