Reliability of Clinician-Based (GRBAS and CAPE-V) and Patient-Based (V-RQOL and IPVI) Documentation of Voice Disorders

This study examined the reliability of two methods for documenting voice quality by clinicians and compared the methods for documenting patients' perceptions of voice quality. It involved a prospective reliability study and a retrospective chart review. Reliability of two clinician-based voice assessment protocols-Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) and Consensus Auditory Perceptual Evaluation-Voice (CAPE-V)-was evaluated. These two protocols were then compared after use in voice assessments of 42 males and 61 females performed by a certified speech-language pathologist specializing in the assessment of voice disorders. In addition, two patient-based scales (Voice Related Quality of Life, or V-RQOL, and Iowa Patient's Voice Index, or IPVI) obtained from the same patients were compared with each other and with the clinician-based scales. Reliability of clinicians' ratings of overall severity of dysphonia using GRBAS and CAPE-V scales was very good (r>0.80). Agreement between V-RQOL Total scores and IPVI ratings of the patient's perceptions of impact of dysphonia was less strong (Spearman's r=-0.76). There was relatively weak agreement between patient-based and clinician-based scales. Clinician's perceptions of dysphonia appeared to be reliable and unaffected by rating tool, as indicated by the high level of agreement between the two rating systems when they were used together. The CAPE-V system appeared to be more sensitive to small differences within and among patients than the GRBAS system. The V-RQOL and IPVI approaches to documenting patient's perceptions of dysphonia agreed less well possibly due to differences in patient dependence on voice and on interpretation of the rating tool items. The differences between clinician-based and patient-based data support the conclusion that clinicians and patients experience and consider dysphonia very differently.     

Distinct Mechanisms of Cytotoxicity in Novel Nitrogenous Heterocycles: Future Directions for a New Anti-Cancer Agent

Electron-rich, nitrogenous heteroaromatic compounds interact more with biological/cellular components than their non-nitrogenous counterparts. The strong intermolecular interactions with proteins, enzymes, and receptors confer significant biological and therapeutic properties to the imidazole derivatives, giving rise to a well-known and extensively used range of therapeutic drugs used for infections, inflammation, and cancer, to name a few. The current study investigates the anti-cancer properties of fourteen previously synthesized nitrogenous heterocycles, derivatives of imidazole and oxazolone, on a panel of cancer cell lines and, in addition, predicts the molecular interactions, pharmacokinetic and safety profiles of these compounds. Method: The MTT and CellTiter-Glo^® assays were used to screen the imidazole and oxazolone derivatives on six cancer cell lines: HL60, MDA-MB-321, KAIMRC1, KMIRC2, MCF-10A, and HCT8. Subsequently, in vitro tubulin staining and imaging were performed, and the level of apoptosis was measured using the Promega ApoTox-Glo^® triplex assay. Furthermore, several computational tools were utilized to investigate the pharmacokinetics and safety profile, including PASS Online, SEA Search, the QikProp tool, SwissADME, ProTox-II, and an in silico molecular docking study on tubulin to identify the critical molecular interactions. Results: In vitro analysis identified compounds 8 and 9 to possess the most significant potent cytotoxic activity on the HL60 and MDA-MB-231 cell lines, supported by PASS Online anti-cancer predictions with pa scores of 0.413 and 0.434, respectively. In addition, compound 9 induced caspase 3/7 dependent-apoptosis and interfered with tubulin polymerization in the MDA-MB-231 cell line, consistent with in silico docking results, identifying binding similarity to the native ligand colchicine. All the derivatives, including compounds 8 and 9, had acceptable pharmacokinetics; however, the safety profile was suboptimal for all the tested derivates except compound 4. Conclusion: The imidazole derivative compound 9 is a promising anti-cancer agent that switches on caspase-dependent apoptotic cell death and modulates microtubule function. Therefore, it could be a lead compound for further drug optimization and development.     

Axonal Buckling Following Stretch Injury

Diffuse brain injury is caused by rapid rotation of the head, and causes strain injury to tissue throughout the brain. Following strain injury, axons exhibit delayed recovery, showing regional buckling behavior immediately after stretch and returning to their original appearance over an extended period of time. This axonal buckling is hypothesized to occur as a result of localized stretching within the axon: Rapid strain causes mechanical damage to microtubules, increasing the effective length of axons. This damage is repaired gradually returning the axon to its initial length.Here, we test the hypothesis that localized stretching is a possible explanation for the regional buckling behavior. An elongated region of axon is modeled as an Euler beam on an elastic foundation, where the foundation represents the surrounding brain tissue, which consists of glial cells and extracellular matrix. After stretch the elastic foundation returns immediately to its pre-stretch length, while the axon is initially elongated and returns to its original length over a longer period of time. The model exhibits solutions similar to those observed experimentally in post-stretch axons, with undulations that have a similar wavelength and amplitude.     

Ab initio study of cationic polymeric membranes in water and methanol

The work is devoted to a computational study of three types of cationic polymeric membranes in Li⁺-ionic form, in water and methanol environments, at various solvation levels. The studied membranes Nafion, IonClad, and M3 possess the perfluorinated backbone; however, various side chains were terminated with the functional groups of distinctly different ionic strength. The paper discusses the structural features of the membrane-solvent clusters as well as an influence of the side chain nature on the dissociation of the functional groups and the binding energy of the solvent molecules. Additionally, the paper compares the obtained results for Li⁺-Nafion membrane in water with the results published earlier for H⁺ and Na⁺ forms.     

Microwave-assisted synthesis and electrochemical characterization of α-MnO2 as catalyst for lithium-air batteries

A novel preparation path for the synthesis of MnO₂-based wire-shaped catalyst material for lithium-air electrodes is presented. The electrode was prepared with direct laser-transfer, which is solvent free and considered environmental benign. High specific charge, 869 and 2978 A h kg^?1, was achieved for the total mass of one electrode and carbon content, respectively. The electrode faded about 11% of the initial specific charge after 60 cycles.     

Palladium‐Catalyzed Chemoselective and Biocompatible Functionalization of Cysteine‐Containing Molecules at Room Temperature

The third generation of aminobiphenyl palladacycle pre‐catalyst “G3‐Xantphos” enables functionalization of peptides containing cysteine in high yields. The conjugation (bioconjugation) occurs chemoselectively at room temperature under biocompatible conditions. Extension of the method to protein functionalization allows selective bioconjugation of the trastuzumab antibody.     

A dispersive liquid–liquid micellar microextraction for the determination of pharmaceutical compounds in wastewaters using ultra‐high‐performace liquid chromatography with DAD detection

A dispersive liquid–liquid micellar microextraction (DLLMME) method coupled with ultra‐high‐performance liquid chromatography (UHPLC) using Diode Array Detector (DAD) detector was developed for the analysis of five pharmaceutical compounds of different nature in wastewaters. A micellar solution of a surfactant, polidocanol, as extraction solvent (100 μL) and chloroform as dispersive solvent (200 μL) were used to extract and preconcentrate the target analytes. Samples were heated above critical temperature and the cloudy solution was centrifuged. After removing the chloroform, the reduced volume of surfactant was then injected in the UHPLC system. In order to obtain high extraction efficiency, the parameters affecting the liquid‐phase microextraction, such as time and temperature extraction, ionic strength and surfactant and organic solvent volume, were optimized using an experimental design. Under the optimized conditions, this procedure allows enrichment factors of up to 47‐fold. The detection limit of the method ranged from 0.1 to 2.0 µg/L for the different pharmaceuticals. Relative standard deviations were <26% for all compounds. The procedure was applied to samples from final effluent collected from wastewater treatment plants in Las Palmas de Gran Canaria (Spain), and two compounds were measured at 67 and 113 µg/L in one of them. Copyright © 2014 John Wiley & Sons, Ltd.