Pathology Education Powered by Virtual and Digital Transformation: Now and the Future

[...]standing on the crest of yet another wave of change, driven by artificial intelligence (AI) and machine learning,2 pathology educators may soon be challenged to convey the best ways to apply these tools to the problems of diagnostic pathology for the coming generation of learners and the present corps of practitioners.3 Hence, this collaborative effort aims to describe the genetic code governing the transmission of pathology knowledge to subsequent generations of medical professionals.4 We aim to expose not just the code but also the supporting array of catalysts, enhancers, and other cofactors now in place to ensure we have a robust and potent supply of pathologists. APPLYING DP IN UNDERGRADUATE MEDICAL, DENTAL, VETERINARY, AND ALLIED HEALTH EDUCATION Beginning in 1985, this technology has been progressively more widely implemented in undergraduate medical, dental, veterinary, and allied health (nursing, pharmacy, medical technology, etc) education platforms in the United States and internationally.5,11-26 As noted above, virtual microscopy laboratories, available on personal devices or in school-based computer labs, have replaced fixed laboratories housing gross specimens, boxes of glass slides, and student microscopes. WSI with links to supplementary resources, such as gross and radiologic images and additional study material, provide enrichment for the teaching and learning experience in the new virtual environment. [...]significant exposure to microanatomy and the laboratory methods of pathology underpinning so much of diagnosis, therapy, and management is foundational.

Disparities in COVID-19 incidence and fatality rates at high-altitude.

Background: SARS-CoV-2 has affected every demography disproportionately, including even the native highland populations. Hypobaric-hypoxic settings at high-altitude (HA, >2,500 masl) present an extreme environment that impacts the survival of permanent residents, possibly including SARS-CoV-2. Conflicting hypotheses have been presented for COVID-19 incidence and fatality at HA. Objectives: To evaluate protection or risk against COVID-19 incidence and fatality in humans under hypobaric-hypoxic environment of high-altitude (>2,501 masl). Methods: Global COVID-19 data of March 2020-21, employed from official websites of the Indian Government, John Hopkins University, and Worldometer were clustered into 6 altitude categories. Clinical cofactors and comorbidities data were evaluated with COVID-19 incidence and fatality. Extensive comparisons and correlations using several statistical tools estimated the risk and protection. Results: Of relevance, data analyses revealed four distinct responses, namely, partial risk, total risk, partial protection, and total protection from COVID-19 at high-altitude indicating a mixed baggage and complexity of the infection. Surprisingly, it included the countries within the same geographic region. Moreover, body mass index, hypertension, and diabetes correlated significantly with COVID-19 incidence and fatality rate (P ≤ 0.05). Conclusions: Varied patterns of protection and risk against COVID-19 incidence and fatality were observed among the high-altitude populations. It is though premature to generalize COVID-19 effects on any particular demography without further extensive studies.

Mapping of functional SARS-CoV-2 receptors in human lungs establishes differences in variant binding and SLC1A5 as a viral entry modulator of hACE2.

BACKGROUND: The COVID-19 pandemic is an infectious disease caused by SARS-CoV-2. The first step of SARS-CoV-2 infection is the recognition of angiotensin-converting enzyme 2 (ACE2) receptors by the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein. Although the molecular and structural bases of the SARS-CoV-2-RBD/hACE2 interaction have been thoroughly investigated in vitro, the relationship between hACE2 expression and in vivo infection is less understood. METHODS: Here, we developed an efficient SARS-CoV-2-RBD binding assay suitable for super resolution microscopy and simultaneous hACE2 immunodetection and mapped the correlation between hACE2 receptor abundance and SARS-CoV-2-RBD binding, both in vitro and in human lung biopsies. Next, we explored the specific proteome of SARS-CoV-2-RBD/hACE2 through a comparative mass spectrometry approach. FINDINGS: We found that only a minority of hACE2 positive spots are actually SARS-CoV-2-RBD binding sites, and that the relationship between SARS-CoV-2-RBD binding and hACE2 presence is variable, suggesting the existence of additional factors. Indeed, we found several interactors that are involved in receptor localization and viral entry and characterized one of them: SLC1A5, an amino acid transporter. High-resolution receptor-binding studies showed that co-expression of membrane-bound SLC1A5 with hACE2 predicted SARS-CoV-2 binding and entry better than hACE2 expression alone. SLC1A5 depletion reduces SARS-CoV-2 binding and entry. Notably, the Omicron variant is more efficient in binding hACE2 sites, but equally sensitive to SLC1A5 downregulation. INTERPRETATION: We propose a method for mapping functional SARS-CoV-2 receptors in vivo. We confirm the existence of hACE2 co-factors that may contribute to differential sensitivity of cells to infection. FUNDING: This work was supported by an unrestricted grant from "Fondazione Romeo ed Enrica Invernizzi" to Stefano Biffo and by AIRC under MFAG 2021 - ID. 26178 project - P.I. Manfrini Nicola.

Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies.

RNA-dependent RNA polymerases (RdRPs) represent a distinctive yet versatile class of nucleic acid polymerases encoded by RNA viruses for the replication and transcription of their genome. The structure of the RdRP is comparable to that of a cupped right hand consisting of fingers, palm, and thumb subdomains. Despite the presence of a common structural core, the RdRPs differ significantly in the mechanistic details of RNA binding and polymerization. The present review aims at exploring these incongruities in light of recent structural studies of RdRP complexes with diverse cofactors, RNA moieties, analogs, and inhibitors.

Choroba koronawirusowa 2019 (COVID-19) a stan odżywienia i sposób żywienia – przegląd literatury

Introduction and objective: Currently, the world is affected by the pandemic caused by coronavirus disease (COVID-19), which strongly affects the health care system. Dietary habits and nutritional status of the body significantly influence the course and outcome of COVID-19 treatment. The aim of this study is the summary of the current knowledge about the impact of dietary habits and nutritional status on the development and course of coronavirus disease and the presentation of nutritional recommendations for the dietary management in COVID-19 treatment. Review methods: The PubMed database and the official websites of medical organizations and associations were searched for the English phrases ‘COVID-19’, ‘SARS-CoV-2’, ‘nutrition’, ‘diet’. Abbreviated description of the state of knowledge: Chronic inflammation, immune system disorders, chronic diseases, nutritional status disorders and deficiency of nutrients might present possible factors associated with the severity and course of COVID-19. The nutrients play a direct role as cofactors and regulators of the immune system and reveal antiinflammatory effects. The supply of zinc, selenium, copper, iron, vitamin D, A, C, and B-group, as well as probiotics is important for the optimal function of the immune system. Deficiency of this micronutrients plays a remarkable role in an adverse course of COVID-19. Summary: The nutritional status of the body, dietary habits including the supply of necessary nutrients can have an impact of the reduction of susceptibility and alleviate the adverse consequences of coronavirus disease. The role of diet and nutritional interventions in COVID-19 is highly promising. This area of study is innovative;therefore, further investigations are needed to justify specific benefits from these actions for combating coronavirus disease.

Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts.