From heart to muscle: Pathophysiological mechanisms underlying long-term physical sequelae from SARS-CoV-2 infection

The long-term sequelae of the coronavirus disease 2019 (COVID-19) are multifaceted and, besides the lungs, impact other organs and tissues, even in cases of mild infection. Along with commonly reported symptoms such as fatigue and dyspnea, a significant proportion of those with prior COVID-19 infection also exhibit signs of cardiac damage, muscle weakness, and ultimately, poor exercise tolerance. This review provides an overview of evidence indicating cardiac impairments and persistent endothelial dysfunction in the peripheral vasculature of those previously infected with COVID-19, irrespective of the severity of the acute phase of illness. Additionally, VO2peak appears to be lower in convalescent patients, which may stem, in part, from alterations in O2 transport such as impaired diffusional O2conductance. Together, the persistent multi-organ dysfunction induced by COVID-19 may set previously healthy individuals on a trajectory towards frailty and disease. Given the large proportion of individuals recovering from COVID-19, it is critically important to better understand the physical sequelae of COVID-19, the underlying biological mechanisms contributing to these outcomes, and the long-term effects on future disease risk. This review highlights relevant literature on the pathophysiology post-COVID-19 infection, gaps in the literature, and emphasizes the need for the development of evidence-based rehabilitation guidelines.

From What to Why, the Growing Need for a Focus Shift Toward Explainability of AI in Digital Pathology

While it is impossible to deny the performance gains achieved through the incorporation of deep learning (DL) and other artificial intelligence (AI)-based techniques in pathology, minimal work has been done to answer the crucial question of why these algorithms predict what they predict. Tracing back classification decisions to specific input features allows for the quick identification of model bias as well as providing additional information toward understanding underlying biological mechanisms. In digital pathology, increasing the explainability of AI models would have the largest and most immediate impact for the image classification task. In this review, we detail some considerations that should be made in order to develop models with a focus on explainability.

Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here, we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between the different host species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. These data will aid the selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

Biology of increased tolerance and validation of the psychoactive substance dependence

The article shows that the current level of physiology does not disclose the biological mechanisms of the organism transition from one range to adapt to a higher with an increase in the regular forces of the stimulus above sub-extreme. A new trend in the physiology of adaptation - proqredient adaptation, explains the mechanism of increasing the tolerance of the organism, with dependence on psychoactive substances (PAS ). It is scientifically proved, that dependences of the organism on PAS are the states of progredient adaptation.

Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities

The Wnt/β-catenin pathway comprises a family of proteins that play critical roles in embryonic development and adult tissue homeostasis. The deregulation of Wnt/β-catenin signalling often leads to various serious diseases, including cancer and non-cancer diseases. Although many articles have reviewed Wnt/β-catenin from various aspects, a systematic review encompassing the origin, composition, function, and clinical trials of the Wnt/β-catenin signalling pathway in tumour and diseases is lacking. In this article, we comprehensively review the Wnt/β-catenin pathway from the above five aspects in combination with the latest research. Finally, we propose challenges and opportunities for the development of small-molecular compounds targeting the Wnt signalling pathway in disease treatment.

Effects of Microenvironmental Factors on Assessing Nanoparticle Toxicity

Nanoparticles, such as dust or fine particles produced from diverse sources, are regarded as hazardous materials to human organs, and the interest in understanding their biological mechanisms and evaluating the...

Tolerance to extreme doses of psychoactive substances

The article shows that the current level of physiology does not disclose the biological mechanisms of the organism’s transition from one range to adapt to a higher one with an increase in the regular forces of the stimulus above sub-extreme. A new trend in the physiology of adaptation - proqredient adaptation, explains the mechanism of increasing the tolerance of the organism, with dependence on psychoactive substances (PAS). Scientific has reasonably shown that depending on the organism from PAS - not the disease, and the states like proqredient adaptation.

Smoking as an environmental hazard to the periodontal and peri-implant tissues: A brief review

While dental plaque is considered the etiological factor for the development of periodontal and peri-implant diseases, many studies from recent years point to smoking as the most significant environmental factor contributing to disease severity. This effect is evident at the epidemiological level as well as on our understanding of the biological mechanisms involved. The present review presents abundant scientific evidence showing that smoking negatively affects the local blood supply, interferes with the reaction of the immune system to bacterial insult, is toxic to gingival and periodontal ligament cells, impedes the response of the periodontal attachment apparatus to treatment, and is linked to dental implant failure. Over the past 30 years, more than 200 million people have died as a result of smoking tobacco use. There are more than 1 billion current smokers worldwide and these numbers are likely to increase over the coming years. And yet, the effect of smoking on periodontal and peri-implant health has been a controversial issue. It was argued, that it is difficult to prove such an effect due to poor adherence of smokers to oral hygiene, which creates a confounding factor inseparable from the effect of the smoking itself. Unfortunately, even some of the more recent publications cast doubt as for the importance of smoking cessation on peri-implant health, as a prerequisite for a successful treatment. The aim of the present review was to question the validity of these reports by presenting multiple evidence to support the quiet widely accepted common knowledge that is the numerous hazards to the oral biology which are the result of a heavy and prolonged smoking habit.