Predictors of seizure outcomes in children with tuberous sclerosis complex and intractable epilepsy undergoing resective epilepsy surgery: an individual participant data meta-analysis.

ObjectiveTo perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery.Data sourcesElectronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.Study selectionWe included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion.Data extractionOne author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.Data synthesisTo identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.ResultsOf 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2-8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1-24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4-7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8-13.5, p = 0.002) were associated with a good postoperative seizure outcome.ConclusionsSmall retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review

Comparison of Efficacy of Deep Brain Stimulation of Different Targets in Parkinson's Disease: A Network Meta-Analysis

Background: Deep brain stimulation (DBS) is considered an effective treatment option for Parkinson's disease (PD). Several studies have demonstrated the efficacy of neurostimulation in patients with advanced PD. The subthalamic nucleus (STN), the internal globus pallidus (GPi), ventral intermediate nucleus (Vim), and pedunculopontine nucleus (PPN) are reportedly effective DBS targets for control of Parkinsonian tremors. However, there is no consensus on the ideal target for DBS in patients with Parkinson's disease. Only a few studies have directly compared the efficacy of DBS of the Vim, STN, and GPi. Therefore, we searched PubMed, Embase, Cochrane Library, and other databases for observational studies, extracted data on unified Parkinson's disease rating scale (UPDRS) scores and performed a comprehensive network meta-analysis of different strategies of DBS and compared the efficiency of DBS at different targets.Methods: Forest plot was used to examine the overall efficiency of DBS; cumulative probability value was used to rank the strategies under examination. A node-splitting model was employed to assess consistency of reported outcomes inconsistency. A total of 16 studies which focused on UPDRS improvement were included in the network meta-analysis.Results: By comparing the overall efficiency associated with each target, we confirmed the efficacy of DBS therapy in PD. Our findings revealed similar efficacy of DBS targeted at GPi and STN in the on-medication phase [GPi-3.9 (95% CI −7.0 to −0.96); STN-3.1 (−5.9 to −0.38)]; however, in the off-medication phase, Vim-targeted DBS was associated with better improvement in UPDRS scores and could be a choice as a DBS target for tremor-dominant Parkinsonism.Conclusions: Our findings will help improve clinical application of DBS

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Introductions: Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. Objectives: To identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. Methods: Chondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. Results: Human cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. Conclusions: Our findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment

Untersuchungen uber das Schicksal der in rohes und gekochtes Brunnenwasser gemischten pathogenen Bakterien

Der Verfasser hat Untersuchungen uber die Lebensdauer von pathogenen Darmbakterien, die in rohes und gekochtes Brunnenwasser gemischt wurden, durchgefuhrt. Er hat 5 Brunnenwasser untersucht mit B. typhosus, B. paratyphosus A u. B, B. dysenteriae Komagome A u. B, B. dysenteriae Shiga; die Stamme erhielt Verf. aus dem Staatlichen Institut fur Infektionskrankheiten und aus dem bakteriologischen Institut zu Chiba. Die Ergebnisse sind folgende: 1) war die Menge der verwandten Bakterien klein (ca. 1/3000 Ose in 10 cc.), lebten alle Bakterien in rohem Wasser langer als in gekochtem Wasser. 2) war die Bakterienmenge relativ gross (1 Ose in 10 cc.), lebten die Bakterien zwar langer als bei geringer Menge, verschwanden aber in rohem Wasser schneller als in gekochtem. 3) Unter beiden Versuchsanordnungen lebten die Bakterien im Brunnenwasser langer als in Aq. dest. oder in physiologischer Kochsalzlosung. 4) Die Tabellen zeigen kurz die Ergebnisse: (Autoreferat

Transient dynamics of terrestrial carbon storage : mathematical foundation and its applications

Terrestrial ecosystems have absorbed roughly 30 % of anthropogenic CO2 emissions over the past decades, but it is unclear whether this carbon (C) sink will endure into the future. Despite extensive modeling and experimental and observational studies, what fundamentally determines transient dynamics of terrestrial C storage under global change is still not very clear. Here we develop a new framework for understanding transient dynamics of terrestrial C storage through mathematical analysis and numerical experiments. Our analysis indicates that the ultimate force driving ecosystem C storage change is the C storage capacity, which is jointly determined by ecosystem C input (e.g., net primary production, NPP) and residence time. Since both C input and residence time vary with time, the C storage capacity is time-dependent and acts as a moving attractor that actual C storage chases. The rate of change in C storage is proportional to the C storage potential, which is the difference between the current storage and the storage capacity. The C storage capacity represents instantaneous responses of the land C cycle to external forcing, whereas the C storage potential represents the internal capability of the land C cycle to influence the C change trajectory in the next time step. The influence happens through redistribution of net C pool changes in a network of pools with different residence times. Moreover, this and our other studies have demonstrated that one matrix equation can replicate simulations of most land C cycle models (i.e., physical emulators). As a result, simulation outputs of those models can be placed into a three-dimensional (3-D) parameter space to measure their differences. The latter can be decomposed into traceable components to track the origins of model uncertainty. In addition, the physical emulators make data assimilation computationally feasible so that both C flux- and pool-related datasets can be used to better constrain model predictions of land C sequestration. Overall, this new mathematical framework offers new approaches to understanding, evaluating, diagnosing, and improving land C cycle models.This work was partially done through the working group, Nonautonomous Systems and Terrestrial Carbon Cycle, at the National Institute for Mathematical and Biological Synthesis, an institute sponsored by the National Science Foundation, the US Departmernt of Homeland Security, and the US Department of Agriculture through NSF award no. EF-0832858, with additional support from the University of Tennessee, Knoxville, Research in Yiqi Luo EcoLab was financially supported by US Department of Energy grants DE-SC0008270, DE-SC0014085, and US National Science Foundation (NSF) grants EF 1137293 and OIA-1301789.Ye

MicroRNA Let-7f Inhibits Tumor Invasion and Metastasis by Targeting MYH9 in Human Gastric Cancer

BACKGROUND: MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. METHODOLOGY/PRINCIPAL: Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3'UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis

Translating Technology and Culture: Analysis of Translation of Non-literary Chinese Texts in Science and Civilisation in China

Science and Civilisation in China is needless to say important for understanding and studying China and its technology and culture, but the translation of those technical terms and books has been little systematically discussed. The study, through a self-collected bilingual corpus of culture-loaded texts in those volumes, describes the translation features and explains the translation effects brought by the series of Science and Civilisation in China. It finds out that the book editors tried to keep a balance between literal and free translation by maintaining pinyin spelling in Wade-Giles style in translating those cultural and technical terms, while necessary annotation and abundant illustrations are added. The translations of terms keep good consistency though those various volumes are published over decades. The translated texts constitute a significant part in each volume. The study highlights the important role of translation of non-literary texts in introducing Chinese science and culture. It argues that writing or editing books on Chinese science and technology is also a way of translating China and its civilisation, and therefore calls for academic attention on the translation study of more Chinese non-literary works

Translating Technology and Culture: Analysis of Translation of Non-literary Chinese Texts in Science and Civilisation in China

Science and Civilisation in China is needless to say important for understanding and studying China and its technology and culture, but the translation of those technical terms and books has been little systematically discussed. The study, through a self-collected bilingual corpus of culture-loaded texts in those volumes, describes the translation features and explains the translation effects brought by the series of Science and Civilisation in China. It finds out that the book editors tried to keep a balance between literal and free translation by maintaining pinyin spelling in Wade-Giles style in translating those cultural and technical terms, while necessary annotation and abundant illustrations are added. The translations of terms keep good consistency though those various volumes are published over decades. The translated texts constitute a significant part in each volume. The study highlights the important role of translation of non-literary texts in introducing Chinese science and culture. It argues that writing or editing books on Chinese science and technology is also a way of translating China and its civilisation, and therefore calls for academic attention on the translation study of more Chinese non-literary works

Uniform Convergence and Transitive Subsets

Let (X,d) be a metric space and a sequence of continuous maps fn:X→X that converges uniformly to a map f. We investigate the transitive subsets of fn whether they can be inherited by f or not. We give sufficient conditions such that the limit map f has a transitive subset. In particular, we show the transitive subsets of fn that can be inherited by f if fn converges uniformly strongly to f