Cost-effectiveness analysis of rimegepant for on-demand acute treatment of migraine in China.

Purpose: This study assesses the cost-effectiveness of rimegepant for the on-demand acute treatment of migraine in the Chinese population, focusing on headache relief within a 2 h timeframe. Utilizing data from Phase III clinical trials on rimegepant involving Asian populations, this analysis aims to provide essential insights for healthcare decision-making in the context of migraine management in China. Patients and methods: Employing a decision tree model, this research evaluates the cost-effectiveness of rimegepant over a concise 2 h period, exclusively considering its direct market price of 219.00 CNY per dose for on-demand, single-use treatment upon approval in China. This model is based on pain relief outcomes from a clinical trial, categorizing health outcomes by the achievement of pain freedom and alleviation from the most bothersome symptom within two hours post-administration. Results: The study unveils that rimegepant adds 0.0018 quality-adjusted life days (QALD) with an incremental cost-effectiveness ratio (ICER) of 122,166.07 CNY/QALD. Against a daily cost-effectiveness threshold derived from the 2023 per capita GDP of China (734.45 CNY/day), rimegepant falls short of proving its cost-effectiveness. A significant price reduction to approximately 1.32 CNY per dose is required for rimegepant to be considered cost-effective within this framework. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of these results. Conclusion: While rimegepant shows clinical efficacy in providing rapid relief from migraine symptoms, its current pricing exceeds the threshold for cost-effectiveness in the Chinese healthcare setting. This study underscores the need for price adjustments to enhance the accessibility and economic viability of new migraine treatments.

Ca2+ enhanced far-red emission performance and efficiency of SrGd2Al2O7:Mn4+ phosphor for the potential application in plant growth lighting.

Mn-based phosphors with the wavelength of 700-750 nm are an important category of far-red phosphors that have promising potential in the application of plant lighting, and the higher ability of the far-red light emitting of the phosphors is beneficial to plant growth. Herein, a series of Mn4+- and Mn4+/Ca2+-doped double perovskite SrGd2Al2O7 red-emitting phosphors with wavelengths centered at about 709 nm were successfully synthesized by means of a traditional high-temperature solid-state method. First-principles calculations were conducted to explore the intrinsic electronic structure of SrGd2Al2O7 for a better understanding of the luminescence behavior in this material. Extensive analysis demonstrates that the introduction of Ca2+ ions into the SrGd2Al2O7:Mn4+ phosphor has significantly boosted the emission intensity, internal quantum efficiency, and thermal stability by 170%, 173.4%, and 113.7%, respectively, which are superior to those of most other Mn4+-based far-red phosphors. The mechanism of the concentration quench effect and the positive effect of co-doping Ca2+ ions in the phosphor were extensively explored. All studies suggest that the SrGd2Al2O7:0.1%Mn4+, 11%Ca2+ phosphor is a novel phosphor that can be used to effectively promote the growth of plants and regulate the flowering cycle. Therefore, promising applications can be anticipated from this new phosphor.

tDCS Anodal Stimulation of the Right Dorsolateral Prefrontal Cortex Improves Creative Performance in Real-World Problem Solving.

Brain regions associated with creativity is a focal point in research related to the field of cognitive neuroscience. Previous studies have paid more attention to the role of activation of the left dorsolateral prefrontal cortex in creativity tasks, which are mostly abstract conceptual tasks, and less attention to real-world creativity tasks. The right dorsolateral prefrontal cortex is involved in functions such as visuospatial processing, which may have a positive impact on innovative solutions to real-world problems. In this study, tDCS technology was used to explore the effect of anodal stimulation of the right dorsolateral prefrontal cortex on design creativity performance in a real-word problem-solving task related to product design. The experimental task comprised three stages, of which the first two were idea generation stages based on divergent thinking using text and graphics, respectively, whereas the third was the creative evaluation stage based on convergent thinking. Thirty-six design students were recruited to partake in the experiment. They were randomly assigned into anodal stimulation and sham stimulation groups. The results showed that anodal stimulation of the right dorsolateral prefrontal cortex produced a significant positive effect during the creative evaluation stage, promoting the usefulness of ideas (p = 0.009); thus, improving product creativity scores. However, there was no significant impact on the idea generation stage (p > 0.05), which is dominated by divergent thinking. The results suggest that activating the right dorsolateral prefrontal cortex with tDCS can improve people's performance in creative activities by promoting convergent thinking rather than divergent thinking. It also provides further evidence that the right hemisphere of the brain has an advantage in solving complex problems that require the participation of visuospatial information.

Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress.

This study was designed to investigate the expression of short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid ß-oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time-dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hypertensive rats (SHR). On the other hand, swim-trained rats developed physiological cardiac hypertrophy, whereas SHR developed pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited divergent SCAD changes in myocardial fatty acids utilization. In addition, the expression of SCAD was significantly decreased in pathological cardiomyocyte hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which showed that the down-regulation of SCAD expression may play an important role in pathological cardiac hypertrophy. The changes in peroxisome proliferator-activated receptor α (PPARα) was accordant with that of SCAD. Moreover, the specific PPARα ligand fenofibrate treatment increased the expression of SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that the down-regulated expression of SCAD in pathological cardiac hypertrophy may be responsible for 'the recapitulation of foetal energy metabolism'. The deactivation of PPARα may result in the decrease in SCAD expression in pathological cardiac hypertrophy. Changes in SCAD are different in pathological and physiological cardiac hypertrophy, which may be used as the molecular markers of pathological and physiological cardiac hypertrophy.

Effects of ERK1/2/PPARα/SCAD signal pathways on cardiomyocyte hypertrophy induced by insulin-like growth factor 1 and phenylephrine.

AIMS: Short-chain acyl-CoA dehydrogenase (SCAD) is a key enzyme in fatty acid oxidation. In the present study we aim to investigate the changes in SCAD between pathological and physiological cardiomyocyte hypertrophy. We also explore the different signaling pathways of pathological and physiological cardiomyocyte hypertrophy. MAIN METHODS: After neonatal rat cardiomyocytes were treated as setups, cell surface area, expression of SCAD, PPARα, phospho-ERK1/2, activity of SCAD, free fatty acid content and ATP content in the cardiomyocytes were measured. KEY FINDINGS: Neonatal rat cardiomyocytes treated by PE showed an increased cell surface area and free fatty acid content, increased ERK1/2 phosphorylation, decreased expression of PPARα, decreased expression and activity of SCAD and decreased levels of ATP. Neonatal rat cardiomyocytes treated by IGF-1 showed the reverse effects except for the cell surface area. PPARα inhibitor GW6471 and PPARα activator Fenofibrate treatments abrogated the effects induced by IGF-1 and PE in cardiomyocytes respectively, as well as ERK1/2 activator EGF and ERK1/2 inhibitor PD98059. SIGNIFICANCE: SCAD has different changes between pathological and physiological cardiomyocyte hypertrophy. The ERK1/2/PPARα/SCAD signaling pathways play different roles in pathological and physiological cardiomyocyte hypertrophy. SCAD may be used as a new target to prevent the development of pathological cardiac hypertrophy.

Upregulation of Nox4 promotes angiotensin II-induced epidermal growth factor receptor activation and subsequent cardiac hypertrophy by increasing ADAM17 expression.

BACKGROUND: Activation of epidermal growth factor receptor (EGFR) plays an important role in angiotensin II (Ang II)-induced cardiac hypertrophy, but little is known about the underlying mechanism that results in EGFR activation. In this study, we aimed to confirm the important role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) in Ang II-induced EGFR activation and subsequent cardiac hypertrophy by upregulating expression of a disintegrin and metalloproteinase (MMP)-17 (ADAM17). METHODS: Small interference RNA (siRNA) was adopted to knock down ADAM17 or Nox4 expression. Nox4 plasmid was used to construct cardiomyocytes with Nox4 overexpression. RESULTS: Nox4 and ADAM17 increased in an abdominal artery coarctation-induced model of myocardial hypertrophy. In vitro studies showed that Nox4 was required in Ang II-induced EGFR activation and subsequent myocardial hypertrophy. Nox4 siRNA and Nox4 overexpression demonstrated that Nox4 controlled the transcription and translation of ADAM17. Furthermore, we observed that the ratio of phosphor-EGFR (p-EGFR) to EGFR was significantly reduced by ADAM17 siRNA in hypertrophic cardiomyocytes. Enzyme-linked immunosorbent assay studies revealed that Nox4 and ADAM17 mediated the release of mature heparin-binding EGF-like growth factor (HB-EGF), which played a critical role in the Ang II-induced EGFR activation. Moreover, the results of reactive oxygen species (ROS) scavenging by N-acetyl cysteine (NAC) indicated that ROS were required in the Nox4-mediated upregulation of ADAM17 expression. CONCLUSIONS: In summary, Nox4 is required in Ang II-induced EGFR activation and subsequent cardiac hypertrophy; it increased the expression of ADAM17, which induced the release of mature HB-EGF. ROS were also required in the Nox4-mediated upregulation of ADAM17 expression.

Fenofibrate ameliorates cardiac hypertrophy by activation of peroxisome proliferator-activated receptor-α partly via preventing p65-NFκB binding to NFATc4.

Fenofibrate, a specific peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, was reported to inhibit cardiac hypertrophy. However, the detailed molecular mechanisms and particularly the transcriptional components that are decisive in this process remain to be elucidated. Here we found that fenofibrate ameliorated cardiac hypertrophy in vitro and in vivo. Fenofibrate prevented nuclear translocation of nuclear factor of activated T-cells c4 (NFATc4) and p65 subunit of nuclear factor-kappa B (p65-NFκB) induced by pressure overload or angiotensinII (AngII). Moreover, fenofibrate increased the association of PPAR-α with NFATc4 in nucleus, which inhibited the interaction of NFATc4 with p65-NFκB. Our results suggested that the anti-hypertrophic effect of fenofibrate may be partially attributed to activation of PPAR-α, which decreases the binding of p65-NFκB to NFATc4 and thereby inhibits transactivation of NFATc4.