Physiological Role Research Articles

Characterizing patterns of diffusion tensor imaging variance in aging brains.

As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Here we characterize the role of physiology, subject compliance, and the interaction of subject with the scanner in the understanding of DTI variability, as modeled in spatial variance of derived metrics in homogeneous regions. We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging (BLSA), with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related ( p ≪ 0.001) to FA variance in the cuneus and occipital gyrus, but negatively ( p ≪ 0.001) in the caudate nucleus. Males show significantly ( p ≪ 0.001) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated ( p < 0.05) with a decrease in FA variance. Head motion increases during the rescan of DTI (Δ μ = 0.045 millimeters per volume). The effects of each covariate on DTI variance, and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.

Role of physiology in the management of multivessel disease among patients with acute coronary syndrome.

Multivessel coronary artery disease (CAD), defined as ≥50% stenosis in 2 or more epicardial arteries, is associated with a high burden of morbidity and mortality in acute coronary syndrome (ACS) patients. A salient challenge for managing this cohort is selecting the optimal revascularisation strategy, for which the use of coronary physiology has been increasingly recognised. Fractional flow reserve (FFR) is an invasive, pressure wire-based, physiological index measuring the functional significance of coronary lesions. Understanding this can help practitioners evaluate which lesions could induce myocardial ischaemia and, thus, decide which vessels require urgent revascularisation. Non-hyperaemic physiology-based indices, such as instantaneous wave-free ratio (iFR), provide valid alternatives to FFR. While FFR and iFR are recommended by international guidelines in stable CAD, there is ongoing discussion regarding the role of physiology in patients with ACS and multivessel disease (MVD); growing evidence supports FFR use in the latter. Compelling findings show FFR-guided complete percutaneous coronary intervention (PCI) can reduce adverse cardiovascular events, mortality, and repeat revascularisations in ACS and MVD patients compared to angiography-based PCI. However, FFR is limited in identifying non-flow-limiting vulnerable plaques, which can disadvantage high-risk patients. Here, integrating coronary physiology assessment with intracoronary imaging in decision-making can improve outcomes and quality of life. Further research into novel physiology-based tools in ACS and MVD is needed. This review aims to highlight the key evidence surrounding the role of FFR and other functional indices in guiding PCI strategy in ACS and MVD patients.

Placental mitochondrial impairment and its association with maternal metabolic dysfunction.

The placenta plays an essential role in pregnancy, leading to proper fetal development and growth. As an organ with multiple physiological functions for both mother and fetus, it is a highly energetic and metabolically demanding tissue. Mitochondrial physiology plays a crucial role in the metabolism of this organ and thus any alteration leading to mitochondrial dysfunction has a severe outcome in the development of the fetus. Pregnancy-related pathological states with a mitochondrial dysfunction outcome include preeclampsia and gestational diabetes mellitus. In this review, we address the role of mitochondrial morphology, metabolism and physiology of the placenta during pregnancy, highlighting the roles of the cytotrophoblast and syncytiotrophoblast. We also describe the relationship between preeclampsia, gestational diabetes, gestational diabesity and pre-pregnancy maternal obesity with mitochondrial dysfunction.

Stress-induced increase in heart-rate during sleep as an indicator of PTSD risk among combat soldiers.

Discerning the differential contribution of sleep behavior and sleep physiology to the subsequent development of posttraumatic-stress-disorder (PTSD) symptoms following military operational service among combat soldiers. Longitudinal design with three measurement time points: during basic training week (T1), during intensive stressed training week (T2), and following military operational service (T3). Participating soldiers were all from the same unit, ensuring equivalent training schedules and stress exposures. During measurement weeks soldiers completed the Depression Anxiety and Stress Scale (DASS) and the PTSD Checklist for DSM-5 (PCL-5). Sleep physiology (sleep heart-rate) and sleep behavior (duration, efficiency) were monitored continuously in natural settings during T1 and T2 weeks using wearable sensors. Repeated measures ANOVA revealed a progressive increase in PCL-5 scores from T1 and T2 to T3, suggesting an escalation in PTSD symptom severity following operational service. Hierarchical linear regression analysis uncovered a significant relation between the change in DASS stress scores from T1 to T2 and subsequent PCL-5 scores at T3. Incorporating participants' sleep heart-rate markedly enhanced the predictive accuracy of the model, with increased sleep heart-rate from T1 to T2 emerging as a significant predictor of elevated PTSD symptoms at T3, above and beyond the contribution of DASS stress scores. Sleep behavior did not add to the accuracy of the model. Findings underscore the critical role of sleep physiology, specifically elevated sleep heart-rate following stressful military training, in indicating subsequent PTSD risk following operational service among combat soldiers. These findings may contribute to PTSD prediction and prevention efforts.

Corrigendum: Disentangling brain PrPC proteoforms and their roles in physiology and disease.

Corrigendum: Disentangling brain PrPC proteoforms and their roles in physiology and disease.

Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study.

Epidemiological studies have linked low birth weight to psychiatric disorders, including substance use disorders. Genomic analyses suggest a role of placental physiology on psychiatric risk. We investigated whether this association is causally related to impaired trophoblast function. We conducted a two-sample summary-data Mendelian randomization study using as instrumental variables those genetic variants strongly associated with birth weight, whose effect is exerted through the fetal genome, and are located near genes with differential expression in trophoblasts. Eight psychiatric and substance use disorders with >10,000 samples were included as outcomes. The inverse variance weighted method was used as the main analysis and several sensitivity analyses were performed for those significant results. The inverse variance weighted estimate, based on 14 instrumental variables, revealed an association, after correction for multiple tests, between birth weight and broadly defined depression (β = -0.165, 95% CI = -0.282 to -0.047, P = 0.0059). Sensitivity analyses revealed the absence of heterogeneity in the effect of instrumental variables, confirmed by leave-one-out analysis, MR_Egger intercept, and MR_PRESSO. The effect was consistent using robust methods. Reverse causality was not detected. The effect was specifically linked to genetic variants near genes involved in trophoblast physiology instead of genes with fetal effect on birth weight or involved in placenta development. Impaired trophoblast functioning, probably leading to reduced fetal brain oxygen and nutrient supply, is causally related to broadly defined depression. Considering the therapeutic potential of some agents to treat fetal growth restriction, further research on the effect of trophoblast physiology on mental disorders may have future implications in prevention.

The role of membrane physiology in sHSP Lo18-lipid interaction and lipochaperone activity

To cope with environmental stresses, organisms, including lactic acid bacteria such as O. oeni, produce stress proteins called HSPs. In wine, O. oeni is constantly confronted by stress affecting its membrane fluidity. To survive through in these deleterious conditions, O. oeni synthesizes Lo18, a unique, small HSP which acts as a molecular chaperone and a lipochaperone. The molecular mechanism underlying its lipochaperone activity, particularly regarding membrane lipid composition, remains poorly understood. In this context, Lo18 lipochaperone activity and the associated modification in protein structure were studied during interaction with different liposomes from O. oeni cultures representing unstressed, stressed and stressed-adapted physiological states. The results showed that the presence of the membrane (whatever its nature) induces a modification of Lo18’s structure. Also, the presence of oleic acid and/or phosphatidylglycerol is important to favor Lo18-membrane interaction, allowing lipochaperone activity. This research enhances understanding of sHSP-membrane interactions in bacterial systems.

Characterizing patterns of diffusion tensor imaging variance in aging brains.

As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Here, we characterize the role of physiology, subject compliance, and the interaction of the subject with the scanner in the understanding of DTI variability, as modeled in the spatial variance of derived metrics in homogeneous regions. We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging, with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess the variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related ( ) to FA variance in the cuneus and occipital gyrus, but negatively ( ) in the caudate nucleus. Males show significantly ( ) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated ( ) with a decrease in FA variance. Head motion increases during the rescan of DTI ( mm per volume). The effects of each covariate on DTI variance and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.

Role of Coronary Physiology in the Modern Catheterisation Lab

Over the past two decades, invasive coronary physiology assessment has advanced significantly. Despite the proven prognostic significance provided by invasive physiological assessment of lesions by means of fractional flow reserve or adenosine-free non-hyperaemic pressure ratios, challenges in clinical practice hinder widespread adoption and limit additional value for optimising percutaneous coronary intervention decisions. Despite notable progress, uncertainties persist, emphasising the need for further research to establish a single numerical parameter in the diagnosis of a functionally significant disease, clarify the impact of longitudinal vessel analysis, and support the relevance of pressure indices in post-intervention optimisation.

Shear stress preconditioning and microbubble flow pattern modulate ultrasound-assisted plasma membrane permeabilization

The recent and exciting success of anti-inflammatory therapies for ischemic heart disease (e.g. atherosclerosis) is hindered by the lack of site-specific and targeted therapeutic deposition. Microbubble-mediated focused ultrasound, which uses circulating, lipid-encapsulated intravascular microbubbles to locally enhance endothelial permeability, offers an exciting approach. Atherosclerotic plaques preferentially develop in regions with disturbed blood flow, and microbubble-endothelial cell membrane interactions under such flow conditions are not well understood. Here, using an acoustically-coupled microscopy system, endothelial cells were sonicated (1 MHz, 20 cycle bursts, 1 ms PRI, 4 s duration, 300 kPa peak-negative pressure) under perfusion with Definity™ bubbles to examine microbubble-mediated endothelial permeabilization under a range of physiological conditions. Endothelial preconditioning under prolonged shear influenced physiology and the secretome, inducing increased expression of pro-angiogenesis analytes, decreasing levels of pro-inflammatory ones, and increasing the susceptibility of ultrasound therapy. Ultrasound treatment efficiency was positively correlated with concentrations of pro-angiogenic cytokines (e.g. VEGF-A, EGF, FGF-2), and negatively correlated with pro-inflammatory chemokines (e.g. MCP-1, GCP-2, SDF-1). Furthermore, ultrasound therapy under non-reversing pulsatile flow (∼4–8 dyne/cm2, 0.5–1 Hz) increased permeabilization up to 2.4-fold compared to shear-matched laminar flow, yet treatment under reversing oscillatory flow resulted in more heterogeneous modulation. This study provides insight into the role of vascular physiology, including endothelial biology, into the design of a localized ultrasound drug delivery system for ischemic heart disease.

Drp1: Focus on Diseases Triggered by the Mitochondrial Pathway.

Drp1 (Dynamin-Related Protein 1) is a cytoplasmic GTPase protein encoded by the DNM1L gene that influences mitochondrial dynamics by mediating mitochondrial fission processes. Drp1 has been demonstrated to play an important role in a variety of life activities such as cell survival, proliferation, migration, and death. Drp1 has been shown to play different physiological roles under different physiological conditions, such as normal and inflammation. Recently studies have revealed that Drp1 plays a critical role in the occurrence, development, and aggravation of a series of diseases, thereby it serves as a potential therapeutic target for them. In this paper, we review the structure and biological properties of Drp1, summarize the biological processes that occur in the inflammatory response to Drp1, discuss its role in various cancers triggered by the mitochondrial pathway and investigate effective methods for targeting Drp1 in cancer treatment. We also synthesized the phenomena of Drp1 involving in the triggering of other diseases. The results discussed herein contribute to our deeper understanding of mitochondrial kinetic pathway-induced diseases and their therapeutic applications. It is critical for advancing the understanding of the mechanisms of Drp1-induced mitochondrial diseases and preventive therapies.

Finding the Optimal Strategy for Nonculprit Revascularization in Acute Myocardial Infarction: The Role of Angiography-Derived Physiology.

Finding the Optimal Strategy for Nonculprit Revascularization in Acute Myocardial Infarction: The Role of Angiography-Derived Physiology.

Predictive Role of Acute Physiology and Chronic Health Evaluation II (APACHE II) in Patients With Peritonitis at the National Hospital Abuja.

A validated tool may facilitate assessing the severity of peritonitis among surgical patients. This study evaluates the predictive role of Acute Physiology and Chronic Health Evaluation II (APACHE II) in the surgical outcomes of patients managed for peritonitis in Abuja. This is a prospective study of consecutive adult patients managed for peritonitis by the general surgery unit of National Hospital Abuja (NHA) over a 19-month period (September 2020 through March 2022). Patient characteristics and treatment outcomes were recorded in a structured proforma and analyzed using SPSS Statistics version 25 (IBM Corp., Released 2017; IBM SPSS Statistics for Windows, Version 25.0; Armonk, NY: IBM Corp.). The accuracy, sensitivity, specificity, and threshold of APACHE II were derived from the receiver operating characteristic (ROC) curve analysis and its coordinates. There were 54 patients with peritonitis during the study period, with a male-to-female ratio of 2.6:1. This study's mortality and morbidity rates were 13.0% and 63.0%, respectively. The APACHE II score at admission was positively correlated with the likelihood of postoperative mortality, morbidity, number of postoperative complications, ICU admission, and length of hospital admission. The average APACHE II score of patients in this study was 7.1±5.2. APACHE II best-predicted mortality by the ROC curve at a threshold point of 9 (sensitivity of 85.7%, specificity of 70.2%, the accuracy of 86.8%, P-value 0.002). At a threshold score of 6, APACHE II was significantly associated with the occurrence of postoperative morbidity (sensitivity of 74.3%, specificity of 73.7%, accuracy of 75.2%, P-value = 0.043). This study confirms that the APACHE II score at admission can predict the outcome of surgery within the first 30 days post-surgery among adult patients who had peritonitis at NHA.

Redefining Classical Theory of Humours (Akhlat) with Emphasis on Khilt-e-Sauda (Black Bile) Through its Physiological Role

Background: According to Hippocrates, Akhlat is of four types, i.e., Dam (Blood), Balgham (Phlegm), Safra (Yellow Bile), and Sauda (Black Bile). The correct proportion of these fluids in the body, in terms of quality and quantity, leads to health, while their irregular distribution leads to diseases. The argument presented in this paper will encompass both Tabayi and Ghair Tabayi Sauda. Objective: However, in light of recent advances in the area of molecular biology and biochemistry of the human body, we aim to discuss Sauda as a Khilt in the context of human physiology. We propose that the chemico-biological / physiological role of the molecule rather than its structure will define its placement in Khilt-e-Sauda. Conclusion: Chemico/biological role of the molecule may change with the physiological context, and hence the placement of the molecule previously included in the Khilt-e-Sauda, may or may not remain in that categorization at that point in time in that physiological state.

Thermal tolerance does not explain the altitudinal segregation of lowland and alpine aquatic insects

Elevation gradients provide powerful study systems for examining the influence of environmental filters in shaping species assemblages. High-mountain habitats host specific high-elevation assemblages, often comprising specialist species adapted to endure pronounced abiotic stress, while such harsh conditions prevent lowland species from colonizing or establishing. While thermal tolerance may drive the altitudinal segregation of ectotherms, its role in structuring aquatic insect communities remains poorly explored. This study investigates the role of thermal physiology in shaping the current distribution of high-mountain diving beetles from the Sierra Nevada Iberian mountain range and closely related lowland species. Cold tolerance of five species from each altitudinal zone was measured estimating the supercooling point (SCP), lower lethal temperature (LLT) and tolerance to ice enclosure, while heat tolerance was assessed from the heat coma temperature (HCT). Alpine species exhibited wider fundamental thermal niches than lowland species, likely associated with the broader range of climatic conditions in high-mountain areas. Cold tolerance did not seem to prevent lowland species from colonizing higher elevations, as most studied species were moderately freeze-tolerant. Therefore, fundamental thermal niches seem not to fully explain species segregation along elevation gradients, suggesting that other thermal tolerance traits, environmental factors, and biotic interactions may also play important roles.

Amyloid precursor protein combinatorial phosphorylation code regulates AMPA receptor removal during distinct forms of synaptic plasticity

Synaptic plasticity is essential for memory encoding and stabilization of neural network activity. Plasticity is impaired in neurodegenerative conditions including Alzheimer disease (AD). A central factor in AD is amyloid precursor protein (APP). Previous studies have suggested APP involvement in synaptic plasticity, but physiological roles of APP are not well understood. Here, we identified combinatorial phosphorylation sites within APP that regulate AMPA receptor trafficking during different forms of synaptic plasticity. Dual phosphorylation sites at threonine-668/serine-675 of APP promoted endocytosis of the GluA2 subunit of AMPA receptors during homeostatic synaptic plasticity. APP was also required for GluA2 internalization during NMDA receptor-dependent long-term depression, albeit via a distinct pair of phosphoresidues at serine-655/threonine-686. These data implicate APP as a central gate for AMPA receptor internalization during distinct forms of plasticity, unlocked by specific combinations of phosphoresidues, and suggest that APP may serve broad functions in learning and memory.

Phosphorylation of tau protein based on the activity of kinases and phosphatases in various forms of synaptic plasticity.

The aim of this study is to show the relationship between the change in the strengthening of synaptic plasticity and tau phosphorylation and tau-kinases and phosphatase. The averages of the field excitatory-postsynaptic potential (fEPSP) and population spike (PS) in the last 5 min were used as a measure of LTP, LTD and MP. Total and phosphorylated levels of tau, kinases and phosphatases were evaluated by western blot and mRNA levels were evaluated by RT-qPCR. The stimulation of synapses by HFS and LFS+HFS increased the phosphorylation of total-tau and phospho-tau at the Thr181, Ser202/Thr205, Ser396 and Ser416 residues, and these were accompanied by increased enzymatic activity of Akt, ERK1/2. Theincreased phosphorylation of tau may mediate maintenance of LTP. If the increase in phosphorylation of tau cannot be prevented, together with inhibition of the subsequent LTP, this may indicate that the physiological role of hyperphosphorylated tau in synaptic plasticity may extend to pathological processes.

MEDICAL PHYSIOLOGY: ADVANCEMENTS IN TEACHING APPROACHES AT MEDICAL UNIVERSITIES

This article addresses the pressing issues of training modern medical and dental doctors as well as masters in biology at higher medical institutions, examining contemporary theoretical and practical approaches to integrating medical physiology as a fundamental medical amd biological discipline. It delves into current challenges in teaching physiology within the modern educational landscape, particularly focusing on the Department of Physiology at the Poltava State Medical University. This discipline is delivered by the Department of Physiology for students of the second (Master) level of higher education in the field "Healthcare" and "Biology". Physiology is a cornerstone discipline that fosters interdisciplinary integration in medical education, bridging theoretical knowledge with practical application in clinical settings. Emphasizing a practically oriented teaching principle, the article underscores the pivotal role of physiology in preparing students for clinical practice. The department adopts a comprehensive approach, developing and updating educational materials and manuals, including laboratory work with detailed descriptions of physiological research methods. Highlighting the department's achievements, it mentions their contribution to the first Ukrainian translation of the renowned physiology textbook "Medical Physiology” by Guyton and Hall in two volumes. It concludes by stressing the importance of enhancing the quality of education in medical institutions through continuous improvements in teaching practices, integration of advanced scientific developments and technologies, and the provision of modern educational resources and facilities, particularly in the field of physiology, which serves as the theoretical backbone of clinical medicine.

PRACTICAL APPROACH IN DELIVERING THEME "AUTONOMIC REFLEXES AND THEIR CLINICAL APPLICATION" AT THE DEPARTMENT OF PHYSIOLOGY, POLTEVE STATE MEDICAL UNIVERSITY

In the system of higher medical education, physiology is a fundamental discipline and occupies an important place in the system of training highly qualified medical specialists. In the system of higher medical education, physiology stands as a cornerstone discipline, holding a pivotal role in shaping the competencies of future medical professionals. The scientific and pedagogical staff at the Department of Physiology, Poltava State Medical University, is dedicated to nurturing students' capacity to analyze and synthesize both theoretical and practical knowledge, laying the groundwork for clinical acumen in future specialists. This article presents a hands-on approach to teaching the topic "Autonomic Reflexes and Their Clinical Applications" within the contemporary educational landscape, targeting second-year master's and first-year bachelor's students. Highlighting the practical significance of this topic in the future medical practice, it underscores how mastering autonomic reflexes equips students with the skills to influence internal organ activity and administer emergency medical care. Such an approach not only fosters student engagement with the subject matter but also cultivates a deeper appreciation for physiology as a whole. The article outlines the instructional principles, spanning from theoretical discourse to practical exercises, emphasizing the integral role of physiology in higher medical education. By advocating for the study of physiology as a foundational science, the article underscores its role in fostering interdisciplinary integration and shaping clinical reasoning—an essential aspect of quality medical training in today's educational landscape.

Biochemical and structural characterization reveals Rv3400 codes for β-phosphoglucomutase in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) adapt to various host environments and utilize a variety of sugars and lipids as carbon sources. Among these sugars, maltose and trehalose, also play crucial role in bacterial physiology and virulence. However, some key enzymes involved in trehalose and maltose metabolism in Mtb are not yet known. Here we structurally and functionally characterized a conserved hypothetical gene Rv3400. We determined the crystal structure of Rv3400 at 1.7 Å resolution. The crystal structure revealed that Rv3400 adopts Rossmann fold and shares high structural similarity with haloacid dehalogenase family of proteins. Our comparative structural analysis suggested that Rv3400 could perform either phosphatase or pyrophosphatase or β-phosphoglucomutase (β-PGM) activity. Using biochemical studies, we further confirmed that Rv3400 performs β-PGM activity and hence, Rv3400 encodes for β-PGM in Mtb. Our data also confirm that Mtb β-PGM is a metal dependent enzyme having broad specificity for divalent metal ions. β-PGM converts β-D-glucose-1-phosphate to β-D-glucose-6-phosphate which is required for the generation of ATP and NADPH through glycolysis and pentose phosphate pathway, respectively. Using site directed mutagenesis followed by biochemical studies, we show that two Asp residues in the highly conserved DxD motif, D29 and D31, are crucial for enzyme activity. While D29A, D31A, D29E, D31E and D29N mutants lost complete activity, D31N mutant retained about 30% activity. This study further helps in understanding the role of β-PGM in the physiology of Mtb.