Highlights► Previous single mutants of transketolase improved activity on new substrates. ► Recombination to form double mutants led to critical loss of functional expression. ► Mutated sites were found to be in a structural network of co-evolved residues. ► The network was re-adapted around previous mutants for kinetic synergy and functional expression.

Data have emerged that the addition of concurrent chemotherapy to radiation can lead to swallowing dysfunction that may have an impact on patient quality of life and lead to significant morbidities such as poor nutritional status, enteral feeding tube dependence, and aspiration pneumonia. Although intensity-modulated radiation therapy (IMRT) for head and neck cancer was initially developed to spare the parotid gland to reduce xerostomia, attention has recently focused on its utility to selectively decrease radiation dose to specified anatomic structures responsible for a functional swallow. Recent reports have proposed a variety of dose thresholds or constraints to these swallowing-related structures, which may guide IMRT planning with the aim of reducing dysphagia. This critical review of the current literature assesses the feasibility of IMRT to maintain swallowing function and appraises the various dosimetric parameters that have been proposed to help minimize long-term dysphagia.

ME, Cui J, et al. Clinical-dosimetric Objective: To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours. Methods: 40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V 10 , V 20 and V 30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC). Results:The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V 10 , V 20 and V 30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 31 toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V 20 was identified as the most significant predictor of late toxicity (AIC, 26.81). Conclusion: A dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future. Advances in knowledge: A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.

Pathological examination and laboratory results demonstrated EATL, type 2, which is not associated with celiac disease. A review of the literature on EATL is also presented.

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