METHODOLOGY: The study was conducted at a major foot and ankle referral center in Wythenshawe, Manchester, UK. Thirty-eight Computed Tomography (CT) scans were evaluated by 20 independent raters: 15 general orthopedic and trauma surgeons plus five foot and ankle surgeons. Each rater classified the posterior malleolus fracture according to M&M classification into type 1, 2A, 2B, 3, or not classifiable. Statistical analysis was done with the R software package and SPSS (v26; IBM Corp., Armonk, NY). Fleiss kappa (κ) coefficient with a 95% confidence interval (CI) was applied.
RESULTS: The interobserver agreement was moderate with a global κ value of 0.531 (95% CI: 0.518, 0.544). There were good agreements for identifying type 3 M&M (κ=0.785) and those that are not applicable for M&M classification (κ=0.785). There was a strong correlation between all raters in using M&M classification (Tb=0.53-0.59) except for Rater 12.
CONCLUSION: M&M classification remains a valuable tool to guide the management of patients with these subsets of ankle fractures.
INTRODUCTION: Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived thiazoline-based polypeptides (CTBCs), exhibit a wide array of pharmacological activities due to their unique structural features and interesting bioactions, which furnish them as promising leads for drug discovery.
METHODS: In the present study, we comprehensively review the natural sources, distinguishing chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities counting the mode of actions for biological portrayals which render CTBCs as indispensable sources for emergence of prospective peptide-based therapeutics. In this milieu, metal organic frameworks and their biomedical applications are also briefly discussed. To boot, the challenges, approaches, and clinical status of peptide-based therapeutics are conferred.
RESULTS: Based on these analyses, CTBCs can be appraised as ideal drug targets that have always remained a challenge for traditional small molecules, like those involved in protein- protein interactions or to be developed as potential cancer-targeting nanomaterials. Cyclization-induced reduced conformational freedom of these cyclooligopeptides contribute to improved metabolic stability and binding affinity to their molecular targets. Clinical success of several cyclic peptides provokes the large library-screening and synthesis of natural product-like cyclic peptides to address the unmet medical needs.
CONCLUSION: CTBCs can be considered as the most promising lead compounds for drug discovery. Adopting the amalgamation of advanced biological and biopharmaceutical strategies might endure these cyclopeptides to be prospective biomolecules for futuristic therapeutic applications in the coming times.
METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review.
FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.