Activation of orexin system facilitates anesthesia emergence and pain control.

Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications.

Serotonin-based nanoparticles represent a class of previously unexplored multifunctional nanoplatforms with potential biomedical applications. Serotonin, under basic conditions, self-assembles into monodisperse nanoparticles via autoxidation of serotonin monomers. To demonstrate potential applications of polyserotonin nanoparticles for cancer therapeutics, we show that these particles are biocompatible, exhibit photothermal effects when exposed to near-infrared radiation, and load the chemotherapeutic drug doxorubicin, releasing it contextually and responsively in specific microenvironments. Quantum mechanical and molecular dynamics simulations were performed to interrogate the interactions between surface-adsorbed drug molecules and polyserotonin nanoparticles. To investigate the potential of polyserotonin nanoparticles for in vivo targeting, we explored their nano-bio interfaces by conducting protein corona experiments. Polyserotonin nanoparticles had reduced surface-protein interactions under biological conditions compared to polydopamine nanoparticles, a similar polymer material widely investigated for related applications. These findings suggest that serotonin-based nanoparticles have advantages as drug-delivery platforms for synergistic chemo- and photothermal therapy associated with limited nonspecific interactions.

To supplement or not to supplement: a cost-utility analysis of calcium and vitamin D repletion in patients after thyroidectomy.

BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy; prevention and treatment remain areas of ongoing debate. The purpose of this study was to determine the incremental cost utility of routine versus selective calcium and vitamin D supplementation after total or completion thyroidectomy. METHODS: A cost-utility analysis using a Markov decision model was performed for a hypothetical cohort of adult patients after thyroidectomy. Routine or selective supplementation of oral calcium carbonate, vitamin D (calcitriol), and intravenous calcium gluconate, when required, was used. Selective supplementation was determined by serum intact parathyroid hormone levels. The incremental cost utility, measured in U.S. dollars per quality-adjusted life-year (QALY), was calculated. RESULTS: In the base-case analysis, the cost of routine supplementation was $102 versus $164 for selective supplementation. Patients in the routine arm gained 0.002 QALYs compared to patients in the selective arm (0.95936 QALYs vs. 0.95725 QALYs). At the population level, this translates into a savings of $29,365/QALY (95% confidence interval, -$66,650 to -$1,772) for routine supplementation. Sensitivity analyses demonstrated that the model was most sensitive to the utility of the hypocalcemic state, postoperative rates of hypocalcemia, and cost of serum parathyroid hormone testing. CONCLUSIONS: Routine oral calcium and calcitriol supplementation in patients after thyroidectomy seems to be less expensive and results in higher patient utility than selective supplementation. Surgeons who have very low rates of hypocalcemia in their patients may benefit less from routine supplementation.