An expedient and metal-free synthetic route has been developed for the construction of tri- and tetrasubstituted imidazole derivatives via acid promoted multicomponent reaction methodology. The reaction proceeded smoothly with a range of functionalities to produce the imidazole scaffolds in good to excellent yields.
Background The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.Aim To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection.Methods We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109).Results Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010–0.020; p < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727–198.160), the HCV genotype 3–genotype 1 IRR was 4.13 (95% confidence interval: 1.52–11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration.Conclusion Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.
Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors.
Background: A growing population of individuals diagnosed with idiopathic pulmonary fibrosis (IPF) are receiving treatment with nintedanib and pirfenidone. The aim of our study was to assess the incidence of drug-induced liver injury (DILI) associated with the use of pirfenidone and nintedanib in patients with IPF in Taiwan. Methods: We collected a cohort of adult patients diagnosed with IPF between 2017 and 2020. The research outcomes involved assessing the incidence of DILI in patients treated with nintedanib or pirfenidone. Poisson regression analysis was employed to estimate incidence rates, with and without adjustments for covariates, to calculate and present both unadjusted and adjusted incidence rate ratios (IRRs). Results: The risk of DILI was greater in patients who received nintedanib than in those who received pirfenidone during the 1-year follow-up. Patients treated with nintedanib exhibited a heightened risk of DILI based on inpatient diagnoses using specific codes after adjusting for variables such as gender, age group, comorbidities and concomitant medications, with an adjusted incidence rate ratio (aIRR) of 3.62 (95% confidence interval (CI) 1.11–11.78). Similarly, the risk of DILI was elevated in patients treated with nintedanib according to a per-protocol Poisson regression analysis of outcomes identified from inpatient diagnoses using specific codes. This was observed after adjusting for variables including gender, age group, comorbidities, and concomitant medications, with an aIRR of 3.60 (95% CI 1.11–11.72). Conclusion: Data from postmarketing surveillance in Taiwan indicate that patients who received nintedanib have a greater risk of DILI than do those who received pirfenidone.
Aim: The physiological realities between Taekwondo (TKD) simulation kicking training and TKD competition according to the Olympic time frame remain unclear. The purpose of this study is to establish an Olympic match-simulated kicking model and compare its effects with real TKD competition on physiological challenges and hormonal responses during serial matches in elite athletes. Method: Sixteen elite TKD athletes randomly were assigned into either a TKD match-simulated kicking group (TMSK; N = 8, age: 21.3 ± 0.2 years) or a simulated TKD competition group (STC; N = 8, age: 21.6 ± 0.5 years). Both groups performed either simulated kicking or TKD competitions in the same time-course order, and all physiological parameters and blood sampling time-points were identical between groups. The heart rate (HR) and rating of perceived exertion (RPE) were recorded during each match-simulated kicking and TKD competition session. Blood samples were obtained before competition (Pre-Comp.), after competition-in ths case meaning four consecutive matches (End-Comp.), and 24 h after the first match (Next day) for determination of biomarkers of muscle damage (myoglobin and CK), hematological profiles, and hormonal profiles (testosterone and cortisol). Results: The responses of HR, RPE, and blood lactate levels during the consecutive testing sessions showed no differences between TMSK and STC. The changes in CK and myoglobin were greater in STC (p < 0.05), and a greater decrease in red blood cell (RBC) loss was observed in the STC group (p < 0.05). Compared with TMSK, the inflammatory state, reflected by the ratios of neutrophils-to-lymphocyte (NLR) and platelets-to-lymphocyte (PLR), was higher in STC (p < 0.05). Moreover, the catabolic state (cortisol/testosterone) was greater in STC than in TMSK (p < 0.05). Conclusion: We demonstrated that, compared with TMSK, the STC produced greater muscle damage, inflammatory responses, and catabolic stress in the Olympic competition time frame in elite male TKD athletes. Although TMSK is capable of eliciting similar physiological challenges as TKD competition, the muscle damage and hormonal profiles provoked by TMSK were not comparable to TKD competition. Our findings provide science-based data and better understanding for coaches, athletes, and sports scientists to develop TKD-specific training programs for Olympic preparation.
Background: Data on the neuropsychological outcomes after receiving direct-acting antivirals (DAAs) among chronic hepatitis C (CHC) patients have not been well-documented. Aim: This study aimed to evaluate the difference in incidence of neuropsychological disorders (NPDs) after treatment completion between CHC patients receiving interferon (IFN) therapy and DAA therapy. Methods: A nationwide retrospective cohort study was performed using Taiwan's National Health Insurance Research Database (NHIRD) between 2010 and 2018. CHC patients without pre-existing mental disorders were included and divided into the treatment (Tx)-naïve DAA group, retreatment (re-Tx) DAA group, and Tx-naïve IFN group based on their HCV therapy. Propensity score matching was used to balance baseline differences between groups. The primary outcome was the incidence of NPDs during 6 months after completion of therapy. Results: After one-to-one matching, there were 6,461 pairs of patients selected from the Tx-naïve DAA group and Tx-naïve IFN group and 3,792 pairs from the re-Tx DAA group and Tx-naïve IFN group. A lower incidence of NPDs was observed in the Tx-naïve DAA group than in the Tx-naïve IFN group (HR = 0.72, 95% CI = 0.55-0.94, and p = 0.017). The risk of NPDs did not differ between the re-Tx DAA group and the Tx-naïve IFN group (HR = 0.74, 95% CI: 0.52-1.05, and p = 0.092). Conclusion: DAA therapy was associated with lower risk of NPDs when compared with IFN therapy among Tx-naïve CHC patients in a 6-month period after treatment completion, especially among the patients less than 65 years, male gender, and cirrhosis.
Abstract Oxidation of 1‐naphthols to naphthoquinones and subsequent TFA‐catalyzed coupling with electron‐rich benzenes and N‐heterocycles results in regioselective C‐H arylation to produce 2‐substituted 1,4‐naphthoquinones.
Purpose The purpose of the study was to investigate the effect of endurance exercise training with or without protein‐based supplementation on muscle mass and mitochondrial enzyme activity in disuse skeletal muscle atrophy caused by hindlimb suspension (HS). Method Thirty‐two male Sprague‐Dawley (SD) rats (230–280g) were weight‐matched and assigned to the following 4 groups: Free control (FC), Hindlimb Suspension Placebo (H), Hindlimb Suspension + Exercise (HE), Hindlimb Suspension + Exercise+ Nutrition supplementation (HEN). After 10‐days hindlimb suspension (HS) period, all rats were reloaded following one day of rest, thereafter endurance exercise procedure [treadmill running at a speed of 0.6 km/h to 1.2 km/h (+ 0.2 km/h per 3 days), 25 min/day (+ 5 min/3 days), 0% grade] and supplementation (10 ml/kg body wt of solution, containing 300 mg/kg body wt of leucine, 400 mg/kg of HMB, 400 mg/kg of whey protein, 200 mg/kg of casein, 600 mg/kg of glucose) were processed during the two‐weeks reloading period. At the end of intervention, the soleus muscle mass and soleus cross‐section area (CSA) were measured, and the intracellular level oxidative stress status, 4‐Hydroxynonenal protein were measured. Result After two weeks of intervention, body weight, muscle mass and muscle fiber CSA in H, HE, and HEN groups could not be restored, and these parameters were still significantly lower than those of control group ( p < 0.01). HEN group showed the greatest increase in muscle citrate synthase activity in compared with H and HE groups ( p < 0.05). 4‐Hydroxynonenal (4‐HNE) expression was no significantly different among there four groups. Conclusion We demonstrated that two weeks of hindlimb suspension caused muscle atrophy, decreasing body weight, muscle mass, and muscle fiber cross‐section area. However, although endurance exercise training and/or combined with protein supplementation could not full recover unused muscular structure, provision of protein‐based supplementation resulted in an increased muscle mitochondrial enzyme activity.
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