Despite its subjectivity, pain has long been addressed primarily within a biomedical framework. This has had the result that the social and psychological aspects of pain have been ignored in both pain research and therapy. However, clinical practice has revealed certain phenomena such as placebo-induced hyperalgesia or hypoalgesia that cannot be explained solely by anatomical structures and physiological processes. The emergence of the “gate control” theory of pain and the development of the biopsychosocial approach provided a conceptual alternative and became the dominant paradigm, leading to the inclusion of cognitive and social factors influencing pain perception in research. This review examines the contributions of social, emotional, and cognitive components to the formation of the experience of pain, including in the clinical context. The analysis systematizes data supporting the need for a comprehensive (biopsychosocial) understanding of the development and modulation of pain. A holistic understanding of the nature of the perception and experience of pain, as well as the mechanisms underlying these processes, will allow the development of more effective non-drug pain management strategies, improve diagnostics, and personalize treatment taking account of patients’ individual psychological characteristics.
We consider a mathematical model of the continuous movement of a spherical robot over an arbitrary uneven surface, as well as a reduced model that excludes slipping and twisting. State-feedback control laws are synthesized to ensure that the robot moves along a given trajectory. The effectiveness of the proposed control laws is demonstrated by computer simulation results. A possible implementation of an electromagnetic drive for generating the robot’s motion is discussed.
The clinical translation of nanoparticles (NPs) for therapeutic applications is hindered significantly by unpredictable biodistribution in diseased patients, which results from the complex interplay between engineered physicochemical properties of NPs and specific changes in the function of biological barriers. This review delves into the multifaceted factors that govern NP biodistribution, highlighting the critical roles of intrinsic NP design, including size, shape, and surface chemistry, along with host-specific physiological and pathological conditions. We overview how these properties can change systemic circulation, organ-specific accumulation, and clearance pathways. The role of surface functionalization in targeted delivery is examined through the lens of altered serum composition, which affects protein corona formation. Particular attention is given to immune response, whether pathogen/antigen-primed, macrophage–monocyte-mediated clearance, compromised biological barriers, and host-specific factors such as sex, age, drug exposure, and gut microbiome. Disease contexts, including cancer and viral infections, are considered to evaluate translational challenges. NP biodistribution is shaped by the interplay between engineered physicochemical properties and disease-associated biological changes. Intrinsic NP characteristics influence systemic circulation, organ-specific accumulation, and clearance pathways. Altered serum composition affects protein corona formation and immune responses, including overactivated or suppressed immune states. Compromised biological barriers, including increased permeability of the blood–brain barrier, enhanced renal excretion, and reduced liver retention, further modify pharmacokinetic profiles. Host-specific variability and pathological conditions introduce additional complexity, creating unique barriers that passive targeting strategies often fail to overcome. Developing a comprehensive grasp of these interrelated mechanisms is crucial for engineering NPs that can translate preclinical results into expected clinical outcomes, ultimately closing the gap between research innovation and patient care.
Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) are classically associated with neuroplasticity, but increasing evidence suggests a broader role for BDNF/TrkB signaling in systemic stress adaptation beyond the central nervous system. Strenuous exercise is a model of functional stress that may become a clinically relevant renal challenge under conditions such as dehydration, heat stress, vascular vulnerability, and repeated exposure. Neuroendocrine stress activation, hemodynamic perturbations, and cytoskeletal instability are key factors that may contribute to glomerular barrier dysfunction in this setting. BDNF biogenesis is complex, and circulating BDNF largely reflects platelet-associated pools and context-dependent release. At the tissue level, BDNF/TrkB signaling can activate actin-regulatory pathways involved in cellular resilience. The podocyte is of particular interest because its actin-dependent architecture functionally parallels that of neurons and is essential for maintenance of the glomerular filtration barrier. Within this framework, BDNF/TrkB signaling may stabilize podocyte actin dynamics, reduce foot process effacement, and attenuate proteinuria. The present review focuses on the brain–kidney axis and the potential renoprotective role of BDNF/TrkB signaling, while highlighting major knowledge gaps regarding BDNF availability to glomerular cells, isoform-specific TrkB actions, and causal inference in humans exposed to repeated exercise-related renal stress. However, current human evidence is insufficient to define the dominant source and delivery route of BDNF to glomerular cells during exercise-related renal stress. Therefore, BDNF/TrkB is discussed here as a candidate modulatory/resilience pathway rather than an established causal driver.
Transcatheter aortic valve implantation (TAVI) is an innovative minimally invasive procedure designed to replace a damaged or narrowed aortic valve. One of important factor is a device selection, which means variety of stent frame types. Bending stiffness of TAVI stent frame provides an ability to withstand external deformation, when it is implanted in the aortic annulus. Patient-specific manufacturing can solve a problem of patient-device sizing and compatibility. For customized manufacturing it is necessary to find a relation between TAVI implant design and strength to avoid post-operative complications. Nevertheless, studies of relations between structure of TAVI stents and their mechanical performance are rare. Thus, eight stent geometries (a–h) including commercial ones (a, b) and own-developed (c–h) were manufactured by filament fused fabrication. Basing on mechanical tests, features of TAVI stent frames, numerical simulations of stent deployment and bending were carried out. Three-point bending was also performed on manufactured stents. The least average value of bending stiffness was shown by models a, e, f, g (0.92–1.09 kN⋅mm2), while the greatest average value was obtained for c model (5.05 kN⋅mm2). Additionally, correlation analysis was performed. To reach bending stiffness of 6 kN⸱mm2, waist position should be 22.4 mm, parameters vertical and horizontal should be 3.4 and 8.7, respectively. The proposed study can help to choose proper TAVI stent frame design basing on demanding stiffness of aorta to provide accurate short- and long-term performance of the prothesis.
