Review of Levetiracetam as a First Line Treatment in Status Epilepticus in the Adult Patients – What Do We Know so Far?

With the advent of new antiepileptic drugs comes the potential for significant advances in the emergent management of status epilepticus. Traditional antiepileptic drugs possess side effect profiles that may limit their clinical utility or lead to increased patient morbidity or mortality. The relatively recent development of levetiracetam shows promise for effective control of acute status epilepticus in adults, but current objective data of its use as a first-line agent for control of status is quite limited. This paper serves to examine existing literature while considering levetiracetam as a first-line therapy in status in the adult patient population. Although existing studies are narrow in their scope, the present data lay a substantial foundation for further investigation of levetiracetam as a primary therapy in acute status epilepticus

Different Modulation of the Cortical Silent Period by Two Phases of Short Interval Intracortical Inhibition

PURPOSE: To investigate the influence of 2 phases of short interval intracortical inhibition (SICI) on the cortical silent period (SP). MATERIALS AND METHODS: Single- and paired-pulse transcranial magnetic stimulations (TMSs) at 1 and 2.5ms interstimulus intervals (ISIs) were applied to the left motor cortex in 12 healthy subjects while their right hand muscles were moderately activated. Conditioning stimulation intensity was 90% of the active motor threshold (AMT). Test stimulation intensities were 120, 140, 160, 180, 200, 220, 240, 260% of the AMT and at 100% of the maximal stimulator output, the order of which was arranged randomly. The rectified electromyography area of motor evoked potential (MEP) and duration of the SP were measured off-line using a computerized program. RESULTS: At high-test stimulation intensities, MEP areas were saturated in both single- and paired-pulse stimulations, except that saturated MEPs were smaller for the paired-pulse TMS at 1ms ISI than for the other conditions. As the test stimulation intensity increased, SP was progressively prolonged in both single- and paired-pulse stimulations but was shorter in paired-pulse than single-pulse TMS. Overall, the ratio of SP duration/MEP area was comparable between single- and paired-pulse TMS except for the paired-pulse TMS at 1 ms ISI with a test stimulation intensity at 140-180% of the AMT, in which the ratio was significantly higher than in the single pulse TMS. CONCLUSION: These results suggest that 2 phases of SICI modulate MEP saturation and SP duration differently and provide additional evidence supporting the view that 2 phases of SICI are mediated by different inhibitory mechanisms.ope

Recent Updates on Acquired Hepatocerebral Degeneration

Background: Acquired hepatocerebral degeneration (AHD) refers to a chronic neurological syndrome in patients with advanced hepatobiliary diseases. This comprehensive review focuses on the pathomechanism and neuroimaging findings in AHD. Methods: A PubMed search was performed using the terms “acquired hepatocerebral degeneration,” “chronic hepatocerebral degeneration,” “Non-Wilsonian hepatocerebral degeneration,” “cirrhosis-related parkinsonism,” and “manganese and liver disease.” Results: Multiple mechanisms involving the accumulation of toxic substances such as ammonia or manganese and neuroinflammation may lead to widespread neurodegeneration in AHD. Clinical characteristics include movement disorders, mainly parkinsonism and ataxia-plus syndrome, as well as cognitive impairment with psychiatric features. Neuroimaging studies of AHD with parkinsonism show hyperintensity in the bilateral globus pallidus on T1-weighted magnetic resonance images, whereas molecular imaging of the presynaptic dopaminergic system shows variable findings. Ataxia-plus syndrome in AHD may demonstrate high-signal lesions in the middle cerebellar peduncles on T2-weighted images. Discussion: Future studies are needed to elucidate the exact pathomechanism and neuroimaging findings of this heterogeneous syndrome

Reconstruction of 7T-Like Images From 3T MRI

In the recent MRI scanning, ultra-high-field (7T) MR imaging provides higher resolution and better tissue contrast compared to routine 3T MRI, which may help in more accurate and early brain diseases diagnosis. However, currently, 7T MRI scanners are more expensive and less available at clinical and research centers. These motivate us to propose a method for the reconstruction of images close to the quality of 7T MRI, called 7T-like images, from 3T MRI, to improve the quality in terms of resolution and contrast. By doing so, the post-processing tasks, such as tissue segmentation, can be done more accurately and brain tissues details can be seen with higher resolution and contrast. To do this, we have acquired a unique dataset which includes paired 3T and 7T images scanned from same subjects, and then propose a hierarchical reconstruction based on group sparsity in a novel multi-level Canonical Correlation Analysis (CCA) space, to improve the quality of 3T MR image to be 7T-like MRI. First, overlapping patches are extracted from the input 3T MR image. Then, by extracting the most similar patches from all the aligned 3T and 7T images in the training set, the paired 3T and 7T dictionaries are constructed for each patch. It is worth noting that, for the training, we use pairs of 3T and 7T MR images from each training subject. Then, we propose multi-level CCA to map the paired 3T and 7T patch sets to a common space to increase their correlations. In such space, each input 3T MRI patch is sparsely represented by the 3T dictionary and then the obtained sparse coefficients are used together with the corresponding 7T dictionary to reconstruct the 7T-like patch. Also, to have the structural consistency between adjacent patches, the group sparsity is employed. This reconstruction is performed with changing patch sizes in a hierarchical framework. Experiments have been done using 13 subjects with both 3T and 7T MR images. The results show that our method outperforms previous methods and is able to recover better structural details. Also, to place our proposed method in a medical application context, we evaluated the influence of post-processing methods such as brain tissue segmentation on the reconstructed 7T-like MR images. Results show that our 7T-like images lead to higher accuracy in segmentation of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and skull, compared to segmentation of 3T MR images

A short review: Recent advances in electrospinning for bone tissue regeneration

Nanofibrous structures developed by electrospinning technology provide attractive extracellular matrix conditions for the anchorage, migration, and differentiation of tissue cells, including those responsible for the regeneration of hard tissues. Together with the ease of set up and cost-effectiveness, the possibility to produce nanofibers with a wide range of compositions and morphologies is the merit of electrospinning. Significant efforts have exploited the development of bone regenerative nanofibers, which includes tailoring of composite/hybrid compositions that are bone mimicking and the surface functionalization such as mineralization. Moreover, by utilizing bioactive molecules such as adhesive proteins, growth factors, and chemical drugs, in concert with the nanofibrous matrices, it is possible to provide artificial materials with improved cellular responses and therapeutic efficacy. These studies have mainly focused on the regulation of stem cell behaviors for use in regenerative medicine and tissue engineering. While there are some challenges in achieving controllable delivery of bioactive molecules and complex-shaped three-dimensional scaffolds for tissue engineering, the electrospun nanofibrous matrices can still have a beneficial impact in the area of hard-tissue regeneration

Effects on Growth and Osteogenic Differentiation of Mesenchymal Stem Cells by the Zinc-Added Sol-Gel Bioactive Glass Granules

Responses of mesenchymal stem cells (MSCs) cultured with zinc-added (2 and 5%) bioactive glass granules were evaluated in terms of cell growth and osteogenic differentiation. MSCs were cultured with different quantities (3, 10 and 30) of glass granules for up to 21 days in the osteogenic medium. Cell growth was stimulated by a small quantity of glasses, particularly those that contained zinc. Osteogenic differentiation, as assessed by alkaline phosphatase activity (ALP) activity, was significantly enhanced by the glasses, particularly with large quantities of glass and for prolonged culturing. Expression of bone-sialo protein (BSP) was significantly up-regulated around the bioactive glass granules. Moreover, the zinc addition significantly altered the ALP and BSP depending on the culture time and glass quantity. Cellular mineralization was improved in all glass samples, and particularly in the 2% zinc-glass. Taken together, the zinc addition to bioactive glass induced the MSCs growth and their osteogenic differentiation, at least to the level of zinc-free glass, and with even higher level observed depending on the quantity and culture time. These findings indicate that the zinc addition to bioactive glass may be useful in development of biomaterials for the stimulation of adult stem cell in bone tissue engineering

Carbon Nanotubes in Nanocomposites and Hybrids with Hydroxyapatite for Bone Replacements

Hydroxyapatite (HA), as a bone mineral component, has been an attractive bioceramic for the reconstruction of hard tissues. However, its poor mechanical properties, including low fracture toughness and tensile strength, have been a significant challenge to the application of HA for the replacement of load-bearing and/or large bone defects. Among materials studied to reinforce HA, carbon nanotubes (CNTs: single-walled or multiwalled) have recently gained significant attention because of their unprecedented mechanical properties (high strength and toughness) and physicochemical properties (high surface area, electrical and thermal conductivity, and low weight). Here, we review recent studies of the organization of HA-CNTs at the nanoscale, with a particular emphasis on the functionalization of CNTs and their dispersion within an HA matrix and induction of HA mineralization. The organization of CNTs and HA implemented at the nanoscale can further be developed in the form of coatings, nanocomposites, and hybrid powders to enable potential applications in hard tissue reconstruction

Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent

Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms

High-resolution crystal structure of the non-specific lipid-transfer protein from maize seedlings

AbstractBackground: The movement of lipids between membranes is aided by lipid-transfer proteins (LTPs). Some LTPs exhibit broad specificity, transferring many classes of lipids, and are termed non-specific LTPs (ns-LTPs). Despite their apparently similar mode of action, no sequence homology exists between mammalian and plant ns-LTPs and no three-dimensional structure has been reported for any plant ns-LTP.Results We have determined the crystal structure of ns-LTP from maize seedlings by multiple isomorphous replacement and refined the structure to 1.9 å resolution. The protein comprises a single compact domain with four α-helices and a long C-terminal region. The eight conserved cysteines form four disulfide bridges (assigned as Cys4–Cys52, Cys14–Cys29, Cys30–Cys75, and Cys50–Cys89) resolving the ambiguity that remained from the chemical determination of pairings in the homologous protein from castor bean. Two of the bonds, Cys4–Cys52 and Cys50–Cys89, differ from what would have been predicted from sequence alignment with soybean hydrophobic protein. The complex between maize ns-LTP and hexadecanoate (palmitate) has also been crystallized and its structure refined to 1.8 å resolution.Conclusion The fold of maize ns-LTP places it in a new category of all-α-type structure, first described for soybean hydrophobic protein. In the absence of a bound ligand, the protein has a tunnel-like hydrophobic cavity, which is large enough to accommodate a long fatty acyl chain. In the structure of the complex with palmitate, most of the acyl chain is buried inside this hydrophobic cavity