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Background and purposeIn developing countries like Pakistan the cost effectiveness and patient convenience in any treatment modality is a question of major concern. The purpose of this study was two-fold; first to report our experience with a high-dose rate Iridium-192 surface mould brachytherapy of keloid scars after surgical excision, using different radiation treatment regimen and second to establish the most convenient and cost effective treatment protocol having no compromise on the treatment outcomes.Materials and methodsFrom January 2012 to April 2015 a total 51 patients with 65 keloid lesions underwent postoperative Iridium-192 high-dose rate surface mould brachytherapy. The dose regimen used was: 8 Gy in a single fraction, 10 Gy in a single fraction, 15 Gy in three fractions and 18 Gy in three fractions. The median follow-up period was 33 months (range 15–53 months).ResultsThe success rates were 57·2, 89·5, 85 and 89·5% for the treatment regimen of 8 Gy/F×1, 10 Gy/F×1, 5 Gy/F×3 and 6 Gy/F×3, respectively. Grade 2 or above radiation induced toxicity was not observed.FindingsThe results of this study show that a dose regimen of 10 Gy (biological effective dose=20 Gy) in a single fraction have comparable results with a dose regimen of 15 Gy in three fractions or 18 Gy in three fractions. 10 Gy in a single fraction is therefore the most convenient and cost effective dose regimen for the management of keloid scars in developing countries like Pakistan, while 8 Gy in a single fraction is considered suboptimal and discouraged in practice. [ABSTRACT FROM PUBLISHER]

IntroductionIn non-melanoma skin cancer—that is, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)—brachytherapy treatment is preferred over surgical excision because of cosmetic reasons, acceptability and preference of patients.Material and methodsMoulds are prepared of wax to match the size of the lesion. This represents the area to be considered in treatment planning. A total of 85 patients who had either SCC or BCC were treated, and all these patients were classified on the basis of age, gender and origin.ResultsPatients were treated with 39 Gy in 13 fractions (biological effective dose=50·7 Gy). In 52 BCC patients, treatment achieved excellent cosmetic results in 49 cases, with 17 of these patients experiencing Grade-1 skin reactions related to treatment in the first 24 weeks of follow-up. A single patient experienced Grade-II hyper-pigmentation reaction in the third week. In 33 SCC patients, treatment achieved excellent cosmetic results in 28 cases, with 17 of these patients experiencing Grade-I reaction in the first 36 weeks after treatment. Among the remaining four patients, only one developed Grade-II hypo-pigmentation and one patient experienced tumour recurrence near the primary site. The overall outcome efficacy of the treatment was 98·8%.FindingsThe treatment outcome not only enhances our confidence in brachytherapy but also improves the patient’s satisfaction regarding cosmetic results and curative output achieved by avoiding a surgical procedure for non-melanoma skin cancers. [ABSTRACT FROM PUBLISHER]

The formation of neurofibrillary tangles (NFT) with β-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer's Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel β-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies. [ABSTRACT FROM AUTHOR]