One of the most promising drugs recently approved for the treatment of various types of cancer is dacomitinib, which belongs to the tyrosine kinase inhibitor class. The US Food and Drugs Administration (FDA) has recently approved dacomitinib as a first-line treatment for patients suffering from non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current study proposes the design of a novel spectrofluorimetric method for determining dacomitinib based on newly synthesized nitrogen-doped carbon quantum dots (N-CQDs) as fluorescent probes. The proposed method is simple and does not require pretreatment or preliminary procedures. Since the studied drug does not have any fluorescent properties, the importance of the current study is magnified. When excited at 325 nm, N-CQDs exhibited native fluorescence at 417 nm, which was quantitatively and selectively quenched by the increasing concentrations of dacomitinib. The developed method involved the simple and green microwave-assisted synthesis of N-CQDs, using orange juice as a carbon source and urea as a nitrogen source. The characterization of the prepared quantum dots was performed using different spectroscopic and microscopic techniques. The synthesized dots had consistently spherical shapes and a narrow size distribution and demonstrated optimal characteristics, including a high stability and a high fluorescence quantum yield (25.3%). When assessing the effectiveness of the proposed method, several optimization factors were considered. The experiments demonstrated highly linear quenching behavior across the concentration range of 1.0−20.0 μg/mL with a correlation coefficient (r) of 0.999. The recovery percentages were found to be in the range of 98.50–100.83% and the corresponding relative standard deviation (%RSD) was 0.984. The proposed method was shown to be highly sensitive with a limit of detection (LOD) as low as 0.11 μg/mL. The type of mechanism by which quenching took place was also investigated by different means and was found to be static with a complementary inner filter effect. For quality purposes, the assessment of the validation criteria adhered to the ICHQ2(R1) recommendations. Finally, the proposed method was applied to a pharmaceutical dosage form of the drug (Vizimpro® Tablets) and the obtained results were satisfactory. Considering the eco-friendly aspect of the suggested methodology, using natural materials to synthesize N-CQDs and water as a diluting solvent added to its greenness profile.
Introduction: This study was performed to determine the levels of α1-acid glycoprotein (AGP) in old-age patients undergoing total hip arthroplasty. AGP is considered an acute phase protein produced during the acute phase reaction in the body to various stimuli; their proper monitoring is thus important.Methods: In order to study how AGP concentrations in old age patients change in response to surgical stress (total hip arthroplasty), a high-performance liquid chromatography assay was performed to measure AGP levels. AGP was isolated from the plasma by adding perchloric acid and was analyzed using PLRP-S 4000°A column. The mobile phase consisted of 1 mL TFA/L of water (Solvent A pH 2) and 1 mL TFA/L of acetonitrile (Solvent B). The gradient used was as follows: 0 min 18% B and 82% A, 15 min 60% B and 40% A, and 17 min 60% B and 40% A followed by column re-equilibration for 7 min before the next injection. AGP peak was obtained between 8.8 and 8.9 min. The method was fully optimised according to established guidelines.Results: The data obtained were analyzed on ChromQuest software. AGP concentrations were determined in all samples, including baseline and samples taken at different timed intervals. The peak for AGP was obtained between 8.8 and 8.9 min for both standard AGP and patient plasma. The graphs indicate that AGP concentration in almost all patient samples increased considerably, especially after 4 h and 24 h—for example, initial concentration in patient 1 was 10.36 mg/100 mL but, after 24 h, increased to 23.50 mg/100 mL. There was thus almost a 13 mg/100 mL increase in 24 h, which is confirmed by AGP concentration increasing after various conditions, including surgery. The increased plasma protein binding was comparatively associated with the unchanged free fraction of the drug.Conclusion: This surgically induced increase in AGP concentration resulted in increased plasma protein binding of the drug (ropivacaine), which in turn kept the free portion of ropivacaine stable during the postoperative period.
Background Diagnostic error is a major source of patient suffering. Researchshows that physicians experience frequent interruptions while being engaged with patients and indicate that diagnostic accuracy may be impaired as a result. Since most studies in the field are observational, there is as yet no evidence suggesting a direct causal link between being interrupted and diagnostic error. Theexperiments reported in this article were intended to assess this hypothesis. Methods Three experiments were conducted to test the hypothesis that interruptions hurt diagnostic reasoning and increase time on task. In the first experiment (N = 42), internal medicine residents, while diagnosing vignettes of actual clinical cases were interrupted halfway with a task unrelated to medicine, solving word-spotting puzzles and anagrams. In the second experiment (N = 78), the interruptions were medically relevant ones. In the third experiment (N = 30), we put additional time pressure on the participants. In all these experiments, a control group diagnosed the cases without interruption. Dependent variables were diagnostic accuracy and amount of time spent on the vignettes. Results In none of the experiments interruptions were demonstrated to influence diagnostic accuracy. In Experiment 1: Mean of interrupted group was 0.88 (SD = 0.37) versus non- interrupted group 0.91 (SD = 0.32). In Experiment 2: Mean of interrupted group was 0.95 (SD = 0.32) versus non-interrupted group 0.94 (SD = 0.38). In Experiment 3: Mean of interrupted group was 0.42 (SD = 0.12) versus non-interrupted group 0.37 (SD = 0.08). Although interrupted residents in all experiments needed more time to complete the diagnostic task, only in Experiment 2, this effect was statistically significant. Conclusions These three experiments, taken together, failed to demonstrate negative effects of interruptions on diagnostic reasoning. Perhaps physicians who are interrupted may still have sufficient cognitive resources available to recover from it most of the time.
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