Evolutionary Changes in Pathology and Our Understanding of Disease.

The history of pathology involves human dissections, autopsies, microscopy, as well as the development of histopathological, immunohistochemical, and molecular techniques. Through these methods, our understanding of anatomy and disease improved, and models of pathogenesis were gradually refined over time. This review discusses key milestones in the development of pathology as a branch of medical science, from ancient civilizations to the modern day.

Eosinophilic angiocentric fibrosis and immunoglobulin 4-related disease revisited.

Eosinophilic angiocentric fibrosis (EAF) has been postulated to lie on the spectrum of IgG4-related disease (IgG4-RD) in a study reported in 2011. However, the aetiology of EAF remains controversial, despite increasing literature reporting IgG4-RD targeted investigations in those studies. This review aims to formally evaluate the relationship between EAF and IgG4-RD using the latest 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification scheme for IgG4-RD. A literature search was performed on the PubMed database for all studies describing patients diagnosed with EAF. Additionally, two EAF cases were retrospectively identified from our institution and presented. The demographics, clinical presentation, histological and serological data of each patient were analysed. A total of 20 cases were evaluated, including 18 patients from 14 articles in the English literature and two cases from our institution. Six of 20 (30%) patients with EAF met the criteria for IgG4-RD with the 2019 ACR/EULAR classification scheme. This represents the first attempt at formally evaluating the relationship between EAF and IgG4-RD using a validated set of classification criteria. Using the currently available data, a small proportion of patients with EAF met the criteria for IgG4-RD. However, various limitations of this study suggest that further efforts at disease characterization of EAF may be required.

The Challenge of "Monomorphic" Mucoepidermoid Carcinoma-Report of a Rare Case with Pure Spindle-Clear Cell Morphology.

BACKGROUND: Mucoepidermoid carcinoma is a malignant salivary gland tumor which, in most cases, is composed of variable proportions of mucous, epidermoid, and intermediate cells. METHODS: We report a case of parapharyngeal mucoepidermoid carcinoma with highly unusual ("monomorphic") light microscopic features as well as atypical immunohistochemical properties. Molecular analysis was performed using the TruSight RNA fusion panel. RESULTS: The tumor featured heretofore undescribed histopathological features: sheets and nests composed of monomorphic neoplastic (plump spindle to epithelioid) cells with no mucous, intermediate, glandular/columnar, or any other cell type identified. The neoplastic cells displayed variable clear cell change and only expressed cytokeratin 7. Despite this non-classical morphology, the presence of the classical CRTC1::MAML2 fusion was demonstrated. CONCLUSIONS: Mucoepidermoid carcinoma featuring a uniform ("monomorphic") population of neoplastic cells is a novel observation. A confident diagnosis of mucoepidermoid carcinoma can be made upon detection of the CRTC1/3::MAML2 fusion. Our case increases the spectrum of histopathological appearances that mucoepidermoid carcinoma may display.

Scoping review and international multi-centre cohort study investigating teaching, knowledge and beliefs regarding physical activity as a health intervention among medical students: a comparison between Singapore and the UK.

INTRODUCTION: Physical inactivity is a global challenge and physicians must promote physical activity (PA) among their patients. Nevertheless, PA counselling remains inadequate due to limitations in knowledge, education and information availability. This study evaluates the understanding of PA as a health intervention and knowledge of World Health Organization (WHO) guidelines among Singapore and United Kingdom (UK) medical students, the next generation of physicians. METHODS: Students from Singapore (Yong Loo Lin School of Medicine and Lee Kong Chian School of Medicine) and the UK (Universities of Cardiff, Leicester, Oxford and Birmingham) were invited to complete a 12-item online survey. Questions assessed knowledge of WHO guidelines, understanding of PA in health and illness, personal PA levels and exposure to PA counselling in clinical practice. RESULTS: Among 633 Singapore and UK students who completed the questionnaire, 94.8% believed that PA was important in preventing disease, but only 70.9% recognised its importance in treating disease. The majority (85.3%) indicated participation in PA and exercise. General understanding of WHO guidelines for adults was poor, with less than half (46.8%) correctly answering this section. 3 (0.5%) students identified that PA in adults could be accumulated in multiple ways. Understanding of PA in health and familiarity with guidelines did not differ significantly between Singapore and UK students. CONCLUSION: There is considerable room for improvement in the knowledge of WHO guidelines and the role of PA in health. Education should begin during the undergraduate phase so that future doctors are better equipped to counsel their patients.

Structures of Zika virus NS2B-NS3 protease in complex with peptidomimetic inhibitors.

Zika virus NS2B-NS3 protease plays an essential role in viral replication by processing the viral polyprotein into individual proteins. The viral protease is therefore considered as an ideal antiviral drug target. To facilitate the development of protease inhibitors, we report three high-resolution co-crystal structures of bZiPro with peptidomimetic inhibitors composed of a P1-P4 segment and different P1' residues. Compounds 1 and 2 possess small P1' groups that are split off by bZiPro, which could be detected by mass spectrometry. On the other hand, the more potent compound 3 contains a bulky P1' benzylamide structure that is resistant to cleavage by bZiPro, demonstrating that presence of an uncleavable C-terminal cap contributes to a slightly improved inhibitory potency. The N-terminal phenylacetyl residue occupies a position above the P1 side chain and therefore stabilizes a horseshoe-like backbone conformation of the bound inhibitors. The P4 moieties show unique intra- and intermolecular interactions. Our work reports the detailed binding mode interactions of substrate-analogue inhibitors within the S4-S1' pockets and explains the preference of bZiPro for basic P1-P3 residues. These new structures of protease-inhibitor complexes will guide the design of more effective NS2B-NS3 protease inhibitors with improved potency and bioavailability.