Increased Absorption of Thyroxine in a Murine Model of Hypothyroidism Using Water/CO2 Nanobubbles.

Thyroxine (T4) is a drug extensively utilized for the treatment of hypothyroidism. However, the oral absorption of T4 presents certain limitations. This research investigates the efficacy of CO2 nanobubbles in water as a potential oral carrier for T4 administration to C57BL/6 hypothyroid mice. Following 18 h of fasting, the formulation was administered to the mice, demonstrating that the combination of CO2 nanobubbles and T4 enhanced the drug's absorption in blood serum by approximately 40%. To comprehend this observation at a molecular level, we explored the interaction mechanism through which T4 engages with the CO2 nanobubbles, employing molecular simulations, semi-empirical quantum mechanics, and PMF calculations. Our simulations revealed a high affinity of T4 for the water-gas interface, driven by additive interactions between the hydrophobic region of T4 and the gas phase and electrostatic interactions of the polar groups of T4 with water at the water-gas interface. Concurrently, we observed that at the water-gas interface, the cluster of T4 formed in the water region disassembles, contributing to the drug's bioavailability. Furthermore, we examined how the gas within the nanobubbles aids in facilitating the drug's translocation through cell membranes. This research contributes to a deeper understanding of the role of CO2 nanobubbles in drug absorption and subsequent release into the bloodstream. The findings suggest that utilizing CO2 nanobubbles could enhance T4 bioavailability and cell permeability, leading to more efficient transport into cells. Additional research opens the possibility of employing lower concentrations of this class of drugs, thereby potentially reducing the associated side effects due to poor absorption.

FeetMe® Monitor-connected insoles are a valid and reliable alternative for the evaluation of gait speed after stroke.

BACKGROUND: One of the main challenges after stroke is gait recovery. To provide patients with an individualized rehabilitation program, it is helpful to have real-life objective evaluations at baseline and at regular follow-ups to adjust the program and verify potential improvements. OBJECTIVES: To evaluate the accuracy and reliability of a fully stand-alone system of connected insoles (FeetMe® Monitor) against a widely used clinical walkway system (GAITRite®). METHODS: Twenty-nine subjects with a stroke that occurred >6 months prior participated in the study. Their comfortable gait over three 8-m trials was evaluated by four raters, on Day 1 and Day 7, using simultaneously FeetMe® Monitor and GAITRite®. Velocity, stride length, cadence, stance, and swing duration were calculated on both sides over three sequences of gait: one single stride, 8 m, and three 8-m trials pooled. The Intra-class Correlation Coefficient (ICC) and the Bland-Altman plot evaluated the construct validity (inter-device) and the reliability (test-retest and inter-rater) of FeetMe® Monitor. RESULTS: Through all gait analysis sequences, the inter-device ICCs were >0.95 for velocity, stride length, and cadence. Ranges of inter-device ICCs were [0.77-0.94] for stance duration for both limbs, and for swing duration [0.32-0.57] on the non-paretic side and [0.75-0.90] on the paretic side. Test-retest and inter-rater ICCs for all parameters were >0.73 for one single stride, >0.88 for 8-m trials and >0.94 for three 8-m trials. CONCLUSION: FeetMe® Monitor is an accurate and reliable system for measurement of gait velocity, stride length, cadence, and stance duration in chronic hemiparesis.

Modafinil as an adjunctive treatment to sleep deprivation in depression.

Sleep deprivation (SD) is a rapid-acting treatment for depression, but its clinical efficacy is hampered by high relapse rates after recovery sleep, and its effectiveness is reduced by the demanding effort needed for the patient to stay awake. To our knowledge, this is the first reported case of a successful treatment of depression with the combination of SD and the wakefulness-promoting agent modafinil. We suggest that modafinil may reinforce the action of SD, possibly by preventing daytime naps and microsleep, and may sustain the antidepressant effect of SD, possibly by stabilizing the resynchronization between the circadian clock and the sleep-wake cycle.