Health-related Quality of life in 640 head and neck cancer survivors after radiotherapy using EORTC QLQ-C30 and QLQ-H&N35 questionnaires

<p>Abstract</p> <p>Background</p> <p>With the advances in modern radiotherapy (RT), many patients with head and neck cancer (HNC) can be effectively cured, and their health-related quality of life (HR-QoL) has become an important issue. In this study, we evaluated the prognosticators of HR-QoL in a large cohort of HNC patients, with a focus on the result from technological advances in RT.</p> <p>Methods</p> <p>A cross-sectional investigation was conducted to assess the HR-QoL of 640 HNC patients with cancer-free survival of more than 2 years. Among them, 371 patients were treated by two-dimensional RT (2DRT), 127 by three-dimensional conformal RT (3DCRT), and 142 by intensity-modulated RT (IMRT). The EORTC QLQ-C30 questionnaire and QLQ-H&N35 module were used. A general linear model multivariate analysis of variance was used to analyze the prognosticators of HR-QoL.</p> <p>Results</p> <p>By multivariate analysis, the variables of gender, annual family income, tumor site, AJCC stage, treatment methods, and RT technique were prognosticators for QLQ-C30 results, so were tumor site and RT technique for H&N35. Significant difference (<it>p </it>< 0.05) of HR-QoL outcome by different RT techniques was observed at 2 of the 15 scales in QLQ-C30 and 10 of the 13 scales in H&N35. Compared with 2DRT, IMRT had significant better outcome in the scales of global QoL, physical functioning, swallowing, senses (taste/smell), speech, social eating, social contact, teeth, opening mouth, dry mouth, sticky saliva, and feeling ill.</p> <p>Conclusions</p> <p>The technological advance of RT substantially improves the head-and-neck related symptoms and broad aspects of HR-QoL for HNC survivors.</p

Assessing the Microclimate Effects and Irrigation Water Requirements of Mesic, Oasis, and Xeric Landscapes

Urban irrigation is an essential process in land–atmosphere interactions. It is one of the uncertain parameters of urban hydrology due to various microclimates. This study investigated the microclimate effects and irrigation water requirements of three landscape types in an arid region of Phoenix, AZ. The microclimate effect encompassed surface temperature, air temperature, and wind speed. The simulations of the three landscapes were conducted using ENVI-met software for the hottest day of the year (23 June 2011). The simulated model was validated using ground data. Results show that the mesic landscape induced cooling effects, both in the daytime and nighttime, by reducing surface and air temperatures. However, the mesic landscape showed high-water consumption because of a high leaf area density. The oasis landscape showed 2 °C more daytime cooling than the mesic landscape, but the nighttime warming (surface temperature) was comparable to the xeric landscape. The potential irrigation water requirement was 1 mm/day lower than the mesic landscape. Moreover, microclimate conditions varied spatially in each neighborhood. The xeric landscape showed lower wind speeds and air temperatures between the buildings. The wind speed variations in the three landscapes were inconclusive due to differences in building orientations and discrepancies in trees’ heights. The findings can have implications for restricting the municipal irrigation budget. In addition, they can help water managers in choosing a landscape in urban areas. Urban scientists can adapt the methodology to quantify urban ET in arid regions

Bioactive cyclometalated phthalimides: design, synthesis and kinase inhibition

National Institutes of Health USA [CA114046]; German Research Foundation (DFG); Fonds der Chemischen IndustrieThe regioselective cyclometalation of 4-(pyridin-2-yl)phthalimide was exploited for the economical design of organometallic protein kinase inhibitors. 4-(Pyridin-2-yl)phthalimide can be prepared from inexpensive 4-bromophthalimide in just three steps including one Pd-catalyzed Stille cross-coupling. The versatility of this new ligand was demonstrated with the synthesis of ruthenium(II) half-sandwich as well as octahedral ruthenium(II) and iridium(III) complexes. The regioselectivity of the C-H activation in the course of the cyclometalation can be influenced by the reaction conditions and the steric demand of the introduced metal complex fragment. The biological activity of this new class of metalated phthalimides was evaluated by profiling two representative members against a large panel of human protein kinases. A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site

Rhodium-Catalyzed Enantioselective Addition of Organoaluminum Reagents to <i>N</i>‑Tosyl Ketimines

Rhodium­(I)/Binap complexes catalyze highly enantioselective additions of methyl- and arylaluminum reagents to cyclic α,β-unsaturated <i>N</i>-tosyl ketimines. Depending on the solvent and substituents at the ring, the reaction occurs either in a 1,2-manner to deliver α-tertiary allylic amines or in a 1,4-manner to yield, after subsequent reduction, 3-substituted cycloalkyl amines. Well known in the case of the respective cycloalkenones, these first transformations of the aza-analogues enable the synthesis of amine structures of pharmaceutical and biochemical interest

Self-Assembled Hybrid Aptamer-Fc Conjugates for Targeted Delivery: A Modular Chemoenzymatic Approach

Over the past decade, DNA and RNA aptamers have attracted keen research interest due to their ability to specifically bind targets of therapeutic relevance. However, their application is often hampered by a short serum half-life and missing effector functions. Conjugation of aptamers to antibody Fc fragments could improve pharmacokinetics, enable immune effector mechanisms, and provide an option for the introduction of desired payloads (e.g., toxins or fluorescent dyes). We developed a modular scaffold-supported system based on human IgG1 Fc fragments, which allows for its dual functionalization with moieties of interest. In our approach, two bioorthogonal, enzyme-mediated reactions were used in combination with oxime ligation and self-assembly based on PNA–DNA base pairing. Thus, an engineered synthetic peptide nucleic acid (PNA) oligomer was coupled to the <i>C</i>-termini of the Fc dimer upon sequence-specific sortase A-mediated transpeptidation. Hybridization of the resulting Fc-PNA conjugate with a tailored DNA aptamer that binds cancer-related hepatocyte growth factor receptor (c-MET) led to a hybrid construct which showed strong and specific binding to c-MET and was readily internalized by c-MET-overexpressing cells. To install an additional orthogonally addressable site, aldehyde tag technology was applied followed by oxime ligation with an aminooxy-bearing fluorescent dye as model cargo. Delivery of fluorescent probe specifically to c-MET-overexpressing cells was confirmed by flow cytometry. Our approach can provide access to engineered aptamer-Fc conjugates with desired target specificity and cytotoxic payloads

Digital Object Characterization: Document Conversion and Qualiity Assurance

Whether we are migrating document formats to achieve interoperability or ensure long term preservation, we are faced with the issue of assessing the quality of the digital object transformation. However, comparing two digital objects is not straightforward. It raises the issue of properties that are inherent to the digital objects and those that are dependent on the environment in which the objects are created, viewed, and compared to one another. That has implications for devising methods to extract document properties, interpret observed characteristics, and apply similarity metrics. Furthermore, in order to take actions based on collected measurements, we need to define or learn the significance of individual document properties from the perspective of human perception and usage scenarios. We illustrate the complexity of these issues by presenting a method for comparing converted office documents and discussing the challenges from the technical and methodology point of view