INTEGRATIVE PHYSIOLOGY AS A TOOL FOR MEDICAL EDUCATION TRANSFORMATION

Given the rapid progress of modern science, integrative physiology holds a key place in medical education, as it studies patterns of human body functioning in terms of individual characteristics, epigenetic factors and endogenous effects on cellular mechanisms. Drawing on five years of experience in teaching physiology at Danylo Halytsky Lviv National Medical University, we highlight the importance of implementing applied integrative physiology in the training of future doctors. We present interpretation of physiological phenomena, adaptive mechanisms and compensation resources in the human body. The introduction of methods for assessing human functions in real time based on high-precision registration of individual functional characteristics and adaptive physiological mechanisms with high diagnostic value, allows future doctors to develop clinical competencies in modern principles of medical science, personalized medicine, and preventive healthcare strategies

Cell scientist to watch – Prachee Avasthi

ABSTRACT Prachee Avasthi studied Molecular and Integrative Physiology at the University of Illinois at Urbana-Champaign. She received her PhD in neuroscience in 2009 from the lab of Wolfgang Baehr at the University of Utah for her work on the control of membrane protein trafficking in photoreceptors. Prachee then moved to Wallace Marshall's group at the University of California, San Francisco, for her postdoc, where she studied ciliary assembly and the regulation of ciliary length. She set up her lab at the University of Kansas Medical Center in 2015, and relocated to the Geisel School of Medicine at Dartmouth in 2020, where she is an Associate Professor of Biochemistry and Cell Biology. Her group investigates the biogenesis of cilia and the coordination of actin- and microtubule-based trafficking.

Arcuate nucleus-dependent regulation of metabolism - pathways to obesity and diabetes mellitus

The central nervous system (CNS) receives information from afferent neurons, circulating hormones and absorbed nutrients and integrates this information to orchestrate the actions of the neuroendocrine and autonomic nervous systems in maintaining systemic metabolic homeostasis. Particularly the arcuate nucleus of the hypothalamus (ARC) is of pivotal importance for primary sensing of adiposity signals, such as leptin and insulin, and circulating nutrients, such as glucose. Importantly, energy state-sensing neurons in the ARC not only regulate feeding but at the same time control multiple physiological functions, such as glucose homeostasis, blood pressure and innate immune responses. These findings have defined them as master regulators, which adapt integrative physiology to the energy state of the organism. The disruption of this fine-tuned control leads to an imbalance between energy intake and expenditure as well as deregulation of peripheral metabolism. Improving our understanding of the cellular, molecular and functional basis of this regulatory principle in the CNS could set the stage for developing novel therapeutic strategies for the treatment of obesity and metabolic syndrome. In this review, we summarize novel insights with a particular emphasis on ARC neurocircuitries regulating food intake and glucose homeostasis and sensing factors that inform the brain of the organismal energy status.

Breath-Hold Diving – The Physiology of Diving Deep and Returning

Breath-hold diving involves highly integrative physiology and extreme responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. With astonishing depth records exceeding 100 m, and up to 214 m on a single breath, the human capacity for deep breath-hold diving continues to refute expectations. The physiological challenges and responses occurring during a deep dive highlight the coordinated interplay of oxygen conservation, exercise economy, and hyperbaric management. In this review, the physiology of deep diving is portrayed as it occurs across the phases of a dive: the first 20 m; passive descent; maximal depth; ascent; last 10 m, and surfacing. The acute risks of diving (i.e., pulmonary barotrauma, nitrogen narcosis, and decompression sickness) and the potential long-term medical consequences to breath-hold diving are summarized, and an emphasis on future areas of research of this unique field of physiological adaptation are provided.

The Pitfalls of in vivo Cardiac Physiology in Genetically Modified Mice – Lessons Learnt the Hard Way in the Creatine Kinase System

In order to fully understand gene function, at some point, it is necessary to study the effects in an intact organism. The creation of the first knockout mouse in the late 1980’s gave rise to a revolution in the field of integrative physiology that continues to this day. There are many complex choices when selecting a strategy for genetic modification, some of which will be touched on in this review, but the principal focus is to highlight the potential problems and pitfalls arising from the interpretation of in vivo cardiac phenotypes. As an exemplar, we will scrutinize the field of cardiac energetics and the attempts to understand the role of the creatine kinase (CK) energy buffering and transport system in the intact organism. This story highlights the confounding effects of genetic background, sex, and age, as well as the difficulties in interpreting knockout models in light of promiscuous proteins and metabolic redundancy. It will consider the dose-dependent effects and unintended consequences of transgene overexpression, and the need for experimental rigour in the context of in vivo phenotyping techniques. It is intended that this review will not only bring clarity to the field of cardiac energetics, but also aid the non-expert in evaluating and critically assessing data arising from in vivo genetic modification.

112 Chronic sleep restriction disrupts slow-wave sleep homeostatic regulation and damages monoaminergic structures in the rat brain

Introduction The neurophysiological mechanisms underlying long-term neurological and cognitive disorders associated with chronic sleep restriction (CSR) are not fully understood. Here we evaluated how the sleep-wake cycle changes during and after a period of sleep restriction in rats, and whether CSR results in neurodegeneration in monoaminergic brain structures. Methods For CSR, 7-8-month-old Wistar rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 5 days on the orbital shaker. Telemetric sleep recordings were made before, during, and after CSR. Neurodegeneration in brain monoaminergic structures was assessed immunohistochemically. Results During SD, wakefulness comprised 85% of the total registration time; the remaining time was represented by drowsiness with low EEG delta power. Rapid eye movement sleep (REMS) was absent. During CSR, slow-wave sleep (SWS) and REMS were reduced by 62% and 57%. Total SWS time during SO periods increased on the first CSR day, but decreased to the baseline by the fifth CSR day. SWS EEG delta power (a measure of sleep intensity) decreased gradually from the first to the fifth CSR day. REMS total time remained elevated during all SO periods. During the first recovery day after CSR, SWS did not change, but REMS increased by 30%. No changes in total sleep time were found on the second recovery day but sleep intensity was decreased. In 14 days after CSR, all sleep parameters returned to the baseline. We revealed a loss of 24% of noradrenergic locus coeruleus neurons, 29% and 17% of dopaminergic neurons in the substantia nigra, the ventral tegmental area as well as in their striatal terminals. Conclusion We consider CSR as a damaging factor leading to a gradual suppression of homeostatic mechanisms governing sleep recovery. CSR can provoke neurodegeneration in monoaminergic structures involved in the regulation of emotional behavior, sleep, and autonomic functions. Support (if any) Ministry of Science and Higher Education of the Russian Federation grant (No. 075-15-2020-916 dated November 13, 2020) for the establishment and development of the Pavlovsky Center “Integrative Physiology for Medicine, High-Tech Healthcare and Stress Resilience Technologies”.