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Background: Clinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB.Methods: One hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured.Results: Compared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB.Conclusions: This study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS. [ABSTRACT FROM AUTHOR]

Quinoa is widely recognized for its exceptional nutritional properties, particularly its complete protein content. This study, for the first time, investigates the effects of processing methods (boiling and extrusion) and farming conditions (conventional and organic) on the proteomic profile. Following a label-free shotgun proteomics approach, a total of 1796 proteins were identified and quantified across all quinoa samples. Regarding processing, both boiling and extrusion produced protein extracts with lower total protein content, with the number of identified proteins decreasing from 1695 in raw quinoa to 957 in processed quinoa. Boiling led to a reduction in protein diversity and expression, while extrusion, which involves high temperatures and pressures, specifically decreased the abundance of high molecular mass proteins. Concerning cultivation practices, organic farming was associated with a broader protein diversity, especially proteins related to translation (28 vs 5%), while conventional farming showed a higher abundance of catalytic and enzymatic proteins (67 vs 46%). These findings highlight the distinct proteomic changes induced by different processing methods and farming conditions, offering valuable insights to manage quinoa's nutritional, bioactive, and functional properties across various production practices.

This study presents the development of an analytical characterization strategy tailored to end products derived from an alfalfa ( Medicago sativa )-based biorefinery with particular emphasis on protein concentrates and phenolic-enriched fractions. Our approach began with a comprehensive full-factorial experimental design aimed at optimizing the extraction process, taking care to design a biocompatible extraction protocol. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) techniques were used to characterize the molecular profile of the extracts. In particular, the extracts showed a significant relative abundance of flavonoids and isoflavonoids in both their aglycone and glycosylated forms, in which antioxidant activity was evaluated. In addition, we elucidated the proteomic profiles of the protein concentrates. This proteomic characterization served as a valuable resource for understanding the differences between these end products, providing insights that can guide informed decisions about their potential applications.

Alzheimer's disease (AD) poses a global health challenge, demanding innovative approaches for effective treatments. Clerodendrum infortunatum Linn. (Lamiaceae) is a shrub traditionally used as a medicinal plant to treat inflammation, skin diseases, and bronchitis. This study aims to identify the main bioactive metabolites in C. infortunatum using LC-QTOF-MS/MS and investigate its potential in protecting against cognitive decline in rats with scopolamine-induced AD disease. Metabolite profiling was performed on the methanol extract of the plant's aerial parts using LC-QTOF-MS/MS. The inhibitory activity of the acetylcholinesterase enzyme was measured in vitro. To evaluate the cognitive effects, the methanol extract was orally administered at three doses (100, 200, and 400 mg/kg) to scopolamine-induced AD rats, and their cognitive functions were assessed using the novel object recognition test. Additionally, acetylcholinesterase enzyme activity, as well as the levels of acetylcholine, dopamine, noradrenaline, glutathione, malondialdehyde, tumor necrosis factor-α, interleukin-1β, and amyloid-β in the rat hippocampus, were measured using ELISA, followed by histopathological evaluation. A total of 79 metabolites, spanning various chemical classes, such as organic acids, phenolic acids, phenylpropanoids and phenylethanoids, flavonoids, coumarins, other phenolics, and fatty acids and their derivatives, were identified. The results showed that the extract promoted enhanced cognitive functions in the novel object recognition test. Scopolamine administration significantly altered the acetylcholinesterase enzyme activity and biomarker levels in the rat's hippocampus. However, treatment with C. infortunatum at 200 and 400 mg/kg almost restored these neurotransmitter levels to normal, which was further confirmed by histopathological analysis. This study demonstrates the therapeutic potential of C. infortunatum in mitigating cognitive decline in AD, with its first metabolite profiling revealing a range of bioactive compounds. The extract improved cognitive function in scopolamine-induced AD rats, restored acetylcholinesterase activity, normalized neurotransmitter levels, and reduced oxidative stress and inflammation. These findings suggest that C. infortunatum is a promising candidate for the development of natural therapies targeting AD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The experiments adhered to the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (NIH Publication No 85–23, 2011). Approval was granted by the Research Ethics Committee of the Faculty of Pharmacy of Cairo University (approval code: MP (3118)). ARRIVE guidelines: The study is reported in accordance with ARRIVE guidelines. A statement naming the person who identified the plant: The aerial parts of C. infortunatum were authenticated by Agriculture Engineer Therese Labib, a plant taxonomy consultant of the Ministry of Agriculture (Giza, Egypt). Voucher specimen statement: The plant material was collected with permission in compliance with national guidelines from the Agriculture Research Center, Giza, Egypt at “9 Cairo University Road, Giza District, Giza Governorate”. Samples of the plant material were deposited at the herbarium of the Faculty of Pharmacy, Cairo University, Cairo, Egypt (sample No.10.3.2021)., (© 2024. The Author(s).)

Snake melon (Cucumis melo var. flexuosus, CM) is a gourd with health-promoting nutritional traits and unexplored phytochemicals. This study aims to comprehensively investigate the phytoconstituents in the fruits, leaves, roots, seeds, and stems of CM, using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Consequently, 118 metabolites were identified, encompassing phenolic compounds, flavonoids, megastigmanes, lignans, cucurbitacins, and fatty acids. Multivariate data analysis revealed differences in the metabolite composition of CM organs and correlated these variations with the potential in-vitro anti-inflammatory properties assessed against RAW 264.7 macrophages through the down-regulation of cyclo-oxygenase-Ⅱ, nuclear factor-kappa B, and tumor necrosis factor-α. The results indicated that leaf and seed extracts showed the highest anti-inflammatory activity due to their enrichment in several flavonoids, phenolic glycosides, and a megastigmane. These findings emphasize the health benefits of CM organs as potential functional foods and functional food by-products, serving as a natural source for developing new anti-inflammatory agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Many plants are reported to enhance cognition in amnesic-animal models. The metabolite profile of Cordia dichotoma fruit methanolic extract (CDFME) was characterized by LC-QTOF-MS/MS, and its total phenolics content (TPC) and total flavonoids content (TFC) were determined. In parallel, its cognitive-enhancing effect on scopolamine (SCOP)-induced AD in rats was evaluated. The TPC and TFC were 44.75 ± 1.84 mg gallic acid equiv. g -1 sample and 5.66 ± 0.67 mg rutin equiv. g -1 sample, respectively. In total, 81 metabolites were identified, including phenolic acids, lignans, coumarins, amino acids, fatty acids, and their derivatives, fatty acid amides, polar lipids, terpenoids, and others. The most abundant metabolites identified were quinic acid, caffeoyl-4'-hydroxyphenyllactate, rosmarinic acid, and oleamide. CDFME (200 mg kg -1 ) was found to significantly enhance recognition memory in the novel object recognition test. Furthermore, it nearly corrected acetylcholinesterase (AChE), acetylcholine, noradrenaline, and dopamine hippocampal levels, which changed due to SCOP. Further in silico validation of the in vivo results was conducted, focusing on the most abundant metabolites. Molecular docking showed that rosmarinic acid, caffeoyl-4'-hydroxyphenyllactate, sebestenoid C, and sagerinic acid exhibited the greatest affinity for receptor binding against AChE. However, molecular dynamics and mechanics calculations clarified that the complex of caffeoyl-4'-hydroxyphenyllactate with AChE was the most stable one. This study represents the first comprehensive metabolite profiling of CDFME to assess its cognition-enhancing effect both in vivo and in silico . These results demonstrate that CDFME protects against SCOP-induced cognitive impairment. Thus, additional preclinical and clinical studies on CDFME may provide an attractive approach in pharmacotherapy and AD prophylaxis., Competing Interests: Authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Objectives: Proton pump inhibitors (PPIs) are used to manage excess stomach acid production and provide gastroprotection from bleeding risk-increasing drugs (BRIDs). We aimed to determine the prevalence of potentially inappropriate PPI use in nursing homes and associated factors., Design: Longitudinal cohort study using 8 years of electronic data., Setting and Participants: The study included 6439 permanent residents aged ≥65 years from 34 homes managed by 2 aged care providers in New South Wales., Method: Continuous PPI use (>12 weeks) in the absence of long-term BRID (>30 days) use was deemed inappropriate overuse whereas long-term BRID use without concomitant PPI for gastroprotection was classified as inappropriate underuse. Binary logistic regression was used to determine factors associated with PPI overuse., Results: Fifty-four percent of residents (n = 3478) received a PPI, with a median duration of 46 weeks, whereas 58.5% (n = 3770) were long-term BRID users. Four of 5 PPI users (83.6%, n = 2906) used PPIs for >12 weeks, and after accounting for BRID use, the prevalence of inappropriate PPI overuse was 27.1% (n = 944). PPI overuse was 4 times more likely in residents in provider A compared with residents in provider B [odds ratio (OR) 4.08, 95% CI 2.73-6.09]. The prevalence of PPI underuse was 38.5% (n = 1452)., Conclusions and Implications: One in 4 PPI users exceeded the clinically recommended duration, whereas 2 in 5 long-term BRID users did not receive a PPI for gastroprotection. There is a pressing need for tailored interventions, such as medication reviews and deprescribing initiatives, to improve PPI prescribing., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction Mental health conditions, such as depression, anxiety, and psychological distress in the adult population significantly increased during the COVID-19 pandemic. However, the rates of prescribing psychotropic medications in adults during the COVID-19 period have not been well explored. Aim The aim of this study was to examine the association between demographic characteristics and rates of prescribing psychotropic medications to general practice patients during 2018-2022. Methods A total of 154 528 general practice patients aged 20 years and above were included in the study. A mixed effects negative binomial regression model was employed and incidence risk ratios (IRRs) with corresponding 95% confidence interval (CI) are presented to measure the association of demographic characteristics with rates of prescribing psychotropic medication. Results Over half (56.2%) of study subjects were female and 41.4% were aged between 20 and 39 years. Males had lower prescribing rates of antidepressants (IRR = 0.95; 95% CI: 0.94, 0.97) and hypnotics and sedatives (IRR = 0.97; 95% CI: 0.96, 0.99) than females. People in the age group 60+ years (compared with age group 20-39 years) and those in low and middle socio-economic status (SES) categories (compared with high SES) had higher rates of prescribing psychotropic medication. Conclusion Females, people aged 60+ years, and people with low and middle SES had higher prescribing rates of psychotropic medication. A consistent increase in prescribing rates over time, particularly during the COVID-19 pandemic, was observed. It is important that health care planners and policy makers monitor and account for population diversity and equity.

This review provides an in-depth exploration of capillary electrophoresis-mass spectrometry (CE-MS) in biomolecular research from 2020 to 2024. CE-MS emerges as a versatile and powerful tool due to its numerous advantages, facilitating the analysis of various biomolecules, including proteins, peptides, oligonucleotides, and other metabolites, such as lipids, carbohydrates, or amines, among others. The review extends to various CE modes and interfaces for the CE-MS coupling, offering comprehensive insights into their applications within biomolecular research. Furthermore, it effectively summarizes the conditions employed in CE-MS while also addressing critical aspects such as sample preparation requirements. Despite its advantages, the review highlights a gap between discovery and practical implementation, underscoring the need for large-scale validation and method standardization to fully realize the potential of CE-MS in biomolecular research., (© 2024 The Author(s). Electrophoresis published by Wiley‐VCH GmbH.)

BACKGROUND PISUM SATIVUM: (PS) is a universal legume plant utilized for both human and animal consumption, particularly its seeds, known as green peas. The processing of PS in food industries and households produces a significant amount of waste that needs to be valorized., Methods: In this study, the metabolite profiles of the 70% ethanolic extracts of PS wastes, namely peels (PSP) and a combination of leaves and stems (PSLS), were investigated by liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (LC-ESI-QTOF-MS/MS) followed by molecular networking., Results: Different classes of metabolites were identified, being flavonoids and their derivatives, along with phenolic acids, the most abundant categories. Additionally, a comprehensive network pharmacology strategy was applied to elucidate potentially active metabolites, key targets, and the pathways involved in cytotoxic activity against breast cancer. This cytotoxic activity was investigated in MCF-7 and MCF-10a cell lines. Results revealed that PSLS extract exhibited a potent cytotoxic activity with a good selectivity index (IC 50 = 17.67 and selectivity index of 3.51), compared to the reference drug doxorubicin (IC 50 = 2.69 µg/mL and selectivity index of 5.28). Whereas PSP extract appeared to be less potent and selective (IC 50 = 32.92 µg/mL and selectivity index of 1.62). A similar performance was also observed for several polyphenolics isolated from the PSLS extract, including methyl cis p-coumarate, trans p-coumaric acid, and liquiritigenin/ 7-methyl liquiritigenin mixture. Methyl cis p-coumarate showed the most potent cytotoxic activity against MCF-7 cell line and the highest selectivity (IC 50 = 1.18 µg/mL (6.91 µM) and selectivity index of 27.42). The network pharmacology study revealed that the isolated compounds could interact with several breast cancer-associated protein targets including carbonic anhydrases 1, 2, 4, 9, and 12, as well as aldo-keto reductase family 1 member B1, adenosine A3 receptor, protein tyrosine phosphatase non-receptor type 1, and estrogen receptor 2., Conclusion: The uncovered therapeutic potential of PSLS and its metabolite constituents pave the way for an efficient and mindful PS waste valorization, calling for further in-vitro and in-vivo research., (© 2024. The Author(s).)

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems., (© 2024. The Author(s).)

Quinoa is an Andean crop that stands out as a high-quality protein-rich and gluten-free food. However, its increasing popularity exposes quinoa products to the potential risk of adulteration with cheaper cereals. Consequently, there is a need for novel methodologies to accurately characterize the composition of quinoa, which is influenced not only by the variety type but also by the farming and processing conditions. In this study, we present a rapid and straightforward method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to generate global fingerprints of quinoa proteins from white quinoa varieties, which were cultivated under conventional and organic farming and processed through boiling and extrusion. The mass spectra of the different protein extracts were processed using the MALDIquant software (version 1.19.3), detecting 49 proteins (with 31 tentatively identified). Intensity values from these proteins were then considered protein fingerprints for multivariate data analysis. Our results revealed reliable partial least squares-discriminant analysis (PLS-DA) classification models for distinguishing between farming and processing conditions, and the detected proteins that were critical for differentiation. They confirm the effectiveness of tracing the agricultural origins and technological treatments of quinoa grains through protein fingerprinting by MALDI-TOF-MS and chemometrics. This untargeted approach offers promising applications in food control and the food-processing industry., Competing Interests: The authors declare no conflicts of interest.

Introduction: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds., Objectives: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint., Materials and Methods: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes., Results: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC 50 value of 81.64 ± 3.98 μg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site., Conclusion: In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste., (© 2024 John Wiley & Sons Ltd.)

In the present study, an enzymatically hydrolyzed porcine plasma (EHPP) was nutritionally and molecularly characterized. EHPP molecular characterization showed, in contrast to spray-dried plasma (SDP), many peptides with relative molecular masses (Mr) below 8,000, constituting 73% of the protein relative abundance. IIAPPER, a well-known bioactive peptide with anti-inflammatory and antioxidant properties, was identified. In vivo functionality of EHPP was tested in C. elegans and two different mouse models of intestinal inflammation. In C. elegans subjected to lipopolysaccharide exposure, EHPP displayed a substantial anti-inflammatory effect, enhancing survival and motility by 40% and 21.5%, respectively. Similarly, in mice challenged with Staphylococcus aureus enterotoxin B or Escherichia coli O42, EHPP and SDP supplementation (8%) increased body weight and average daily gain while reducing the percentage of regulatory Th lymphocytes. Furthermore, both products mitigated the increase of pro-inflammatory cytokines expression associated with these challenged mouse models. In contrast, some significant differences were observed in markers such as Il-6 and Tnf-α, suggesting that the products may present different action mechanisms. In conclusion, EHPP demonstrated similar beneficial health effects to SDP, potentially attributable to the immunomodulatory and antioxidant activity of its characteristic low Mr bioactive peptides., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Solà-Ginés 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.)

The intricate relationship between smoking and the effects of the antiplatelet drug clopidogrel has been termed the "smoker's paradox". This paradox details the enhanced efficacy of clopidogrel in smokers compared to non-smokers. This review begins with an exploration of the proposed mechanisms of the smoker's paradox, particularly drawing attention to the induction of cytochrome P450 (CYP) isoenzymes via tobacco smoke, specifically the enzymes CYP1A2 and CYP2C19. Moreover, an investigation of the effects of genetic variability on the smoker's paradox was undertaken from both clinical and molecular perspectives, delving into the effects of ethnicity and genetic polymorphisms. The intriguing role of CYP1A2 genotypes and the response to clopidogrel in smoking and non-smoking populations was examined conferring insight into the individuality rather than universality of the smoker's paradox. CYP1A2 induction is hypothesised to elucidate the potency of smoking in exerting a counteracting effect in those taking clopidogrel who possess CYP2C19 loss of function polymorphisms. Furthermore, we assess the comparative efficacies of clopidogrel and other antiplatelet agents, namely prasugrel and ticagrelor. Studies indicated that prasugrel and ticagrelor provided a more consistent effect and further reduced platelet reactivity compared to clopidogrel within both smoking and non-smoking populations. Personalised dosing was another focus of the review considering patient comorbidities, genetic makeup, and smoking status with the objective of improving the antiplatelet response of those taking clopidogrel. In summation, this review provides insight into multiple areas of research concerning clopidogrel and the smoker's paradox taking into account proposed mechanisms, genetics, other antiplatelet agents, and personalised dosing., Competing Interests: Declaration of Competing Interest The authors of the manuscript “Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the Smoker’s Paradox.”, submitted to the journal “Pathology – Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Epilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research explores varying dosages in either adult or paediatric patients, with little or no comparison between the two populations. In this review, we aim at consolidating this data and comparing the effect and pharmacokinetic properties of CBD across these two patient populations. When comparing the absorption, there was insufficient data to show differences between paediatric and adult patients. Similarly, limited information was available in comparing the distribution of CBD, but a higher volume of distribution was found in the paediatric population. From the metabolism perspective, the paediatric population had a greater success rate when treated with the drug compared to the adult population. In the elimination, there were no clear distinctions in the clearance rate between the two populations. The drug's half-life was highly variable in both populations, with paediatrics having a lower range than adults. In summary, the paediatric population had a more significant reduction in the severity of seizures compared to the adult population upon CBD treatment. The complexity in which CBD operates highlights the need for further studies of the compound to further understand why differences occur between these two populations., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)