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ObjectiveThis study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.Research design and methodsParticipants age ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported outcomes, and the technology acceptance model were assessed to evaluate the intervention's effectiveness and acceptance.ResultsOut of 117 initial participants, 97 completed the study. Significant improvements were observed in the intervention group compared with the control group in gait performance (stride time at dual-task and fast walking), physical activity (stand to walk and sit to stand), quality of life, plantar numbness, and cognitive function after 12 weeks. The intervention group showed that magnitudes of improvement on gait performance and physical activity metrics were associated with enhancements in quality of life and cognitive function, respectively. The intervention group also reported higher usefulness and usage satisfaction, with a greater willingness to continue using E-Stim at home.ConclusionsThe 12-week intradialytic E-Stim intervention is a feasible and effective method to enhance gait performance, physical activity level, cognitive function, and other patient-reported outcomes in patients undergoing hemodialysis, representing a practical, low-risk therapy option for those unable to engage in traditional exercise programs.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used omic assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

Microglia-mediated inflammation exerts adverse effects in ischemic stroke and in neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the voltage-gated potassium channel Kv1.3 is required for microglia activation. Both genetic deletion and pharmacological inhibition of Kv1.3 are effective in reducing microglia activation and the associated inflammatory responses, as well as in improving neurological outcomes in animal models of AD and ischemic stroke. Here we sought to elucidate the molecular mechanisms underlying the therapeutic effects of Kv1.3 inhibition, which remain incompletely understood. Using a combination of whole-cell voltage-clamp electrophysiology and quantitative PCR (qPCR), we first characterized a stimulus-dependent differential expression pattern for Kv1.3 and P2X4, a major ATP-gated cationic channel, both in vitro and in vivo. We then demonstrated by whole-cell current-clamp experiments that Kv1.3 channels contribute not only to setting the resting membrane potential but also play an important role in counteracting excessive membrane potential changes evoked by depolarizing current injections. Similarly, the presence of Kv1.3 channels renders microglia more resistant to depolarization produced by ATP-mediated P2X4 receptor activation. Inhibiting Kv1.3 channels with ShK-223 completely nullified the ability of Kv1.3 to normalize membrane potential changes, resulting in excessive depolarization and reduced calcium transients through P2X4 receptors. Our report thus links Kv1.3 function to P2X4 receptor-mediated signaling as one of the underlying mechanisms by which Kv1.3 blockade reduces microglia-mediated inflammation. While we could confirm previously reported differences between males and females in microglial P2X4 expression, microglial Kv1.3 expression exhibited no gender differences in vitro or in vivo. MAIN POINTS: The voltage-gated K+ channel Kv1.3 regulates microglial membrane potential. Inhibition of Kv1.3 depolarizes microglia and reduces calcium entry mediated by P2X4 receptors by dissipating the electrochemical driving force for calcium.

The CaFe12O19/MnFe2O4 composites with the hard (CaFe12O19) and soft (MnFe2O4) magnetic phases, were prepared by chemical co-precipitation method. The prepared composites were calcined at three different temperatures to form different phases. The structural, morphological, and magnetic properties of composite were analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), room temperature vibrational sample magnetometer (VSM), and transmission electron microscopy (TEM). The presence of the hard and soft phases has been confirmed without any secondary phase from XRD analysis, indicating the formation of composite. The crystallite size is found to be in the range of 24-44 nm calculated by Scherrer's formula. The TEM revealed hexagonal platelets of CaFe12O19 with spinel MnFe2O4 particles with an average particle size of 48 nm formed at the surface of the CaFe12O19/ MnFe2O4 composite. The room temperature magnetic properties of composite were evaluated by employing VSM. The magnetic measurements have displayed enhancement in coercivity and magnetization for CaFe12O19/MnFe2O4, indicating that the composite possessed excellent exchange coupling. The composite's enhanced energy product ((BH)max) made it highly promising for biomedical applications such as hyperthermia. The exchange-spring coupled magnetic composite was coated with dextran to make it biocompatible, which is necessary for hyperthermia applications. The coating was confirmed using Fourier transform infrared spectroscopy (FTIR). Cytotoxicity tests on Vero cell lines showed that the coated composites had an excellent (>95%) cell survival rate. The hyperthermia heating of composite was measured for different concentrations of composite (0.25, 0.5, 1, 2, and 4 mg/mL) from which specific loss power (SLP) was calculated. From these SLP values, the optimized concentration was identified. [ABSTRACT FROM AUTHOR]