Gap filling strategies for 3-D-FBP reconstructions of High-Resolution Research Tomograph scans

The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography scanner. Currently available iterative reconstruction algorithms show bias due to nonnegativity constraints. Consequently, implementation of 3-D filtered backprojection (3-D-FBP) is of interest. To apply 3-D-FBP all missing data including those due to gaps between detector heads need to be estimated. The aim of this study was to evaluate various gap filling strategies for 3-D-FBP reconstructions of HRRT data, such as linear and bilinear interpolation or constraint Fourier space gap filling (confosp). Furthermore, missing planes were estimated using segment 0 image data only (noniterative) or by using reconstructed images based on all previous segments (iterative method). Use of bilinear interpolation showed worst correspondence between reconstructed and true activity concentration, especially for small structures. Moreover, phantom data indicated that use of linear interpolation resulted in artifacts in planes located near the edge of the field-of-view. Use of confosp did not show these artifacts. Iterative estimations of the missing planes for $vert {hbox {segments}}vert > 0$ improved image quality at the cost of more computation time. Therefore, use of confosp for filling sinogram gaps with both iterative and noniterative estimation of missing planes are recommended for quantitative 3-D-FBP of HRRT studies.      

Comparison of the new acceleration spectrum analysis with other time- and frequency-domain analyses of the signal-averaged electrocardiogram

AIM: To compare four analysis techniques of the signal-averaged-electrocardiogram, including time-domain, spectral temporal mapping, spectral turbulence analysis and the new acceleration spectrum analysis. METHODS AND RESULTS: We studied 634 subjects (77 with bundle branch block) divided into three groups. Group 1 comprised 117 post-myocardial infarction patients tested for inducibility of sustained ventricular tachycardia, and which was induced in 54 of them. Group 2 comprised 407 consecutive acute myocardial infarction survivors, followed for 1 year; 29 of them had suffered major arrhythmic events: 15 were cases of sustained ventricular tachycardia, three resuscitated ventricular fibrillation and 11 sudden cardiac death. Group 3 comprised 110 control subjects. The different analysis techniques were compared by their likelihood ratio for the prediction of ventricular tachycardia inducibility (Group 1) or major arrhythmic events (Group 2). The likelihood ratios of spectral-turbulence-analysis, acceleration spectrum analysis, spectral temporal mapping and time-domain were 8.0, 3.3, 1.7, 1.3 in Group 1, and 3.8, 2.1, 1.5, 2.6, in Group 2, while the corresponding false-positive rates in Group 3 (control) were 0.9%, 10.0%, 4.5%, and 3.6%, respectively. CONCLUSION: Spectral turbulence analysis was the most accurate technique for the prediction of either ventricular tachycardia inducibility or major arrhythmic events after myocardial infarction. It also showed the highest specificity among control subjects.     

SIG-1451, a Novel,Non-Steroidal Anti-Inflammatory Compound,Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.     

Cl K-edge X-ray spectroscopic investigation of enzymatic formation of organochlorines in weathering plant material

The contribution of halocarbons from plant weathering to the total organohalogen budget of terrestrial systems is gaining recognition. To evaluate the formation of such halocarbons, speciation of chlorine in Sequoia sempervirens (redwood) needles was examined in the presence of an external chloroperoxidase (CPO) enzyme using Cl K-edge X-ray absorption spectroscopy. The Cl forms in fresh and naturally weathered needles and in model laboratory reactions were compared. To provide a straightforward analogue to the enzymatic chlorination in plants, chlorination reactions were conducted for phenol, a common moiety of plant macromolecules. Plant material chlorination was also examined in the presence of hypochlorite in an ancillary mechanistic investigation. The dominant form of Cl in fresh, unreacted plant material was found to be inorganic Cl-, which was partially converted to organochlorine in the presence of CPO. Chlorination is affected by the nature of reactant (CPO, H2O2) addition, reaction time, and temperature. The organochlorines produced in these laboratory investigations closely resemble those produced during the natural weathering of redwood needles. A striking consistency in chlorine speciation observed among the various sample types suggests that (i) CPO produced by terrestrial organisms could play a vital role in the generation of organochlorines associated with the degradation of plant material and (ii) initial targets of enzymatic chlorination might include lignin-like macromolecules rich in aromatic character and hydroxyl groups. These findings lend further credibility to a significant biogenic contribution to the global organohalogen burden by elucidating a probable route of enzymatic chlorination of natural organic matter in terrestrial systems.     

Chemical modification of poly(epichlorohydrin) with unsaturated potassium carboxylates

Poly(epichlorohydrin) was modified by nucleophilic substitution with some aliphatic potassium carboxylates containing terminal double bonds (10-undecenoate, 4-pentenoate and 3-butenoate). In order to monitor the degree of substitution achieved, different reaction conditions were tested. The polyethers obtained were characterized by spectroscopic techniques, elemental analysis, thermal methods, viscosity determinations and osmometric measurements. A slight crosslinking and the reported main chain cleavage were both detected. Finally, it must be pointed out that, during the substitution reaction with the vinylacetate, isomerization to crotonic ester took place.     

Molecular Changes in Relation to Alcohol Consumption and Hepatocellular Carcinoma

Alcohol is the one of the major causes of liver diseases and promotes liver cirrhosis and hepatocellular carcinoma (HCC). In hepatocytes, alcohol is converted to acetaldehyde, which causes hepatic steatosis, cellular apoptosis, endoplasmic reticulum stress, peroxidation, production of cytokines and reduces immune surveillance. Endotoxin and lipopolysaccharide produced from intestinal bacteria also enhance the production of cytokines. The development of hepatic fibrosis and the occurrence of HCC are induced by these alcohol metabolites. Several host genetic factors have recently been identified in this process. Here, we reviewed the molecular mechanism associated with HCC in alcoholic liver disease.     

CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson’s and Alzheimer’s diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ^●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor–ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.     

Mechanisms of Radical Formation on Chemically Modified Graphene Oxide under Near Infrared Irradiation

In this work, the mechanisms of radical generation on different functionalized graphene oxide (GO) conjugates under near-infrared (NIR) light irradiation are investigated. The GO conjugates are designed to understand how chemical functionalization can influence the generation of radicals. Both pristine and functionalized GO are irradiated by a NIR laser, and the production of different reactive oxygen species (ROS) is investigated using fluorimetry and electron paramagnetic resonance to describe the type of radicals present on the surface of GO. The mechanism of ROS formation involves a charge transfer from the material to the oxygen present in the media, via the production of superoxide and singlet oxygen. Cytotoxicity and effects of ROS generation are then evaluated using breast cancer cells, evidencing a concentration dependent cell death associated to the heat and ROS. The study provides new hints to understand the photogeneration of radicals on the surface of GO upon near infrared irradiation, as well as, to assess the impact on these radicals in the context of a combined drug delivery system and phototherapeutic approach. These discoveries open the way for a better control of phototherapy-based treatments employing graphene-based materials.