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Background: Nonsteroidal anti-inflammatory drugs (NSAIDs)-related morbidity and mortality can be reduced through medication counselling and risk reduction. Objectives: This study evaluated the impact of short online modular NSAID training on the type and quality of questions asked, risk factors assessed, and counselling offered by community pharmacists to NSAID users. Methods: A cross-sectional questionnaire-guided survey conducted in Ibadan, Nigeria, among 87 pharmacists evaluated the frequency of counselling, NSAID risk factor assessment and barriers to risk assessment. Additionally, a before-and-after RCT was used to evaluate the impact of short online modular NSAID training for the intervention group (IG) on the type and quality of the questions asked, counselling provided, and risk assessed by the pharmacists. Eight standardised patients, aged 25-43 years, four at pre- and postintervention, presented four standardised scenarios at community pharmacies [IG, n = 22, control group (CG, n = 30)] to assess these outcomes. The quality of each outcome (questions asked, counselling offered and risk assessed) was classified as poor (0-≤20%), fair (>20-≤40%), moderate (>40 - ≤60%), or optimal (>60-100%). The data are presented with descriptive statistics. Results: The community pharmacists reported counselling patients on NSAID precautions (80-86%) and dosages (51-69%). Gastrointestinal bleeding risk was assessed by 61-89% of the pharmacists, and time constraints (39-42%) and patient impatience (47-75%) were some barriers to risk assessment. Online modular educational intervention significantly improved the types and quality of questions asked by pharmacists (CG: poor to fair, 16%-21%; IG: poor to moderate, 14%-45%), NSAID risk factors assessed (CG: poor to poor, 10%-9%; IG: poor to fair, 11%-27%) and counselling offered (CG: poor to poor, 6%-7%; IG: poor to fair, 6%-22%). Conclusions: Short online modular educational training on NSAIDs improved the types and quality of the questions asked, NSAID risk factors assessed, and counselling provided by community pharmacists to patients during consultations.

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Pain has been defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Pets often experience the same pain as people; however, dental pain is often overlooked, discounted, or unseen/hidden in patients, as the inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain. This article discusses types of pain and the methods and medications available to treat and prevent oral pain.

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In the study, the modification of naproxen (NAP) with esters of four amino acids (AAs): glycine (GlyOiPr), L-proline (ProOiPr), L-leucine (LeuOiPr), and L-serine (SerOiPr) isopropyl ester was performed to improve water solubility and enhance the permeation of the drug through the skin in comparison to the parent NAP. The NAP derivatives were prepared using the equimolar ratio of the components. In-depth NMR and FTIR analysis revealed that the salts formed with the proton transfer from the carboxylic group of NAP to the amine group of the appropriate AA ester. The NAP salts exhibited improved solubility in water and PBS solution (pH 7.4) when compared to parent NAP. The values of the partition coefficient (log PO/W) for prepared salts were lower than for NAP, however, the salts maintained hydrophobic character determined by the positive values of log P. The In vitro permeation through the pig skin performed in Franz diffusion cells showed that all NAP salts exhibited a higher cumulative mass of permeated NAP (Q24h) than the parent acid. The highest permeation value was noted for [ProOiPr][NAP], with a pseudo-steady state flux (Jss) 32.5 µg NAP cm-2h-1, and Q24h = 246.4 µg NAP cm-2, it was 2.5 % of the applied dose. Moreover, topical preparations with [ProOiPr][NAP] and NAP were prepared based on two vehicles - Celugel® and Pentravan®- approved in pharmacy recipes. The permeation experiments through the Strat-M® showed, that both the Jss and Q24h of permeated drug from preparations containing [ProOiPr][NAP], were statistically several times greater than from the respective preparations with the unmodified acid. Additionally, preparations with [ProOiPr][NAP] provided significantly improved permeation of NAP than two commercial preparations, one of which contained naproxen as the acid and the other - as the sodium salt.

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AIM: Ankylosing spondylitis (AS) predominantly affects the spine and sacroiliac joints, with rare renal involvement. We investigated the incidence rate and risk factors for chronic kidney disease (CKD) in patients with AS and its relationship with long-term nonsteroidal anti-inflammatory drug (NSAID) use. METHODS: We retrospectively analyzed data of patients diagnosed with AS from the Korean National Health Insurance service. The 3-month, 6-month, and 1-year Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Scores were categorized into four groups, as follows: =0, >0 and ≤33.3, 33.3-66.6, and >66.6. RESULTS: Of the 12 000 patients with AS, 150 were identified with CKD, and the incidence rate was 4.64 per 10 000 patient-years. Factors significantly associated with CKD included age ≥60 years, Charlson Comorbidity Index, hypertension, and diabetes mellitus. In the nested case-control analysis, among the ASAS NSAIDs Intake Scores for 0-365 days from diagnosis, the ≥66.6 group had a significantly lower odds ratio than those of the =0 group. CONCLUSION: The present study established the incidence rate of CKD in Korean patients with AS. Though older age and comorbidities were found to be associated with a higher CKD risk, long-term NSAID use was associated with a lower risk. Therefore, the optimal use of NSAIDs in inflammatory diseases requires extensive research.

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Monitoring of drug use in athletes is of interest both for health and competition-related issues. Considering the advantages of Dried Blood Sampling (low invasiveness, easy sampling, long term storage), we have validated a quantitative LC-MS/HRMS method for the screening of 16 nonsteroidal anti-inflammatory drugs. For all drugs, accuracy and imprecision were within 15% for the 3 levels of quality control and lower than 20% for the lower limit of quantification. Application was performed from samples obtained for Ultra-Trail du Mont-Blanc® 2021 and 2022. A focus on ibuprofen and its metabolites (hydroxyibuprofen, carboxyibuprofen, ibuprofen glucuronide and hydroxyibuprofen glucuronide) was made because the results showed that it was the most detected nonsteroidal anti-inflammatory drug. Further, an interpretation of the ibuprofen concentrations was proposed either from experimental data obtained after an intake of ibuprofen by 10 control subjects, or from a pharmacokinetic modelling and simulations. Depending on the analytical performances of the method, we proposed possible detection windows for ibuprofen in runners. The pharmacokinetic model made it possible to consider two scenarios with and without modification of the total clearance of ibuprofen linked to a modification of the pharmacokinetics of the drugs due to the practice of a long and intense physical activity.

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Pituitary neuroendocrine tumor is the third most common primary intracranial tumor. Its main clinical manifestations include abnormal hormone secretion symptoms, symptoms caused by tumor compression of the surrounding pituitary tissue, pituitary stroke, and other anterior pituitary dysfunction. Its pathogenesis is yet to be fully understood. Surgical treatment is still the main treatment. Despite complete resection, 10%-20% of tumors may recur. While dopamine agonists are effective in over 90% of prolactinomas, prolonged use and individual variations can lead to increased drug resistance and a gradual decline in efficacy, which ultimately requires surgical intervention. Nonsteroidal anti-inflammatory drugs reduce the production of inflammatory mediator prostaglandins by inhibiting the activity of cyclooxygenase and exert antipyretic, analgesic, antiplatelet, and anti-inflammatory effects. In recent years, many in-depth studies have confirmed the potential of nonsteroidal anti-inflammatory drugs as a preventive and antitumor agent. It has been extensively utilized in the prevention and treatment of various types of cancer. However, their specific mechanisms of action still need to be fully elucidated. This article summarizes recent research progress on the expression of cyclooxygenase in pituitary neuroendocrine tumors and the treatment of nonsteroidal anti-inflammatory drugs. It provides a feasible theoretical basis for further research on pituitary neuroendocrine tumors and explores potential therapeutic targets.

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Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most frequent and severe complication following ERCP, elevating both patient suffering and healthcare costs, and posing challenges to the advancement of ERCP techniques. Empirical evidence supports the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of PEP, especially in high-risk populations, as endorsed by both the American Society for Gastrointestinal Endoscopy (ASGE) and the European Society for Gastrointestinal Endoscopy (ESGE). However, the prophylactic efficacy of NSAIDs in average-risk individuals, alongside the ideal drug selection, dosing, and timing of NSAID administration, remains to be elucidated. Furthermore, the synergistic preventive potential of NSAIDs when integrated with other interventions, such as hydration, pancreatic stenting, somatostatin administration, sublingual nitrate application, and epinephrine, warrants further clarification. In this paper, we conduct an exhaustive review of the prophylactic effect and clinical administration of NSAIDs for PEP. We comprehensively synthesize findings from clinical trials investigating NSAIDs, both in monotherapy and combination regimens, for PEP prevention. Additionally, we scrutinize the current landscape of NSAID usage in clinical practice and evaluate their cost-effectiveness. Future research should concentrate on refining NSAID prophylaxis strategies for PEP in patients at different risk levels, while also enhancing adherence to clinical guidelines and alleviating the issue of NSAID cost inflation.

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BACKGROUND: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. METHODS: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. RESULTS: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11-1.44] and 1.12 [CI: 1.00-1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14-56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05-1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. CONCLUSIONS: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic effects on femoroacetabular impingement (FAI) patients undergoing hip arthroscopy surgery (HAS). However, the influence of medication time on the analgesic effect of NSAIDs is uncertain. This study aimed to compare the analgesic effect, joint function, quality of life (QoL), and patients' satisfaction between preoperative and postoperative NSAIDs in these patients. METHODS: In this prospective, observational study, 165 FAI patients undergoing HAS with NSAIDs (celecoxib, meloxicam, and nimesulide) for analgesia were divided into preoperative (PRE-A) and postoperative analgesia (POST-A) groups according to their actual medication. RESULTS: The visual analog scale (VAS) pain scores on the 1st (P < 0.001) and 3rd (D3) (P = 0.015) days after the operation were lower in the PRE-A group versus the POST-A group but not preoperatively (P = 0.262) or on the 7th day after the operation (D7) (P = 0.302). The proportion of patients receiving rescue analgesia decreased in the PRE-A group versus POST-A group (P = 0.041). However, the modified Harris hip score (mHHS), proportion of patients with an mHHS ≥ 70, and EuroQol-5-dimensional score at preoperative, 1st month (M1), and 3rd month (M3) after the operation were similar between the groups (all P > 0.050). The VAS score on D7 was greater in the PRE-A group compared to the POST-A group (P = 0.014), but the scores at M1 and M3 and the satisfaction and very satisfaction rates at D7, M1, and M3 did not differ between the groups (all P > 0.050). Subgroup analysis revealed that the type of NSAID did not affect most outcomes. CONCLUSION: Preoperative NSAIDs elevate analgesic effect and patients' satisfaction, but not joint function or QoL compared to postoperative NSAIDs in FAI patients undergoing HAS.

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Osteoid osteoma is a benign bone tumor that typically presents with nocturnal pain alleviated by nonsteroidal anti-inflammatory medications. The coexistence of osteoid osteoma with sickle cell anemia, a hereditary hemoglobinopathy characterized by vaso-occlusive crises and bone infarcts, poses diagnostic and therapeutic challenges due to overlapping clinical and radiological features. This condition primarily involves the long bones of the lower extremities, particularly the femur and tibia. Despite its benign nature, osteoid osteoma can significantly impact a patient's quality of life due to persistent and intense pain, often leading to substantial sleep disturbances and functional limitations.

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OBJECTIVE: Renal colic (RC) is a common urologic emergency often leading to significant pain and recurrent hospital visits. This study aimed to compare the efficacy and safety of piroxicam versus paracetamol in preventing pain recurrence and hospital readmission in patients treated for RC and discharged from the emergency department (ED). METHODS: A prospective, randomized, single-blind trial was conducted in four EDs. Eligible adults with RC were randomized to receive oral piroxicam, paracetamol, or placebo for 5 days post-ED discharge. Primary outcomes included pain recurrence and ED readmission within 7 days. Secondary outcomes included time to recurrence and treatment-related side effects. RESULTS: Of 1383 enrolled patients, no significant differences were observed among the groups regarding baseline characteristics. Pain recurrence rates within 7 days were 29% (95% confidence interval [CI] 24.9%-33.2%) for piroxicam, 30.3% (95% CI 26.1%-34.5%) for paracetamol, and 30.8% (95% CI 26.6%-35.0%) for placebo, with no significant between-group differences (p = 0.84). Among patients experiencing recurrence, the majority encounter it within the initial 2 days following their discharge (86% in the piroxicam group, 84.1% in the paracetamol group, and 86% in the placebo group, respectively). ED readmission rates were similar across groups: 20.8% (95% CI 17.1%-24.5%) in the piroxicam group, 23.8% (95% CI 19.9%-27.7%) in the paracetamol group, and 22.9% (95% CI 19.1%-26.8%) in the placebo group (p = 0.52). The piroxicam group reported significantly higher adverse effects compared to others. CONCLUSIONS: Piroxicam and paracetamol did not demonstrate efficacy in preventing pain recurrence or ED readmission within the first week following RC treatment.

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CONTEXT: Diabetic eyes suffer from variety of complications including macular edema. Cataract surgery is the most commonly done procedure throughout the world and majority would be diabetics. As pseudophakic-cystoid macular edema (CME) is a known complication following cataract surgery, our study concentrated on finding the role of prophylactic topical nonsteroidal anti-inflammatory drugs (NSAIDs) on change in total macular volume (TMV) postcataract surgery in diabetic eyes. AIMS: To evaluate the role of NSAIDs on change in TMV postcataract surgery in diabetic eyes. SETTINGS AND DESIGN: Retrospective comparative study. SUBJECTS AND METHODS: Data were collected from the medical records department of our institute constituting diabetics undergoing cataract surgery from June-2021 to February-2022. Eighty diabetic eyes were divided into two groups: one group were given topical nepafenac drops and another who were not given. Demographic details, diabetic retinopathy stage, preoperative optical coherence tomography (OCT), and postoperative day (POD) 7, day 28, and 3 months OCT were collected. Statistical analysis was done to compare the change in TMV between both the groups. STATISTICAL ANALYSIS USED: Student's t-test and Chi-squared/Fisher's exact test were employed to find statistically significant differences between the two groups using SPSS-22.0 software. RESULTS: In our study, the mean age in the group with nepafenac was 60.93 ± 5.86 years and 31 (77.5%) had moderate nonproliferative diabetic retinopathy (NPDR), and in the group without nepafenac, the mean age was 58.53 ± 7.41 years and 30 (75%) had moderate NPDR. Majority of the individuals in the study group were known diabetic for 2-5 years. Change in TMV at POD 3 months among two groups was not statistically significant; P = 0.758 (P < 0.05-significant). CONCLUSIONS: Our study concluded that topical-NSAIDs played no role in postoperative period following cataract surgery with respect to change in TMV in diabetic eyes. Thus, prophylactic usage of topical-NSAIDs can be a burden on patient as it has no role in prevention of pseudophakic-CME in those with the duration of diabetes mellitus <5 years and with mild-to-moderate NPDR.

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Background: Osteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs). Aims: To evaluate the efficacy and safety of Osteoking in treating KOA. Methods: In the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc. Results: After 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8-10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs. Conclusion: Osteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4-7 scores. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475.

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The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

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Colorectal cancer is a life-threatening and prevalent type of cancer. However, a number of current treatments have serious side effects, which increase the need for alternatives. Non-steroidal anti-inflammatory drugs have potential chemopreventive capabilities. The present study aimed to confirm this, as well as to investigate potential pathways and reasons for this trait. To accomplish this, cancerous Colo320 and healthy CCD-18 cells were treated with various concentrations of naproxen sodium (NS). A caspase-3 assay revealed a statistically significant increase in caspase-3 activity in Colo320 cells (300%; P<0.01), but not in CCD-18 cells. This chemical was also associated with a significant decrease in Colo320 cell survival (-72.888%; P<0.01), but not CCD-18 cell survival. Furthermore, NS was found to significantly decrease the migration of Colo320 cells (86.58%; P<0.01). Finally, RNA sequencing of cells treated with NS revealed the statistically significant downregulation of the mucin 5B, oligomeric mucus/gel-forming, S100 calcium binding protein A9 and mucin 5AC, oligomeric mucus/gel-forming genes, which are upregulated in colorectal cancer and are known to contribute to cancer proliferation, stemness and drug resistance. These novel biological pathway results were further confirmed using ELISAs. The present study identified a novel molecular mechanism of the anti-colorectal cancer activity of NS.

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BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. METHODS: This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. RESULTS: We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05). CONCLUSION: A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.

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In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.

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The overuse of nonsteroidal anti-inflammatory drugs (NSAIDs) poses many serious environmental and food safety concerns. Development of effective and sensitive sample pretreatment method for monitoring trace NSAIDs from complex samples is of great significance. Depending on the ionic and aromatic structures of NSAIDs, a cationic microporous organic network (MON) named TEPM-BBDC with large specific surface area, good solvent and thermal stabilities, and numerous interaction sites was designed and prepared for efficient solid-phase extraction (SPE) of four typical NSAIDs (flurbiprofen, ketoprofen, naproxen, and diclofenac sodium) from environmental water and milk samples. By anchoring the ionic groups in the conjugated MON frameworks, the prepared TEPM-BBDC offered good extraction for NSAIDs based on the π-π, hydrophobic, ion exchange, and electrostatic interactions. Under the optimal extraction conditions (initial concentration of each NSAID: 200 g L-1; sample volume: 50 mL; desorption solvent: 1.5 mL of MeOH + 1 % NH3·H2O; sample loading rate: 5 mL min-1; NaCl concentration: 0 mmol L-1; pH = 5), the proposed TEPM-BBDC-SPE-HPLC-UV method owned wide linear range (0.50-1000 g L-1), low limits of detection (0.10-0.40 g L-1), large enrichment factors (92.2-99.2), good precisions (intra-day and inter-day, RSD% = 1.3-7.8 %, n = 6) and reproducibility (column-to-column, RSD% = 8.0 %, n = 3). The developed method also exhibited good recoveries (83.6-113.4 %) for the determination of NSAIDs in river water, lake water and milk samples. This work not only revealed the potential of TEPM-BBDC for SPE of ionic NSAIDs in complex samples, but also highlighted the prospect of ionic MONs in sample pretreatment.

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