Pflugers Archiv : European journal of physiology最新文献

The rapid integration of artificial intelligence (AI) into surgical practice necessitates a comprehensive evaluation of its applications, challenges, and physiological impact. This systematic review synthesizes current AI applications in surgery, with a particular focus on machine learning (ML) and its role in optimizing preoperative planning, intraoperative decision-making, and postoperative patient management. Using PRISMA guidelines and PICO criteria, we analyzed key studies addressing AI's contributions to surgical precision, outcome prediction, and real-time physiological monitoring. While AI has demonstrated significant promise-from enhancing diagnostics to improving intraoperative safety-many surgeons remain skeptical due to concerns over algorithmic unpredictability, surgeon autonomy, and ethical transparency. This review explores AI's physiological integration into surgery, discussing its role in real-time hemodynamic assessments, AI-guided tissue characterization, and intraoperative physiological modeling. Ethical concerns, including algorithmic opacity and liability in high-stakes scenarios, are critically examined alongside AI's potential to augment surgical expertise. We conclude that longitudinal validation, improved AI explainability, and adaptive regulatory frameworks are essential to ensure safe, effective, and ethically sound integration of AI into surgical decision-making. Future research should focus on bridging AI-driven analytics with real-time physiological feedback to refine precision surgery and patient safety strategies.

Cerebrocortical neurons receive glutamatergic inputs via thalamocortical projections, and their activities are simultaneously controlled by GABAergic interneurons. Few studies have demonstrated the difference in the amplitude of evoked excitatory postsynaptic currents (EPSCs) via thalamocortical projections onto glutamatergic excitatory (ENs) and GABAergic inhibitory neurons (INs); the strength of excitation among neural subtypes varies among sensory cortices. The present study aimed to reveal the profile of thalamocortical inputs to ENs and inhibitory neurons in the insular cortex (IC) by evaluating the amplitude and latency of EPSCs evoked in the connection from the ventroposteromedial (VPM) thalamic nucleus to the IC. Whole-cell patch-clamp recordings were prepared from ENs, fast-spiking neurons (FSNs), and non-fast-spiking neurons (NFSNs) in the middle layers (layer 4 and adjacent layers) of the IC. Photostimulation-induced EPSCs (pEPSCs) were evoked via the selective activation of thalamocortical axons via optogenetics. All the neuronal subtypes received direct excitatory inputs from the VPM, and pEPSCs recorded from FSNs had the greatest amplitude and shortest latency compared with those recorded from ENs and NFSNs. Under current-clamp conditions, FSNs almost invariably exhibited action potentials responding to photostimulation, whereas ENs and NFSNs often showed the failure of action potential induction. In addition to excitatory inputs, some neurons exhibited pEPSCs followed by outward GABA_A receptor-mediated currents, which curtailed the pEPSC peak and aligned the timing of the action potential to photostimulation. These results suggested that FSNs play a role in the feedforward inhibition of EN activity in the upper layer of the IC. (244 words).

This special issue presents a collection of reviews on the recent advancements and applications of artificial intelligence (AI) in medicine and physiology. The topics covered include digital histopathology, generative AI, explainable AI (XAI), and ethical considerations in AI development and implementation. The reviews highlight the potential of AI to transform medical diagnostics, personalized medicine, and clinical decision making, while also addressing challenges such as data quality, interpretability, and trustworthiness. The contributions demonstrate the growing importance of AI in physiological research and medicine, the need for multi-level ethics approaches in AI development, and the potential benefits of generative AI in medical applications. Overall, this special issue showcases some of the the pioneering aspects of AI in medicine and physiology, covering technical, applicative, and ethical viewpoints, and underlines the remarkable impact of AI on these fields.

The purpose was to investigate the changes in cytosolic Ca²⁺ and force output during post-tetanic potentiation (PTP) during pre-fatigue and during prolonged low-frequency force depression (PLFFD) following fatigue. Intact single myofibers from the flexor digitorum brevis of mice were electrically stimulated to record force (n = 8) and free cytosolic Ca²⁺ concentration ([Ca²⁺]_c) with FURA-2 (n = 6) at 32 °C. Initially, force and [Ca²⁺]_c were measured during brief (350 ms) trains of stimuli at 30, 50, 70, and 200 Hz at ~ 2 s intervals (Force-frequency protocol, FFP). Then, a conditioning stimulus (CS) of six 120 Hz stimuli, separated by ~ 3 s, was used to induce PTP, immediately followed by an FFP. Myofiber fatigue was produced by 150 Hz trains every 3 s until peak force decayed 70% of the initial. Thirty minutes after the fatigue, the CS was repeated to assess the effect of PTP on force and [Ca²⁺]_c during PLFFD. The CS in unfatigued myofibers induced PTP as the submaximal force was enhanced and accompanied by increased peak [Ca²⁺]_c with no change in myofilament Ca²⁺ sensitivity. After fatigue, PLFFD was due to lowered peak [Ca²⁺]_c. Inducing PTP during PLFFD enhanced submaximal force primarily through greater peak [Ca²⁺]_c, mitigating the submaximal force deficits. Despite the impaired force during PLFFD, myofibers remained sensitive to PTP, and this mitigated the submaximal force deficits through increased peak [Ca²⁺]_c without a change in myofilament Ca²⁺ sensitivity. Therefore, force adjustments of intact single myofibers due to activation history are principally accomplished by opposing adjustments in [Ca²⁺]_c.

The prevalence of panic disorder is two to four times higher in women compared to that in men, and hormonal changes during the menstrual cycle play a role in the occurrence of panic attacks. Here, we investigated the effect of the estrous cycle on the ventilatory and behavioral responses to CO₂ in mice. Female mice in proestrus, estrus, metestrus, or diestrus were exposed to 20% CO₂, and their escape behaviors, brain monoamines, and plasma levels of 17β-estradiol (E₂) and progesterone (P₄) were measured. Pulmonary ventilation (V̇_E), oxygen consumption (V̇O₂), and body core temperature (T_B) were also measured during normocapnia followed by CO₂. Females exposed to 20% CO₂ exhibited an escape behavior, but the estrous cycle did not affect this response. Females in all phases of the estrous cycle showed higher V̇_E and lower T_B during hypercapnia. In diestrus, there was an attenuation of CO₂-induced hyperventilation with no change in V̇O₂, whereas in estrus, this response was accompanied by a reduction in V̇O₂. Hypercapnia also increased the concentration of plasma P₄ and central DOPAC, the main dopamine metabolite, in all females. There was an estrous cycle effect on brainstem serotonin, with females in estrus showing a higher concentration than females in the metestrus and diestrus phases. Therefore, our data suggest that hypercapnia induces panic-related behaviors and ventilatory changes that lead to an increase in P₄ secretion in female mice, likely originating from the adrenals. The estrous cycle does not affect the behavioral response but interferes in the ventilatory and metabolic responses to CO₂ in mice.

Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease characterized by renal cysts. It arises from mutations in proteins expressed in part in the primary cilia of renal epithelial cells. One of these, polycystin-2 (PC2), is an ion-conducting channel. To date, ion channels in the cilium have only been characterized in standard normosmolar external solutions, but the osmolality of the renal filtrate bathing the cilia varies widely. Here I report that urine, which better represents the filtrate, activates a large cation-conducting current in the cilia. With defined external solutions, hyperosmolality through addition of urea, NaCl, or D-mannitol activates a similar current. Most but not all of this current is conducted through TRPM4 channels. It is greatly reduced by internal MgATP or 9-phenanthrol, which inhibit TRPM4, or by shRNA knockdown of TRPM4. However, part of the current activated by urea conducts Ca²⁺ through channels that remain to be identified. External hyperosmolality also greatly increases the activity of ciliary PC2 channels; this is the first physiological stimulus identified for these channels. Possibilities are discussed for the mechanisms of channel activation and the roles for these activities in regulatory volume increase and cystogenesis.

The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.

Personalised nutrition (PN) as a new endeavour emerged in the background of the human genome project with the ease to analyse genetic heterogeneity. First commercial offers with recommendations for diet and lifestyle changes, usually based on a few polymorphisms, entered markets soon after the presentation of the human genome blueprint. Although PN has seen many attempts, meanwhile, with the inclusion of other biomedical measures such as microbiome and/or continuous glucose monitoring, scientific assessments of such approaches in various settings revealed limited success. Although personalisation improved general compliance over generic advice, particular benefits in referring to biomedical measures and individual risks did, in most cases, not provide any significant advantage. Moreover, scholars criticised such approaches as of limited impact from a public health perspective by attracting mainly technology-open individuals of high social status and proper financial capabilities. Based on these experiences, new avenues for personalising dietary advice are developed, and those are going beyond pure biomedical data by assessing the entire food environment of the individual with its capabilities and constraints in the given life setting. Embedded into digital environments for data collection but also for bidirectional communication, new possibilities emerge. Artificial intelligence methods allow for the multitude of input data and highly complex decision trees to be derived to customize advice. And that can be delivered on the spot and in time in any language whenever decisions are made on what to buy or what to eat. But systems can also be employed to increase physical activity levels and for the adoption of a more healthy lifestyle in general.

Increased dietary inorganic phosphate (P_i) intake stimulates renal P_i excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary P_i may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary P_i intake over shorter periods are unknown. We studied the effects of a low or high P_i diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000 mg phosphorus equivalent/day) supplemented with either a phosphate binder (low P_i diet) or phosphate capsules (750 mg phosphorus, high P_i diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High P_i intake increased plasma P_i levels and 24-h excretion and decreased urinary calcium excretion. High P_i intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal P_i excretion and reducing calcitriol in healthy young men during steady-state high dietary P_i intake. High dietary P_i intake elevated blood P_i levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum P_i levels are associated with cardiovascular risk in the general population.