Ictal and interictal MEG in pediatric patients with tuberous sclerosis and drug resistant epilepsy

Purpose: Drug resistant epilepsy (DRE) is common in patients with tuberous sclerosis (TS). Interictal MEG has been shown as a valuable instrument in the presurgical workup. The goal of our study was to evaluate the role of ictal MEG in epileptogenic tuber selection, especially in patients with multiple irritative zones. Methods: The clinical and MEG data of 23 patients with TS and DRE from two medical/research centers were reviewed. Seven pediatric patients, who had seizures during MEG recording and underwent resection or disconnection surgery, were included into the study. Cortical sources of ictal and interictal epileptiform MEG discharges were compared with epileptogenic zone location in six patients with favorable surgery outcome. Results: In patients who improved substantially after surgery all resected and several other tubers demonstrated epileptiform activity on interictal MEG. Ictal MEG provided crucial information about lobar location of the seizure onset zone (SOZ) in two cases, and in the other four it confirmed the SOZ location derived from the interictal data. In one case, ictal MEG findings were unreliable. In one patient, who did not benefit from surgical treatment, the resected tubers did not overlap with interictal and ictal MEG sources. Conclusion: The combination of interictal and ictal MEG is a valuable tool for identification of the epileptogenic tuber/tubers in presurgical work-up in patients with TS.Peer reviewe

Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation.Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic "sugar" cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic "sugar" cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress.Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed

Algorithmic Aspects of Heterogeneous Biological Networks Comparison ⋆

Abstract. Biological networks are commonly used to model molecular activity within the cell. Recent experimental studies have shown that the detection of conserved subnetworks across several networks, coming from different organisms, may allow the discovery of disease pathways and prediction of protein functions. There already exist automatic methods that allow to search for conserved subnetworks using networks alignment; unfortunately, these methods are limited to networks of same type, thus having the same graph representation. Towards overcoming this limitation, a unified framework for pairwise comparison and analysis of networks with different graph representations (in particular, a directed acyclic graph D and an undirected graph G over the same set of vertices) is presented in [4]. We consider here a related problem called k-DAGCC: given a directed graph D and an undirected graph G on the same set V of vertices, and an integer k, does there exist sets of vertices V1, V2,... Vk ′, k ′ ≤ k such that, for each 1 ≤ i ≤ k ′ , (i) D[Vi] is a DAG and (ii) G[Vi] is connected? Two variants of k-DAGCC are of interest: (a) the Vis must form a partition of V, or (b) the Vis must form a cover of V. We study the computational complexity of both variants of k-DAGCC and, depending on the constraints imposed on the input, provide several polynomial-time algorithms, hardness and inapproximability results.