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NeuroImage Jun 2020Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations...
Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations between distant brain regions. Here, we investigated whether such "physiological networks"-sets of segregated brain regions that exhibit similar responses following slow changes in systemic physiology-resemble patterns associated with large-scale networks typically attributed to remotely synchronized neuronal activity. By analyzing a large group of subjects from the 3T Human Connectome Project (HCP) database, we demonstrate brain-wide and noticeably heterogenous dynamics tightly coupled to either respiratory variation or heart rate changes. We show, using synthesized data generated from physiological recordings across subjects, that these physiologically-coupled fluctuations alone can produce networks that strongly resemble previously reported resting-state networks, suggesting that, in some cases, the "physiological networks" seem to mimic the neuronal networks. Further, we show that such physiologically-relevant connectivity estimates appear to dominate the overall connectivity observations in multiple HCP subjects, and that this apparent "physiological connectivity" cannot be removed by the use of a single nuisance regressor for the entire brain (such as global signal regression) due to the clear regional heterogeneity of the physiologically-coupled responses. Our results challenge previous notions that physiological confounds are either localized to large veins or globally coherent across the cortex, therefore emphasizing the necessity to consider potential physiological contributions in fMRI-based functional connectivity studies. The rich spatiotemporal patterns carried by such "physiological" dynamics also suggest great potential for clinical biomarkers that are complementary to large-scale neuronal networks.
Topics: Adult; Brain; Connectome; Female; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Respiration; Rest
PubMed: 32145437
DOI: 10.1016/j.neuroimage.2020.116707 -
Frontiers in Digital Health 2023Healthcare is increasingly fragmented, resulting in escalating costs, patient dissatisfaction, and sometimes adverse clinical outcomes. Strategies to decrease healthcare...
Healthcare is increasingly fragmented, resulting in escalating costs, patient dissatisfaction, and sometimes adverse clinical outcomes. Strategies to decrease healthcare fragmentation are therefore attractive from payer and patient perspectives. In this commentary, a patient-centered smart phone application called Virtual Twin for Healthcare Management (VTHM) is proposed, including its organizational layout, basic functionality, and potential clinical applications. The platform features a virtual twin hub that displays the body and its health data. This is a physiologically based human model that is "virtualized" for the patient based on their unique genetic, molecular, physiological, and disease characteristics. The spokes of the system are a full service and interoperable electronic-health record, accessible to healthcare providers with permission on any device with internet access. Theoretical case studies based on real scenarios are presented to show how VTHM could potentially improve patient care and clinical efficiency. Challenges that must be overcome to turn VTHM into reality are also briefly outlined. Notably, the VTHM platform is designed to operationalize current and future precision medicine initiatives, such as access to molecular diagnostic results, pharmacogenomics-guided prescribing, and model-informed precision dosing.
PubMed: 37781454
DOI: 10.3389/fdgth.2023.1246659 -
The FEBS Journal May 2023Serine proteases (SPs) constitute a very important family of enzymes, both physiologically and pathologically. The effects produced by these proteins have been explained... (Review)
Review
Serine proteases (SPs) constitute a very important family of enzymes, both physiologically and pathologically. The effects produced by these proteins have been explained by their proteolytic activity. However, the discovery of pharmacologically active SP molecules that show no enzymatic activity, as the so-called pseudo SPs or SP homologs (SPHs), has exposed a profoundly neglected possibility of nonenzymatic functions of these SP molecules. In this review, the most thoroughly described SPHs are presented. The main physiological domains in which SPHs operate appear to be in reproduction, embryonic development, immune response, host defense, and hemostasis. Hitherto unexplained actions of SPs should therefore be considered also as the result of the ligand-like attributes of SPs. The gain of a novel function by an SPH is a consequence of specific amino acid replacements that have resulted in a novel interaction interface or a 'catalytic trap'. Unraveling the SP/SPH interactome will provide a description of previously unknown physiological functions of SPs/SPHs, aiding the creation of innovative medical approaches.
Topics: Serine; Serine Proteases; Serine Endopeptidases; Immunity
PubMed: 35032346
DOI: 10.1111/febs.16355 -
International Journal of Molecular... Aug 2021Peptides present in foods are involved in nutritional functions by supplying amino acids; sensory functions related to taste or solubility, emulsification, etc.; and... (Review)
Review
Peptides present in foods are involved in nutritional functions by supplying amino acids; sensory functions related to taste or solubility, emulsification, etc.; and bioregulatory functions in various physiological activities. In particular, peptides have a wide range of physiological functions, including as anticancer agents and in lowering blood pressure and serum cholesterol levels, enhancing immunity, and promoting calcium absorption. Soy protein can be partially hydrolyzed enzymatically to physiologically active soy (or soybean) peptides (SPs), which not only exert physiological functions but also help amino acid absorption in the body and reduce bitterness by hydrolyzing hydrophobic amino acids from the C- or N-terminus of soy proteins. They also possess significant gel-forming, emulsifying, and foaming abilities. SPs are expected to be able to prevent and treat atherosclerosis by inhibiting the reabsorption of bile acids in the digestive system, thereby reducing blood cholesterol, low-density lipoprotein, and fat levels. In addition, soy contains blood pressure-lowering peptides that inhibit angiotensin-I converting enzyme activity and antithrombotic peptides that inhibit platelet aggregation, as well as anticancer, antioxidative, antimicrobial, immunoregulatory, opiate-like, hypocholesterolemic, and antihypertensive activities. In animal models, neuroprotective and cognitive capacity as well as cardiovascular activity have been reported. SPs also inhibit chronic kidney disease and tumor cell growth by regulating the expression of genes associated with apoptosis, inflammation, cell cycle arrest, invasion, and metastasis. Recently, various functions of soybeans, including their physiologically active functions, have been applied to health-oriented foods, functional foods, pharmaceuticals, and cosmetics. This review introduces some current results on the role of bioactive peptides found in soybeans related to health functions.
Topics: Animals; Humans; Peptides; Phytochemicals; Soybean Proteins; Glycine max
PubMed: 34445273
DOI: 10.3390/ijms22168570 -
Journal of Clinical Medicine Oct 2021Articulating a satisfactory definition of a disease is surprisingly difficult. Despite the alarming individual, societal and economic burden of chronic obstructive... (Review)
Review
Articulating a satisfactory definition of a disease is surprisingly difficult. Despite the alarming individual, societal and economic burden of chronic obstructive pulmonary disease (COPD), diagnosis is still largely based on a physiologically dominated disease conception, with spirometrically determined airflow limitation as a cardinal feature of the disease. The diagnostic inaccuracy and insensitivity of this physiological disease definition is reviewed considering scientific developments of imaging of the respiratory system in particular. Disease must be approached as a fluid concept in response to new scientific and medical discoveries, but labelling as well as mislabelling someone as diseased, will have enormous individual, social and financial implications. Nosology of COPD urgently needs to dynamically integrate more sensitive diagnostic procedures to detect the breadth of abnormalities early in the disease process. Integration of broader information for the identification of abnormalities in the respiratory system is a cornerstone for research models of underlying pathomechanisms to create a breakthrough in research.
PubMed: 34682780
DOI: 10.3390/jcm10204660 -
Molecular Aspects of Medicine Dec 2022Biomedical research often focuses on properties that differentiate between diseased and healthy tissue; one of the current focuses is elevated expression and altered... (Review)
Review
Biomedical research often focuses on properties that differentiate between diseased and healthy tissue; one of the current focuses is elevated expression and altered localisation of proteases. Among these proteases, dysregulation of cysteine cathepsins can frequently be observed in inflammation-associated diseases, which tips the functional balance from normal physiological to pathological manifestations. Their overexpression and secretion regularly exhibit a strong correlation with the development and progression of such diseases, making them attractive pharmacological targets. But beyond their mostly detrimental role in inflammation-associated diseases, cysteine cathepsins are physiologically highly important enzymes involved in various biological processes crucial for maintaining homeostasis and responding to different stimuli. Consequently, several challenges have emerged during the efforts made to translate basic research data into clinical applications. In this review, we present both physiological and pathological roles of cysteine cathepsins and discuss the clinical potential of cysteine cathepsin-targeting strategies for disease management and diagnosis.
Topics: Humans; Cathepsins; Cysteine; Inflammation
PubMed: 36283280
DOI: 10.1016/j.mam.2022.101150 -
International Journal of Molecular... May 2021Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and... (Review)
Review
Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and tortuous retinal blood vessels, and retinal or vitreous hemorrhages that may lead to retinal detachment, vision impairment and blindness. Compared with other neovascular diseases, ROP is unique because of ongoing and concurrent physiological and pathological angiogenesis in the developing retina. While the disease is currently treated by laser or cryotherapy, anti-vascular endothelial growth factor (VEGF) agents have been extensively investigated but are not approved in the U.S. because of safety concerns that they negatively interfere with physiological angiogenesis of the developing retina. An ideal therapeutic strategy would selectively inhibit pathological but not physiological angiogenesis. Our group recently described a novel strategy that selectively and safely alleviates pathological RNV in animal models of ROP by targeting secretogranin III (Scg3), a disease-restricted angiogenic factor. The preclinical profile of anti-Scg3 therapy presents a high potential for next-generation disease-targeted anti-angiogenic therapy for the ROP indication. This review focuses on retinal vessel development in neonates, the pathogenesis of ROP and its underlying molecular mechanisms, including different animal models, and provides a summary of current and emerging therapies.
Topics: Animals; Animals, Newborn; Chromogranins; Humans; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxygen; Retina; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A
PubMed: 34062733
DOI: 10.3390/ijms22094809 -
Journal of Science and Medicine in Sport Jun 2023Physiological and psychological stressors can degrade soldiers' readiness and performance during military training and operational environments. Integrative and holistic... (Review)
Review
OBJECTIVES
Physiological and psychological stressors can degrade soldiers' readiness and performance during military training and operational environments. Integrative and holistic assessments of biomarkers across diverse human performance optimization domains during multistressor training can be leveraged to provide actionable insight to military leadership regarding service member health and readiness.
DESIGN/METHOD
A broad categorization of biomarkers, to include biochemical measures, bone and body composition, psychometric assessments, movement screening, and physiological load can be incorporated into robust analytical pipelines for understanding the complex factors that impact military human performance.
RESULTS
In this perspective commentary we overview the rationale, selection, and methodologies for monitoring biomarker domains that are relevant to military research and specifically highlight methods that have been incorporated in a research program funded by the Office of Naval Research, Code 34 Biological and Physiological Monitoring and Modeling of Warfighter Performance.
CONCLUSIONS
The integration of screening and continuous monitoring methodologies via robust analytical approaches will provide novel insight for military leaders regarding health, performance, and readiness outcomes during multistressor military training.
Topics: Humans; Physical Fitness; Military Personnel; Stress, Psychological; Military Health; Monitoring, Physiologic
PubMed: 36631385
DOI: 10.1016/j.jsams.2022.12.005 -
Biosensors Sep 2023With the innovation of wearable technology and the rapid development of biosensors, wearable biosensors based on flexible textile materials have become a hot topic. Such... (Review)
Review
With the innovation of wearable technology and the rapid development of biosensors, wearable biosensors based on flexible textile materials have become a hot topic. Such textile-based wearable biosensors promote the development of health monitoring, motion detection and medical management, and they have become an important support tool for human healthcare monitoring. Textile-based wearable biosensors not only non-invasively monitor various physiological indicators of the human body in real time, but they also provide accurate feedback of individual health information. This review examines the recent research progress of fabric-based wearable biosensors. Moreover, materials, detection principles and fabrication methods for textile-based wearable biosensors are introduced. In addition, the applications of biosensors in monitoring vital signs and detecting body fluids are also presented. Finally, we also discuss several challenges faced by textile-based wearable biosensors and the direction of future development.
Topics: Humans; Biosensing Techniques; Wearable Electronic Devices; Body Fluids; Delivery of Health Care; Textiles; Monitoring, Physiologic
PubMed: 37887102
DOI: 10.3390/bios13100909