Search

Methadone is a well-tolerated drug that has been used for pain control and the treatment of opioid addiction. However, some fatal cardiac side effects have been reported previously, including ventricular arrhythmia, stress cardiomyopathy, and coronary artery disease. We reported a middle-aged woman receiving high-dose methadone whom was presented with QT prolongation and torsade de pointes. We replaced the methadone with benzodiazepine and gave lidocaine use simultaneously. Thus, QT interval was shortened within the normal limit. Methadone-induced torsade de pointes is a rare but serious event, and QT interval should be monitored periodically to prevent this fatal adverse event, especially some patients with high-dose methadone use.

Alighting aphids probe a new host plant by intracellular test punctures for suitability. These induce immediate calcium signals that emanate from the punctured sites and might be the first step in plant recognition of aphid feeding and the subsequent elicitation of plant defence responses. Calcium is also involved in the transmission of non-persistent plant viruses that are acquired by aphids during test punctures. Therefore, we wanted to determine whether viral infection alters calcium signalling. For this, calcium signals triggered by aphids were imaged on transgenic Arabidopsis plants expressing the cytosolic FRET-based calcium reporter YC3.6-NES and infected with the non-persistent viruses cauliflower mosaic (CaMV) and turnip mosaic (TuMV), or the persistent virus, turnip yellows (TuYV). Aphids were placed on infected leaves and calcium elevations were recorded by time-lapse fluorescence microscopy. Calcium signal velocities were significantly slower in plants infected with CaMV or TuMV and signal areas were smaller in CaMV-infected plants. Transmission tests using CaMV-infected Arabidopsis mutants impaired in pathogen perception or in the generation of calcium signals revealed no differences in transmission efficiency. A transcriptomic meta-analysis indicated significant changes in expression of receptor-like kinases in the BAK1 pathway as well as of calcium channels in CaMV- and TuMV-infected plants. Taken together, infection with CaMV and TuMV, but not with TuYV, impacts aphid-induced calcium signalling. This suggests that viruses can modify plant responses to aphids from the very first vector/host contact.

Calcium (Ca2+) is a second messenger involved in many plant signalling processes. Biotic and abiotic stimuli induce Ca2+ signals within plant cells, which, when decoded, enable these cells to adapt in response to environmental stresses. Multiple examples of Ca2+ signals from plants containing the fluorescent yellow cameleon sensor (YC) have contributed to the definition of the Ca2+ signature in some cell types such as root hairs, pollen tubes and guard cells. YC is, however, of limited use in highly autofluorescent plant tissues, in particular mesophyll cells. Alternatively, the bioluminescent reporter aequorin enables Ca2+ imaging in the whole plant, including mesophyll cells, but this requires specific devices capable of detecting the low amounts of emitted light. Another type of Ca2+ sensor, referred to as GFP-aequorin (G5A), has been engineered as a chimeric protein, which combines the two photoactive proteins from the jellyfish Aequorea victoria, the green fluorescent protein (GFP) and the bioluminescent protein aequorin. The Ca2+-dependent light-emitting property of G5A is based on a bioluminescence resonance energy transfer (BRET) between aequorin and GFP. G5A has been used for over 10 years for enhanced in vivo detection of Ca2+ signals in animal tissues.Here, we apply G5A in Arabidopsis and show that G5A greatly improves the imaging of Ca2+ dynamics in intact plants. We describe a simple method to image Ca2+ signals in autofluorescent leaves of plants with a cooled charge-coupled device (cooled CCD) camera. We present data demonstrating how plants expressing the G5A probe can be powerful tools for imaging of Ca2+ signals. It is shown that Ca2+ signals propagating over long distances can be visualized in intact plant leaves and are visible mainly in the veins.

Primary mediastinal large B-cell lymphoma (PMBCL) is a specific subtype of diffuse large B-cell lymphoma (DLBCL), which occurs more frequently in young women. PMBCL is an uncommon kind of cancer. R-EPOCH is a common therapeutic regimen that is suitable for patients with PMBCL, and could get a relatively high complete remission rate. However, it may not be effective response in patients with relapsed PMBCL. Immunotherapy appears to be helpful in recent years. Therefore, in this case, a 31-year-old female patient with relapsed PMBCL. Progressive disease was identified after rechemotherapy and target therapy, complete remission can be achieved after switching to PD-1 inhibitor plus targeted therapy. These recurrence, progression, remission and follow-up are all displayed well on 18 F-FDG PET/CT. This case with consecutive imaging monitor illustrates that PD-1 inhibitor may be used as a first-line treatment for recurrent PMBCL. In addition, 18 F-FDG PET/CT is strongly recommended for monitoring PMBCL include baseline staging, interim response and follow-up study., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The Construction File (CF) specification establishes a standardized interface for molecular biology operations, laying a foundation for automation and enhanced efficiency in experiment design. It is implemented across three distinct software projects: PyDNA_CF_Simulator, a Python project featuring a ChatGPT plugin for interactive parsing and simulating experiments; ConstructionFileSimulator, a field-tested Java project that showcases 'Experiment' objects expressed as flat files; and C6-Tools, a JavaScript project integrated with Google Sheets via Apps Script, providing a user-friendly interface for authoring and simulation of CF. The CF specification not only standardizes and modularizes molecular biology operations but also promotes collaboration, automation, and reuse, significantly reducing potential errors. The potential integration of CF with artificial intelligence, particularly GPT-4, suggests innovative automation strategies for synthetic biology. While challenges such as token limits, data storage, and biosecurity remain, proposed solutions promise a way forward in harnessing AI for experiment design. This shift from human-driven design to AI-assisted workflows, steered by high-level objectives, charts a potential future path in synthetic biology, envisioning an environment where complexities are managed more effectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ataii et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Intensive plum production usually involves high yields but also high environmental costs due to excessive fertilizer inputs. Quantitative analysis of the environmental effects of plum production is thereby required in the development of optimum strategies to promote sustainable fruit production., Methods: We collected survey questionnaires from 254 plum production farms in Zhao'an county, Fujian province, southeast China to assess the environmental impacts by life cycle assessment (LCA) methodology. The farms were categorized into four groups based on yield and environmental impacts, i.e., LL (low yield and low environmental impact), LH (low yield but high environmental impact), HL (high yield but low environmental impact), and HH (high yield and high environmental impact)., Results: The environmental impacts, i.e., average energy depletion, global warming, acidification, and eutrophication potential in plum production were 18.17 GJ ha -1 , 3.63 t CO 2 eq ha -1 , 42.18 kg SO 2 eq ha -1 , and 25.06 kg PO 4 eq ha -1 , respectively. Only 19.7% of farmers were in the HL group, with 13.3% in the HH group, 39.0% in LL, and 28.0% LH. Plum yields of the HL group were 109-114% higher than the mean value of all 254 farms. Additionally, the HL group had a lower environmental impact per unit area compared to the overall mean value, with a reduction ranging from 31.9% to 36.7%. Furthermore, on a per tonne of plum production basis, the energy depletion, global warming potential, acidification potential, and eutrophication potential of HL farms were lower by 75.4%, 75.0%, 75.6%, and 75.8%, respectively. Overall, the total environmental impact index of LL, LH, HL, and HH groups were 0.26, 0.42, 0.06, and 0.21, respectively., Discussion: Excessive fertilizer N application was the main source of the environmental impacts, the potential to reduce fertilizer N rate can be achieved without compromising plum yield by studying the HH group. The results provide an important foundation for enhancing the management of plum production, in order to promote 'green' agricultural development by reducing environmental impacts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Ye, Tang, Muneer, Christie, Tou, Xu, Shen, Xu and Zhang.)

Background: Few studies have assessed the use of new oral anti-diabetic agents in Asian populations. This study assesses the efficacy and safety of saxagliptin versus placebo in Asian patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Five hundred sixty-eight drug-naïve adult patients with T2DM and glycated haemoglobin levels (HbA(1c)) of 7.0-10.0% (53-86 mmol/mol) were randomized 1 : 1 to receive saxagliptin 5 mg daily or placebo. Efficacy endpoints included changes from baseline to week 24 in HbA(1c) , fasting plasma glucose (FPG), post-prandial glucose area under the curve from 0 to 180 min (PPG AUC(0-180)), and the proportion of patients achieving HbA(1c) <7.0% (53 mmol/mol). Adverse events (AEs) and serious AEs (SAEs) were evaluated., Results: Saxagliptin provided statistically significant adjusted mean decreases from baseline to week 24 compared with placebo, respectively, in HbA(1c) (-0.84% [-9 mmol/mol] versus -0.34% [-4 mmol/mol]; p < 0.0001), FPG (-0.90 versus -0.17 mmol/L; p < 0.0001), and PPG AUC(0-180) (-417 versus -235 mmol · min/L; p = 0.0010). A significantly greater proportion of patients achieved a therapeutic glycaemic response (HbA(1c) <7.0% [53 mmol/mol]) with saxagliptin (45.8%) versus placebo (28.8%; p < 0.0001). The proportions of patients who experienced ≥1 AE (excluding hypoglycaemia) was 43.3% for saxagliptin and 35.6% for placebo. Few patients in either treatment group experienced an SAE (2.8%, saxagliptin; 1.4%, placebo). A low proportion of patients reported hypoglycaemic events (1.8%, saxagliptin; 0.7%, placebo)., Conclusions: Saxagliptin improved glycaemic control and was well tolerated in drug-naïve Asian patients with T2DM., (Copyright © 2011 John Wiley & Sons, Ltd.)

Aim: To assess efficacy and safety of saxagliptin added to metformin versus placebo plus metformin in Asian patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin alone., Methods: Adults (HbA(1c) 7.0-10.0%, on stable metformin ≥ 1500 mg/day) were randomized 1:1 to saxagliptin 5mg daily plus metformin (n = 283) or placebo plus metformin (n = 287). The primary end point was HbA(1c) change from baseline to Week 24., Results: Saxagliptin plus metformin provided significant adjusted mean decreases versus placebo plus metformin (p ≤ 0.0052) in HbA(1c) (-0.78% versus -0.37%), fasting plasma glucose (-1.14 mmol/L versus -0.58 mmol/L), and postprandial glucose area under the curve from 0 to 180 min (-315 mmol min/L versus -160 mmol min/L). Significantly more saxagliptin-treated patients achieved a therapeutic glycemic response (HbA(1c)<7.0%) (46.5% versus 30.5%; p = 0.0001). The proportion of patients experiencing adverse events (excluding hypoglycemia) was similar for saxagliptin plus metformin (42.8%) versus placebo plus metformin (40.8%). Hypoglycemic events were reported in 1.4% of patients in each group., Conclusion: Saxagliptin added to metformin significantly improved glycemic control and was well tolerated in Asian patients with T2DM who had inadequate glycemic control with metformin and diet and lifestyle modification., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

This randomised, double-blind, parallel-group study assessed the effects of addition of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, tesaglitazar, for 24 weeks to the therapeutic regimen of 392 poorly controlled (glycosylated haemoglobin [HbA1C] 7.5-10%) insulin-treated, type 2 diabetes patients. At 24 weeks, tesaglitazar 0.5 mg resulted in a 0.66% (95% confidence intervals: -0.85, -0.47; p<0.0001) reduction from baseline in HbA1C, and reduced fasting plasma glucose (p<0.0001) and daily insulin dose (p=0.014) versus placebo. After 24 weeks, tesaglitazar caused greater improvements from baseline in triglycerides (p<0.0001), high-density lipoprotein cholesterol (HDL-C) (p<0.001), non-HDL-C (p<0.05), apolipoprotein (apo)A-I (p<0.05) and apoB levels (p<0.01) than placebo. Tesaglitazar was generally well tolerated but was associated with a greater increase in serum creatinine level than placebo. The clinical development of tesaglitazar is no longer continuing; its effects on the glucose and lipid abnormalities of type 2 diabetes suggest that the concept of dual PPARalpha/gamma agonism is worthy of further investigation.

Objective: The Glucose and Lipid Assessment in Diabetes (GLAD) trial examined the dose-response relationship of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist tesaglitazar in type 2 diabetic patients., Study Design: GLAD was a 12-week, multicenter, international, randomized, parallel-group trial. Five-hundred men and women aged 30-80 years with type 2 diabetes (fasting plasma glucose [FPG] > or = 126 mg/dL [> or = 7.0 mmol/L]) received once-daily, double-blind placebo or tesaglitazar (0.1 mg, 0.5 mg, 1.0 mg, 2.0 mg, or 3.0 mg) or open-label pioglitazone (45 mg), included as a therapeutic benchmark., Main Outcome Measures: Placebo-corrected changes from baseline in FPG (primary end point), plasma lipids, and insulin-resistance measures., Results: At baseline, the mean patient age was 56.1 years, 57.5 years, and 58.9 years for placebo, across tesaglitazar groups, and for pioglitazone, respectively. For the corresponding groups, mean body mass index was 30.6 kg/m2, 30.9 kg/m2, and 29.7 kg/m2, and mean HbA1c was 7.0%, 7.2%, and 7.0%, respectively. At 12 weeks, tesaglitazar 0.5 mg, 1.0 mg, 2.0 mg, and 3.0 mg produced statistically significant reductions in FPG (-30.3 mg/dL, -41.1 mg/dL, -55.0 mg/dL, -60.9 mg/dL; p < 0.0001), triglycerides (-17.2%, -32.9%, -41.0%, -40.9%; p < 0.01), and apolipoprotein B (-15.0%, -15.7%, -21.0%, -22.3%, respectively; p < 0.0001). Tesaglitazar at doses > or = 1.0 mg significantly increased high-density lipoprotein-cholesterol (HDL-C) (15.0%, 13.0%, 12.9%; p < 0.001), and reduced non-HDL-C (-13.2%, -22.2%, -25.0%; p < 0.0001), very-low-density lipoprotein-cholesterol (VLDL-C) (-36.9%, -49.8%, -52.5%; p < 0.0001), and total cholesterol (-6.8%, -14.1%, -15.5%, respectively; p < 0.01). Tesaglitazar > or = 0.5 mg improved insulin-resistance measures. Although no formal statistical analyses were performed between active treatments, improvements in efficacy measures with tesaglitazar 1.0 mg were numerically similar to or greater than those with pioglitazone. Similar numbers of adverse events occurred in the tesaglitazar < or = 1.0 mg, placebo, and pioglitazone arms, but there was an increasing frequency of discontinuations due to pre-specified hematologic and clinical-chemistry criteria with tesaglitazar doses > or = 1.0 mg., Conclusions: In type 2 diabetic patients, tesaglitazar dose-dependently reduced FPG levels at doses > or = 0.5 mg. Other markers of glycemic control, atherogenic dyslipidemia, and measures associated with insulin resistance were improved at doses > or = 0.5 mg or > or = 1.0 mg. Study limitations included that the majority of patients were white, patients had good glycemic control at baseline, and the increased number of early withdrawals in the tesaglitazar 2.0 mg and 3.0 mg doses limits conclusions about the efficacy of these doses. The 0.5 mg and 1.0 mg tesaglitazar doses were identified for further investigation.

Essential hypertension in pediatric patients may require pharmacological treatment. There is a need for efficacious, safe, and well-tolerated antihypertensive agents with a once-a-day dosing regimen in children and adolescents. The aim of the trial was to evaluate the dose-response and tolerability of the dihydropyridine calcium channel blocker, felodipine extended-release tablets (felodipine ER), given once daily to pediatric patients with essential hypertension. A randomized double-blind, parallel-group, multi-center clinical study comparing felodipine ER (2.5, 5, or 10 mg once daily) and placebo was performed on pediatric patients with a baseline systolic (SBP) or diastolic blood pressure (DBP) above the 95th percentile for age, sex, and height. Of 133 randomized patients, 128 (96.2%) completed the 3 weeks of double-blind treatment. The study population included 50% children 6-12 years of age or Tanner stage

Standard therapy in the United States for malignancy-associated hyperuricemia consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes the enzymatic oxidation of uric acid to a 5 times increased urine soluble product, allantoin. Rasburicase is a new recombinant form of urate oxidase available for clinical evaluation. This multicenter randomized trial compared allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at high risk for tumor lysis. Patients received the assigned uric acid-lowering agent for 5 to 7 days during induction chemotherapy. The primary efficacy end point was to compare the area under the serial plasma uric acid concentration curves during the first 96 hours of therapy (AUC(0-96)). Fifty-two patients were randomized at 6 sites. In an intent-to-treat analysis, the mean uric acid AUC(0-96) was 128 +/- 70 mg/dL.hour for the rasburicase group and 329 +/- 129 mg/dL.hour for the allopurinol group (P <.0001). The rasburicase versus allopurinol group experienced a 2.6-fold (95% CI: 2.0-3.4) less exposure to uric acid. Four hours after the first dose, patients randomized to rasburicase compared to allopurinol achieved an 86% versus 12% reduction (P <.0001) of initial plasma uric acid levels. No antirasburicase antibodies were detected at day 14. This randomized study demonstrated more rapid control and lower levels of plasma uric acid in patients at high risk for tumor lysis who received rasburicase compared to allopurinol. For pediatric patients with advanced stage lymphoma or high tumor burden leukemia, rasburicase is a safe and effective alternative to allopurinol during initial chemotherapy.