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IntroductionOpioid use disorder is a cause for concern globally. This study aimed to optimize methadone dose adjustments using mixed modeling and machine learning.MethodsThis retrospective study was conducted at Taichung Veterans General Hospital between January 1, 2019, and December 31, 2020. Overall, 40,530 daily dosing records and 1,508 urine opiate test results were collected from 96 patients with opioid use disorder. A two-stage approach was used to create a model of the optimized methadone dose. In Stage 1, mixed modeling was performed to analyze the association between methadone dose, age, sex, treatment duration, HIV positivity, referral source, urine opiate level, last methadone dose taken, treatment adherence, and likelihood of treatment discontinuation. In Stage 2, machine learning was performed to build a model for optimized methadone dose.ResultsLikelihood of discontinuation was associated with reduced methadone doses (β = 0.002, 95% CI = 0.000–0.081). Correlation analysis between the methadone dose determined by physicians and the optimized methadone dose showed a mean correlation coefficient of 0.995 ± 0.003, indicating that the difference between the methadone dose determined by physicians and that determined by the model was within the allowable range (p

Chelonia mydas (green turtles) are being threatened worldwide by fibropapillomatosis (FP), which has seriously affected their survival. The presence of FP on the body surface and visceral organs of green turtles found dead was confirmed, causing obstruction of the gastrointestinal tract, changes in foraging behavior, and reduction of visceral functions. The etiology of FP has not yet been elucidated, and previous research generally considers that the occurrence of FP is related to the chelonid alphaherpesvirus 5 (ChHV5), associated with low animal immunity, and also with marine environmental factors, such as poor water quality and eutrophication. However, there is no evaluation on the induction of FP pathogenesis associated with the green turtle. In this study, we evaluated blood samples from green turtles with and without FP using de novo transcriptome assembly. Results indicated that 3,090 differentially expressed genes (DEGs) (p < 0.05) were identified, including 1,357 upregulated genes and 1,733 downregulated genes in turtles with or without FP. We observed that DEGs, which are significantly upregulated, are found in cancer development, namely, MAPK1IP1L and APAF1. Furthermore, the infected green turtle indicated that the greater number of DEGs was contributed by the NOD-like receptor signaling pathway, which can be activated through an endocytosis of the viral particle by the immune system cells, and the Wnt signaling pathway, which is believed to have played a role in FP tumorigenesis. We validated the more upregulated/downregulated DEGs in cancer development and immunization, and DEGs such as LEF1, BTRC, and FOSL1 participating in the NOD-like receptor signaling pathway, as well as ERBIN, TRAF6, and NFKB1 in the Wnt signaling pathway, using real-time quantitative polymerase chain reaction (RT-qPCR). Altogether, this study provided some genes as potential markers during FP infection and a further evidence of FP in endangered green turtles in Taiwan.

This study aimed to investigate the risk of vitamin D deficiency in a relatively healthy Asian population, with (i) metabolically healthy normal weight (MHNW) (homeostasis model assessment-insulin resistance [HOMA-IR] < 2. 5 without metabolic syndrome [MS], body mass index [BMI] < 25), (ii) metabolically healthy obesity (MHO) (HOMA-IR < 2.5, without MS, BMI ≥ 25), (iii) metabolically unhealthy normal weight (MUNW) (HOMA-IR ≥ 2.5, or with MS, BMI < 25), and (iv) metabolically unhealthy obesity (MUO) (HOMA-IR ≥ 2.5, or with MS, BMI ≥ 25) stratified by age and sex. This cross-sectional study involved 6,655 participants aged ≥ 18 years who underwent health checkups between 2013 and 2016 at the Chang Gung Memorial Hospital. Cardiometabolic and inflammatory markers including anthropometric variables, glycemic indices, lipid profiles, high-sensitivity C-reactive protein (hs-CRP), and serum 25-hydroxy vitamin D levels, were retrospectively investigated. Compared to the MHNW group, the MHO group showed a higher odds ratio (OR) [1.35, 95% confidence interval (CI) 1.05–1.73] for vitamin D deficiency in men aged < 50 years. By contrast, in men aged > 50 years, the risk of vitamin D deficiency was higher in the MUO group (OR 1.44, 95% CI 1.05–1.97). Among women aged < and ≥ 50 years, the MUO group demonstrated the highest risk for vitamin D deficiency, OR 2.33 vs. 1.54, respectively. Our study revealed that in women of all ages and men aged > 50 years, MUO is associated with vitamin D deficiency and elevated levels of metabolic biomarkers. Among men aged < 50 years, MHO had the highest OR for vitamin D deficiency.

Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome (Scn1aE1099X/+). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in Scn1aE1099X/+ mice. In the hyperthermia-induced seizure experiment, PER clearly increased temperature tolerance and significantly ameliorated seizure frequency and discharge duration. PER also demonstrated antiepileptic effects in a cross-over study and a synergistic effect for attenuating heat-induced seizure when given in combination with stiripentol or valproic acid. The results showed that PER effectively decreased the occurrence of spontaneous recurrent seizures and showed significant therapeutic potential for hyperthermia-induced seizures with regard to both susceptibility and severity in a Dravet syndrome mouse model. Potential therapeutic effects of PER for treatment of Dravet syndrome were demonstrated.

Background and Purpose: Adenosine dysregulation is associated with the occurrence of the epilepsy and equilibrative nucleoside transporters-1 (ENT-1) functions as an important regulator of extracellular adenosine in the brain. This study was aimed to prove the anti-epileptic effect of BBB permeable ENT-1 inhibitors, JMF1907 and J4, on animal models of various epilepsy, and the mechanisms that are involved.Experimental Approach: Maximal electroshock seizure (MES), pentylenetetrazol (PTZ)-induced seizure and kindling models were used as mouse models of generalized tonic-clonic epilepsy, generalized myoclonic epilepsy, and partial epilepsy, respectively. The epilepsy frequency, duration, and Racine score were evaluated. Whole-cell recordings were made from the hippocampal dentate granule cells by using a patch-clamp technique in the brain slice of the mice.Key Results: In MES, JMF1907 at a dose of 5 mg kg–1 was efficacious in decreasing hindlimb extension, while J4 did not decrease hindlimb extension until a higher dose (10 mg kg–1). Both JMF1907 and J4 were more potent in lengthening onset latency than ethosuximide (ETH) in PTZ-induced myoclonic epilepsy model, whereas ETH had better effects on the Racine score. In kindling model, JMF1907 and J4 at a dose of 1 mg kg–1 had effects on seizure frequency and duration, and the effects of JMF1907 were comparable with those of carbamazepine. Both JMF1907 and J4 can reduce the glutamatergic spontaneous excitatory post-synaptic currents (sEPSCs) frequency. The maximal inhibition was about 50% for JMF1907 at a concentration of 1 μg L–1, whereas J4 only inhibited 40% of sEPSCs frequency at a dose of 10 μg L–1.Conclusion and Implications: ENT-1 inhibitors, JMF1907 and J4, showed anti-epileptic effects in different epilepsy models and the effects involved pre-synaptic neuronal modulation.

Background: The intrinsic motivation behind the “need to complete” is more influential than external incentives. We introduced a novel progress-bar tool to motivate the completion of programs designed to treat stimulant and cannabis use disorders. We further examined the effectiveness of the progress bar's scoring approach in forecasting consistently negative urine tests.Methods: This study's participants included 568 patients with stimulant, amphetamine-type, and cannabis use disorders who were undergoing 12-month mandatory treatment programs at Taichung Veterans General Hospital in Taiwan. Patients were given scores of 1, -1, or 0 depending on whether they received negative, positive, or missing urinalysis reports, respectively. The autonomic progress bar generated weekly score totals. At the group level, scorei donated scores from all patients for a given week (i denoted the week). Scorei was standardized to adjusted scorei. We then conducted Autoregressive Integrated Moving Average (ARIMA) Model of time-series analyses for the adjusted scorei.Results: A total of 312 patients maintained treatment progress over the 12-month program. The autonomic score calculator totaled the shared achievements of these patients. The coefficients of the lag variables for mean (p), lag variables for residual error term (q), and number of orders for ensuring stationary (d) were estimated at p = 3, d = 4, and q = 7 for the first half of the treatment program, and were estimated at p = 2, d = 2, and q = 3 for the second half. Both models were stationary and tested as fit for prediction (p < 0.05). Sharply raised adjusted scores were predicted during the high-demand treatment phase.Discussion: This study's novel progress-bar tool effectively motivated treatment completion. It was also effective in forecasting continually negative urine tests. The tool's free open-source code makes it easy to implement among many substance-treatment services.