Neuromuscular Electrical Stimulation of the Quadriceps in Patients with Non-Small Cell Lung Cancer Receiving Palliative Chemotherapy: A Randomized Phase II Study

Background

A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC). Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES) of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.

Methods

Patients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.

Results

49 patients (28 male, median (IQR) age 69 (64−75) years) participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71]) met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.

Conclusions

NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.

Trial Registration

Current Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026     

Comparative palynology and wood anatomy of <Emphasis Type="Italic">Taxodium distichum</Emphasis> (L.) Rich. and <Emphasis Type="Italic">Taxodium mucronatum</Emphasis> Ten.

A comparative study of Taxodium distichum (L.) Rich. and Taxodium mucronatum Ten. was carried out on the basis of pollen morphology and wood anatomy by light and scanning electron microscopy. We describe a detailed analysis of the anatomical characteristics of the wood, including the tracheids, ray parenchyma, axial parenchyma and number of cross-field pits. Palynological characters were also studied to reveal the shape, size and ultrastructure of the pollen grains. These studies give taxonomic support for the recognition of T. distichum and T. mucronatum as two different species.     

In silico Platform for Prediction of N-, O- and C-Glycosites in Eukaryotic Protein Sequences

Glycosylation is one of the most abundant and an important post-translational modification of proteins. Glycosylated proteins (glycoproteins) are involved in various cellular biological functions like protein folding, cell-cell interactions, cell recognition and host-pathogen interactions. A large number of eukaryotic glycoproteins also have therapeutic and potential technology applications. Therefore, characterization and analysis of glycosites (glycosylated residues) in these proteins is of great interest to biologists. In order to cater these needs a number of in silico tools have been developed over the years, however, a need to get even better prediction tools remains. Therefore, in this study we have developed a new webserver GlycoEP for more accurate prediction of N-linked, O-linked and C-linked glycosites in eukaryotic glycoproteins using two larger datasets, namely, standard and advanced datasets. In case of standard datasets no two glycosylated proteins are more similar than 40%; advanced datasets are highly non-redundant where no two glycosites’ patterns (as defined in methods) have more than 60% similarity. Further, based on our results with several algorihtms developed using different machine-learning techniques, we found Support Vector Machine (SVM) as optimum tool to develop glycosite prediction models. Accordingly, using our more stringent and non-redundant advanced datasets, the SVM based models developed in this study achieved a prediction accuracy of 84.26%, 86.87% and 91.43% with corresponding MCC of 0.54, 0.20 and 0.78, for N-, O- and C-linked glycosites, respectively. The best performing models trained on advanced datasets were then implemented as a user-friendly web server GlycoEP (http://www.imtech.res.in/raghava/glycoep/). Additionally, this server provides prediction models developed on standard datasets and allows users to scan sequons in input protein sequences.     

α-Tocopherol Application Modulates the Response of Wheat (Triticum aestivum L.) Seedlings to Elevated Temperatures by Mitigation of Stress Injury and Enhancement of Antioxidants

Wheat seedlings (4 days old) were subjected to varying temperatures of 25, 30, and 35 °C for 7 days in a growth chamber under hydroponic conditions in the absence or presence of α-tocopherol (5 μM). The growth of shoots and roots was inhibited severely at 35 °C. The endogenous α-tocopherol increased in the shoots at 30 °C over the controls but decreased significantly at 35 °C over the previous temperature. The exogenous application of α-tocopherol elevated the endogenous levels in the heat-stressed plants, which were consequently able to maintain significantly greater growth associated with reduction in damage to membranes, cellular oxidizing ability, chlorophyll content, and photochemical efficiency in shoots. The relative leaf water content and stomatal conductance were not affected significantly with the application of tocopherol. The oxidative stress induced by high temperature (35 °C) in terms of malondialdehyde and hydrogen peroxide contents was significantly lower in the presence of α-tocopherol. The enzymatic antioxidants such as superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase showed considerable reduction in their activities at 35 °C compared to those at 30 °C, with greater effects on APX and GR. The nonenzymatic antioxidants like ascorbate, glutathione, and proline increased at 30 °C but decreased appreciably at 35 °C, suggesting impairment in their synthesis at stressful temperatures. α-Tocopherol-treated plants, especially those growing at 35 °C, had improved levels of enzymatic and nonenzymatic antioxidants. These observations provided evidence about the involvement of α-tocopherol in governing heat sensitivity in wheat and suggested manipulation of its endogenous levels to induce heat tolerance in this crop.