Quinidine: an “Endangered Species” Drug Appropriate for Management of Electrical Storm in Brugada Syndrome

Brugada syndrome is an inherited channelopathy associated with an increased risk of syncope and sudden cardiac death. In rare cases it can be manifested with electrical storm. We report two cases of Brugada syndrome that presented with electrical storm and were treated successfully with oral quinidine, an "endangered species" drug.     

Risk-Adjusted Control Charts: Theory,Methods, and Applications in Health

Control charts, the most popular tool of statistical process control, appeared in the literature to ensure that an industrial process is operating only with natural variability, i.e., under statistical control. In the last decades, control charts have been also widely used to assess the quality of non-industrial processes, such as medicine and public health. Mainly in the last two decades, a modification of standard and advanced control charts appeared in the bibliography to improve the monitoring mainly of medical processes. This is the risk-adjusted control charts which take into consideration the varying health conditions of the patients. These charts are used to monitor certain medical processes such as surgeries, mortality, and doctors’ experience. In this paper, we have tried to present all the risk-adjusted control charts presented in the literature appropriately categorized. The risk-adjusted charts have been grouped into three categories: control charts for continuous variables, control charts for attributes (non-continuous variables), time-weighted control charts. The application of risk-adjusted control charts in practical medical processes is also discussed. This review paper highlights the value of the risk-adjusted control charts.

     

Bundle sheath extensions affect leaf structural and physiological plasticity in response to irradiance

Coordination between structural and physiological traits is key to plants' responses to environmental fluctuations. In heterobaric leaves, bundle sheath extensions (BSEs) increase photosynthetic performance (light‐saturated rates of photosynthesis, A_max) and water transport capacity (leaf hydraulic conductance, K_leaf). However, it is not clear how BSEs affect these and other leaf developmental and physiological parameters in response to environmental conditions. The obscuravenosa (obv) mutation, found in many commercial tomato varieties, leads to absence of BSEs. We examined structural and physiological traits of tomato heterobaric and homobaric (obv) near‐isogenic lines grown at two different irradiance levels. K_leaf, minor vein density, and stomatal pore area index decreased with shading in heterobaric but not in homobaric leaves, which show similarly lower values in both conditions. Homobaric plants, on the other hand, showed increased A_max, leaf intercellular air spaces, and mesophyll surface area exposed to intercellular airspace (S_mes) in comparison with heterobaric plants when both were grown in the shade. BSEs further affected carbon isotope discrimination, a proxy for long‐term water‐use efficiency. BSEs confer plasticity in traits related to leaf structure and function in response to irradiance levels and might act as a hub integrating leaf structure, photosynthetic function, and water supply and demand.     

Titanium with nanotopography induces osteoblast differentiation through regulation of integrin αV

Topographical modifications of titanium (Ti) at the nanoscale level generate surfaces that regulate several signaling pathways and cellular functions, which may affect the process of osseointegration. Here, we investigated the participation of integrin αV in the osteogenic capacity of Ti with nanotopography. Machined titanium discs (untreated) were submitted to treatment with H₂SO₄/H₂O₂ to produce the nanotopography (nanostructured). First, the greater osteogenic capacity of the nanotopography that increased osteoblast differentiation of mesenchymal stem cells compared with untreated topography was shown. Also, the nanostructured surface increased (regulation ≥ 1.9-fold) the gene expression of 6 integrins from a custom array plate utilized to evaluate the gene expression of 84 genes correlated with cell adhesion signaling pathway, including integrin αV, which is involved in osteoblast differentiation. By silencing integrin αV in MC3T3-E1 cells cultured on nanotopography, the impairment of osteoblast differentiation induced by this surface was observed. In conclusion, it was shown that nanotopography regulates the expression of several components of the cell adhesion signaling pathway and its higher osteogenic potential is, at least in part, due to its ability to upregulate the expression of integrin αV. Together with previous data that showed the participation of integrins α1, β1, and β3 in the nanotopography osseoinduction activity, we have uncovered the pivotal role of this family of membrane receptors in the osteogenic potential of this surface.     

Brain mechanics For neurosurgery: modeling issues

 Brain biomechanics has been investigated for more than 30 years. In particular, finite element analyses and other powerful computational methods have long been used to provide quantitative results in the investigation of dynamic processes such as head trauma. Nevertheless, the potential of these methods to simulate and predict the outcome of quasi-static processes such as neurosurgical procedures and neuropathological processes has only recently been explored. Some inherent difficulties in modeling brain tissues, which have impeded progress, are discussed in this work. The behavior of viscoelastic and poroelastic constitutive models is compared in simple 1-D simulations using the ABAQUS finite element platform. In addition, the behaviors of quasi-static brain constitutive models that have recently been proposed are compared. We conclude that a compressible viscoelastic solid model may be the most appropriate for modeling neurosurgical procedures. Received: 19 March 2002 / Accepted: 6 June 2002 Work is supported by a generous grant from the Whitaker Foundation. We would like to also thank Dr. Christos Davatzikos (Johns Hopkins School of Medicine, Baltimore, Maryland) for his help.     

Topographical Estimation of Visual Population Receptive Fields by fMRI

Visual cortex is retinotopically organized so that neighboring populations of cells map to neighboring parts of the visual field. Functional magnetic resonance imaging allows us to estimate voxel-based population receptive fields (pRF), i.e., the part of the visual field that activates the cells within each voxel. Prior, direct, pRF estimation methods¹ suffer from certain limitations: 1) the pRF model is chosen a-priori and may not fully capture the actual pRF shape, and 2) pRF centers are prone to mislocalization near the border of the stimulus space. Here a new topographical pRF estimation method² is proposed that largely circumvents these limitations. A linear model is used to predict the Blood Oxygen Level-Dependent (BOLD) signal by convolving the linear response of the pRF to the visual stimulus with the canonical hemodynamic response function. PRF topography is represented as a weight vector whose components represent the strength of the aggregate response of voxel neurons to stimuli presented at different visual field locations. The resulting linear equations can be solved for the pRF weight vector using ridge regression³, yielding the pRF topography. A pRF model that is matched to the estimated topography can then be chosen post-hoc, thereby improving the estimates of pRF parameters such as pRF-center location, pRF orientation, size, etc. Having the pRF topography available also allows the visual verification of pRF parameter estimates allowing the extraction of various pRF properties without having to make a-priori assumptions about the pRF structure. This approach promises to be particularly useful for investigating the pRF organization of patients with disorders of the visual system.     

Bombesin and neurotensin exert antiproliferative effects on oval cells and augment the regenerative response of the cholestatic rat liver

The regenerative capacity of the cholestatic liver is significantly attenuated. Oval cells are hepatic stem cells involved in liver's regeneration following diverse types of injury. The present study investigated the effect of the neuropeptides bombesin (BBS) and neurotensin (NT) on oval cell proliferation as well as on hepatocyte and cholangiocyte proliferation and apoptosis in the cholestatic rat liver. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (30 μg/kg/d), BDL + NT (300 μg/kg/d). Ten days later, alpha-fetoprotein (AFP) mRNA (in situ hybridization), cytokeratin-19 and Ki67 antigen expression (immunohistochemistry) and apoptosis (TUNEL) were evaluated on liver tissue samples. Cells with morphologic features of oval cells that were cytokeratin-19(+) and AFP mRNA(+) were scored in morphometric analysis and their proliferation was recorded. In addition, the proliferation and apoptotic rates of hepatocytes and cholangiocytes were determined. Alanine aminotransferase (ALT) levels and hepatic oxidative stress (lipid peroxidation and glutathione redox state) were also estimated. The neuropeptides BBS and NT significantly reduced ALT levels and hepatic oxidative stress. Both agents exerted similar and cell type-specific effects on oval cells, hepatocytes and cholangiocytes: (a) oval cell proliferation and accumulation in the cholestatic liver was attenuated, (b) hepatocyte proliferation was increased along with a decreased rate of their apoptosis and (c) cholangiocyte proliferation was attenuated and their apoptosis was increased. These observations might be of potential value in patients with extrahepatic cholestasis.     

Interaction of aminoadamantane derivatives with the influenza A virus M2 channel-Docking using a pore blocking model

Interaction of aminoadamantanes with the influenza A virus M2 proton channel was analyzed by docking simulations of a series of synthetic aminoadamantane derivatives, of differing binding affinity, into the crystal structure of the transmembrane (M2TM) pore. The pore blocking model tested in the ‘gas phase’ describes qualitatively the changes on the relative binding affinities of the compounds (although a series of highly hydrophobic ligands which seem to have little capacity for different specific interactions with their receptor). The docking calculations predicted poses in which the adamantane ring is surrounded mainly by the alkyl side chains of Val27 or Ala30 and the ligand’s amino group is generally hydrogen bonded with hydroxyls of Ser31 or carbonyls of Val27 or carbonyls of Ala30, the former (Ser31) being the most stable and most frequently observed. The binding of the ligand is a compromise between hydrogen bonding ability, which is elevated by a primary amino group, and apolar interactions, which are increased by the ability of the lipophilic moiety to adequately fill a hydrophobic pocket within the M2TM pore. A delicate balance of these hydrophobic contributions is required for optimal interaction.