Muscle wasting and survival following pre-operative chemoradiotherapy for locally advanced rectal carcinoma

Background & aims: Neoadjuvant chemoradiotherapy (NACRT) has increased local control in locally advanced rectal cancer. Reduced skeletal muscle mass (sarcopenia), or ongoing muscle wasting, is associated with decreased survival in cancer. This study aims to assess the change in body composition during NACRT and its impact on outcome using computed tomography (CT) imaging in locally advancedrectal cancer (LARC) patients. Methods: LARC patients treated with NACRT were selected from a prospectively maintained database and retrospectively analyzed. One-hundred twenty-two patients who received treatment between 2004 and 2012 with available diagnostic CT imaging obtained before and after NACRT were identified. Cross-sectional areas for skeletal muscle was determined, and subsequently normalized for patient height. Differences between skeletal muscle areas before and after NACRT were computed, and their influenceon overall and disease-free survival was assessed. Results: A wide distribution in change of body composition was observed. Loss of skeletal muscle mass during chemoradiotherapy was independently associated with disease-free survival (HR0.971; 95% CI:0.946e0.996; p¼0.025) and distant metastasis-free survival (HR0.942; 95% CI: 0.898e0.988; p¼0.013).No relation was observed with overall survival in the current cohort. Conclusions:Loss of skeletal muscle mass during NACRT in rectal cancer patients is an independent prognostic factor for disease-free survival and distant metastasis-free survival following curative intentresection

Changed Properties of the Cytoplasmic Matrix Associated with Desiccation Tolerance of Dried Carrot Somatic Embryos. An in Situ Fourier Transform Infrared Spectroscopic Study

Abscisic acid-pretreated carrot (Daucus carota) somatic embryos survive dehydration upon slow drying, but fast drying leads to poor survival of the embryos. To determine whether the acquisition of desiccation tolerance is associated with changes in the physical stability of the cytoplasm, in situ Fourier transform infrared microspectroscopy was used. Although protein denaturation temperatures were similar in the embryos after slow or fast drying, the extent of the denaturation was greater after fast drying. Slowly dried embryos are in a glassy state at room temperature, and no clearly defined glassy matrix was observed in the rapidly dried embryos. At room temperature the average strength of hydrogen bonding was much weaker in the rapidly dried than in the slowly dried embryos. We interpreted the molecular packing to be “less tight” in the rapidly dried embryos. Whereas sucrose (Suc) is the major soluble carbohydrate after fast drying, upon slow drying the trisaccharide umbelliferose accumulates at the expense of Suc. The possibly protective role of umbelliferose was tested on protein and phospholipid model systems, using Suc as a reference. Both umbelliferose and Suc form a stable glass with drying: They depress the transition temperature of dry liposomal membranes equally well, they both prevent leakage from dry liposomes after rehydration, and they protect a polypeptide that is desiccation sensitive. The similar protection properties in model systems and the apparent interchangeability of both sugars in viable, dry somatic embryos suggest no special role of umbelliferose in the improved physical stability of the slowly dried embryos. Also, during slow drying LEA (late-embryogenesis abundant) transcripts are expressed. We suggest that LEA proteins embedded in the glassy matrix confer stability to these slowly dried embryos

On the tertiary structure of poly-carbenes; Self-assembly of sp\u3csup\u3e3\u3c/sup\u3e-carbon-based polymers into liquid-crystalline aggregates

\u3cp\u3eThe self-assembly of poly(ethylidene acetate) (st-PEA) into van der Waals-stabilized liquid-crystalline (LC) aggregates is reported. The LC behavior of these materials is unexpected, and unusual for flexible sp \u3csup\u3e3\u3c/sup\u3e-carbon backbone polymers. Although the dense packing of polar ester functionalities along the carbon backbone of st-PEA could perhaps be expected to lead directly to rigid-rod behavior, molecular modeling reveals that individual st-PEA chains are actually highly flexible and should not reveal rigid-rod induced LC behavior. Nonetheless, st-PEA clearly reveals LC behavior, both in solution and in the melt over a broad elevated temperature range. A combined set of experimental measurements, supported by MM/MD studies, suggests that the observed LC behavior is due to self-aggregation of st-PEA into higher-order aggregates. According to MM/MD modeling st-PEA single helices adopt a flexible helical structure with a preferred trans-gauche syn-syn-anti-anti orientation. Unexpectedly, similar modeling experiments suggest that three of these helices can self-assemble into triple-helical aggregates. Higher-order assemblies were not observed in the MM/MD simulations, suggesting that the triple helix is the most stable aggregate configuration. DLS data confirmed the aggregation of st-PEA into higher-order structures, and suggest the formation of rod-like particles. The dimensions derived from these light-scattering experiments correspond with st-PEA triple-helix formation. Langmuir-Blodgett surface pressure-area isotherms also point to the formation of rod-like st-PEA aggregates with similar dimensions as st-PEA triple helixes. Upon increasing the st-PEA concentration, the viscosity of the polymer solution increases strongly, and at concentrations above 20 wt % st-PEA forms an organogel. STM on this gel reveals the formation of helical aggregates on the graphite surface-solution interface with shapes and dimensions matching st-PEA triple helices, in good agreement with the structures proposed by molecular modeling. X-ray diffraction, WAXS, SAXS and solid state NMR spectroscopy studies suggest that st-PEA triple helices are also present in the solid state, up to temperatures well above the melting point of st-PEA. Formation of higher-order aggregates explains the observed LC behavior of st-PEA, emphasizing the importance of the tertiary structure of synthetic polymers on their material properties. Coming around again: The self-assembly of polycarbenes into van der Waals stabilized liquid-crystalline (LC) aggregates is described. The LC behavior of these materials is unexpected for flexible sp\u3csup\u3e3\u3c/sup\u3e-carbon backbone polymers. The experimental measurements, supported by molecular mechanics-based molecular dynamic studies, suggest that the LC behavior is due to self-aggregation of st-PEA into triple-helix aggregates (st-PEA=syndiotactic poly(ethylidene acetate).\u3c/p\u3