Exploring the Use of Persuasive System Design Principles to Enhance Medication Incident Reporting and Learning Systems: Scoping Reviews and Persuasive Design Assessment.

BACKGROUND: Medication incidents (MIs) causing harm to patients have far-reaching consequences for patients, pharmacists, public health, business practice, and governance policy. Medication Incident Reporting and Learning Systems (MIRLS) have been implemented to mitigate such incidents and promote continuous quality improvement in community pharmacies in Canada. They aim to collect and analyze MIs for the implementation of incident preventive strategies to increase safety in community pharmacy practice. However, this goal remains inhibited owing to the persistent barriers that pharmacies face when using these systems. OBJECTIVE: This study aims to investigate the harms caused by medication incidents and technological barriers to reporting and identify opportunities to incorporate persuasive design strategies in MIRLS to motivate reporting. METHODS: We conducted 2 scoping reviews to provide insights on the relationship between medication errors and patient harm and the information system-based barriers militating against reporting. Seven databases were searched in each scoping review, including PubMed, Public Health Database, ProQuest, Scopus, ACM Library, Global Health, and Google Scholar. Next, we analyzed one of the most widely used MIRLS in Canada using the Persuasive System Design (PSD) taxonomy-a framework for analyzing, designing, and evaluating persuasive systems. This framework applies behavioral theories from social psychology in the design of technology-based systems to motivate behavior change. Independent assessors familiar with MIRLS reported the degree of persuasion built into the system using the 4 categories of PSD strategies: primary task, dialogue, social, and credibility support. RESULTS: Overall, 17 articles were included in the first scoping review, and 1 article was included in the second scoping review. In the first review, significant or serious harm was the most frequent harm (11/17, 65%), followed by death or fatal harm (7/17, 41%). In the second review, the authors found that iterative design could improve the usability of an MIRLS; however, data security and validation of reports remained an issue to be addressed. Regarding the MIRLS that we assessed, participants considered most of the primary task, dialogue, and credibility support strategies in the PSD taxonomy as important and useful; however, they were not comfortable with some of the social strategies such as cooperation. We found that the assessed system supported a number of persuasive strategies from the PSD taxonomy; however, we identified additional strategies such as tunneling, simulation, suggestion, praise, reward, reminder, authority, and verifiability that could further enhance the perceived persuasiveness and value of the system. CONCLUSIONS: MIRLS, equipped with persuasive features, can become powerful motivational tools to promote safer medication practices in community pharmacies. They have the potential to highlight the value of MI reporting and increase the readiness of pharmacists to report incidents. The proposed persuasive design guidelines can help system developers and community pharmacy managers realize more effective MIRLS.

Development of Highly Sensitive Fluorescent Sensors for Separation-Free Detection and Quantitation Systems of Pepsin Enzyme Applying a Structure-Guided Approach.

Two fluorescent molecularly imprinted polymers (MIPs) were developed for pepsin enzyme utilising fluorescein and rhodamine b. The main difference between both dyes is the presence of two (diethylamino) groups in the structure of rhodamine b. Consequently, we wanted to investigate the effect of these functional groups on the selectivity and sensitivity of the resulting MIPs. Therefore, two silica-based MIPs for pepsin enzyme were developed using 3-aminopropyltriethoxysilane as a functional monomer and tetraethyl orthosilicate as a crosslinker to achieve a one-pot synthesis. Results of our study revealed that rhodamine b dyed MIPs (RMIPs) showed stronger binding, indicated by a higher binding capacity value of 256 mg g-1 compared to 217 mg g-1 for fluorescein dyed MIPs (FMIPs). Moreover, RMIPs showed superior sensitivity in the detection and quantitation of pepsin with a linear range from 0.28 to 42.85 µmol L-1 and a limit of detection (LOD) as low as 0.11 µmol L-1. In contrast, FMIPs covered a narrower range from 0.71 to 35.71 µmol L-1, and the LOD value reached 0.34 µmol L-1, which is three times less sensitive than RMIPs. Finally, the developed FMIPs and RMIPs were applied to a separation-free quantification system for pepsin in saliva samples without interference from any cross-reactors.

Cobalt-modulated dual emission carbon dots for ratiometric fluorescent vancomycin detection.

This work presents a simple yet selective fluorometric protocol for the quantification of vancomycin, an important antibiotic for treating infections caused by Gram-positive bacteria. A novel ratiometric fluorometric method for the determination of vancomycin is developed based on dual emissive carbon dots (DECDs) with emission at 382 nm and 570 nm in combination with Co2+ ions. Upon addition of Co2+ions, the fluorescence at 382 nm of DECDs is enhanced while emission at 570 nm remains constant. In the presence of vancomycin, it complexes with Co2+ leading to quenching of the 382 nm fluorescence due to strong binding with Co2+ in the Co@DECDs system. The DECDs are fully characterized by TEM and different spectroscopic techniques. The proposed ratiometric method is based on measuring fluorescence ratio (F570/F382) against vancomycin concentration and the method exhibits a good linearity range from 0.0 to 120.0 ng mL-1 with a low limit of detection (S/N = 3) of 0.31 ng mL-1. The method shows good selectivity with minimal interference from potential interfering species. This ratiometric fluorometric approach provides a promising tool for sensitive and specific vancomycin detection in clinical applications.

Selective fluorescence turn-on detection of combination cisplatin-etoposide chemotherapy based on N-CDs/GSH-CuNCs nanoprobe.

Cisplatin (CIS) and etoposide (ETP) combination therapy is highly effective for treating various cancers. However, the potential for pharmacokinetic interactions between these drugs necessitates selective sensing methods to quantitate both CIS and ETP levels in patient's plasma. This work develops a dual fluorescence probe strategy using glutathione-capped copper nanoclusters (GSH-CuNCs) and nitrogen-doped carbon dots (N-CDs) for the simultaneous analysis of CIS and ETP. The fluorescence signal of GSH-CuNCs at 615 nm increased linearly with CIS concentration while the N-CD emission at 480 nm remained unaffected. Conversely, the N-CD fluorescence was selectively enhanced by ETP with no interference with the CuNC fluorescence. Extensive materials characterization including UV-vis, fluorescence spectroscopy, XRD, and TEM confirmed the synthesis of the nanoprobes. The sensor showed high sensitivity with limits of detection of 6.95 ng mL-1 for CIS and 7.63 ng mL-1 for ETP along with excellent selectivity against potential interferences in rabbit plasma. Method feasibility was demonstrated with application to real rabbit plasma samples. The method was further applied to estimate the pharmacokinetic parameters of CIS before and after ETP coadministration. The dual nanoprobe sensing strategy enables rapid and selective quantitation of CIS and ETP levels to facilitate therapeutic drug monitoring and optimization of combination chemotherapy regimens.

Anti-cancer drug waste disposal practices and wastewater management in hospitals: A Lebanese survey.

INTRODUCTION: To achieve continuous environmental sustainability and protect the population's health, healthcare waste (in liquid or solid form) needs appropriate management and suitable treatment strategies before its final disposal in the environment in order to reduce its adverse impacts. This study aims to identify disparities in the waste management of anti-cancer drugs and the wastewater generated in Lebanese hospitals. METHODS: Three questionnaires were designed to evaluate the level of knowledge, awareness and experience of hospital personnel regardless of their job levels. Data was collected in December 2019 from three departments of each participating hospital: pharmacy, oncology and maintenance departments. A descriptive analysis was conducted to summarise the survey results. RESULTS: The results revealed a lack of transparency and awareness of the participants, with a high frequency of 'prefer not to say' responses when asked about the disposal methods of anti-cancer drugs and with only 5.7% of the participants in the pharmacy department sharing their disposal procedures. The same perception was deduced regarding hospitals' wastewater treatment, where responses were often contradicting, preventing making assumptions about the fate of hospital wastewater. CONCLUSION: The results of this survey support the need to establish a more comprehensive waste management programme in Lebanon that would be maintained through regular training and supervision.

Investigating the impact of the COVID-19 pandemic on the occurrence of medication incidents in Canadian community pharmacies.

As the COVID-19 pandemic unfolded, community pharmacies adapted rapidly to broaden and adjust the services they were providing to patients, while coping with severe pressure on supply chains and constrained social interactions. This study investigates whether these events had an impact on the medication incidents reported by pharmacists. Results indicate that Canadian pharmacies were able to sustain such stress while maintaining comparable safety levels. At the same time, it appears that some risk factors that were either ignored or not meaningful in the past started to be reported, suggesting that community pharmacists are now aware of a larger set of contributing factors that can lead to medication incidents, notably for medication incidents that can lead to harm.

A novel microextraction technique aided by air agitation using a natural hydrophobic deep eutectic solvent for the extraction of fluvastatin and empagliflozin from plasma samples: application to pharmacokinetic and drug-drug interaction study.

This study focuses on the interaction between the antihyperlipidemic drug fluvastatin (FLV) and the antidiabetic drug empagliflozin (EMP), which are commonly co-administered medications. EMP's impact on FLV levels is attributed to its inhibition of organic anion transporting polypeptide 1B1 (OATP1B1), responsible for FLV liver uptake, consequently elevating FLV concentrations in blood. Traditional extraction methods for FLV faced difficulties due to its high hydrophobicity. In this study, a hydrophobic natural deep eutectic solvent (NDES) using air assisted dispersive liquid-liquid microextraction (AA-DLLME) was utilized as an excellent choice for achieving the highest extraction recovery, reaching 96% for FLV and 92% for EMP. The NDES was created through the combination of menthol and hippuric acid in a 4 : 1 ratio, making it a green and cost-effective pathway. Liquid phase microextraction followed by spectrofluorometric measurements of FLV at λem = 395 nm and EMP at λem = 303 nm, with excitation at a single wavelength of 275 nm was carried out. Response surface methodology (RSM) relying on central composite design (CCD) was used to optimize the variables affecting the AA-NDES-DLLME. The optimized conditions for extraction are: NDES volume of 200 µL, centrifugation time of 15 minutes, air-agitation cycle of 6 cycles, and sample pH of 4.0. Under these optimized conditions, the developed method exhibited good linearity and precision. The method showed good recoveries from rabbit plasma samples spiked at varying concentrations of the analyzed compounds. To assess the applicability and effectiveness of the hydrophobic DES, the validated method was applied to extract the studied drugs from rabbit plasma samples after oral administration of FLV alone and in combination with EMP. The pharmacokinetic parameters of FLV were calculated in both cases to investigate any changes and determine the need for dose adjustment.

A selective dual quenching sensor (EY/BG@CDs) for simultaneous monitoring of gentamicin and ketorolac levels in plasma: a highly efficient platform that caters to the needs of therapeutic drug monitoring.

This research work introduces a novel sensor that utilizes two fluorophores to enable simultaneous monitoring of gentamicin sulphate (GNT) and ketorolac tromethamine (KET). The innovative sensor is composed of carbon dots (CDs) derived from black grapes (BG) and eosin Y (EY) dye. The interaction between the studied drugs and EY/BG@CDs sensor components allows for their simultaneous detection where GNT quenches the fluorescence of EY at 535 nm without affecting the fluorescence of CDs, while KET quenches the fluorescence of BG@CDs at 385 nm without impacting EY fluorescence. The BG@CDs probe was successfully characterized using various techniques such as absorption spectrophotometry, spectrofluorimetry, TEM imaging, infrared spectroscopic analysis, and XRD analysis. The suggested methodology was observed to be highly sensitive for the simultaneous determination of GNT and KET in their spiked rabbit plasma samples, with wide linear ranges and low limit of detection (LOD) values. The studied drugs were extracted using a highly selective extraction method involving protein precipitation followed by mixed mode solid phase extraction using an Oasis WCX cartridge. The simultaneous determination of GNT and KET is essential due to the potential interactions between the studied drugs. Therefore, this analysis can be used to evaluate the necessity of dose monitoring and the potential adverse effects of co-administration of these drugs.

Temporal and spatial trends in lead levels in the blood and down of Black Stork nestlings in central Europe.

Young birds at an intensive growth stage are especially vulnerable to the deleterious effects of contaminants such as lead (Pb). This element negatively influences organs, development and even behavior, which can consequently lead to lower survival and reproductive success of the population. There was a suspicion that these mechanisms, along with other factors, retarded population growth of the Black Stork - still a heavily understudied species in respect to pollution, especially Pb. Therefore, we undertook a study concerning Pb concentrations in the down and blood of Black Stork nestlings from breeding grounds in central and southern Poland (Europe). To investigate the effects of Pb exposure on nestling condition, scale mass index and reduced glutathione levels were also studied, but results indicated that Pb did not influence either of these parameters. The highest blood Pb concentration reached 0.247 µg/g, while the highest down Pb concentrations was significantly higher reaching 4.95 µg/g. Concentrations in blood and down were not correlated with each other. Nest location and year of sampling were not influential for blood but were influential for down Pb concentrations. Relationships between Pb concentrations, habitat characteristics and proximity to emitters were not significant. Overall Pb concentrations in Black Stork nestlings were below the toxicity threshold and did not have negative effects on specimens studied. They were probably related to maternal exposure during migration, on stopover and breeding grounds as well as with food provided by parents.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

Insight into the biochemical and physiological mechanisms of nanoparticles-induced arsenic tolerance in bamboo.

Introduction: Arsenic (As) contamination in soil, sediments, and water poses a significant threat to the growth of bamboo plants. However, nanoparticles with high metal absorbance capacity can play a key role in the reduction of heavy metals toxicity in plants as well as maintaining their growth under toxicity. Methods: Hence, an in vitro experiment was conducted to determine the influence of three types of nanoparticles: 150 µM silicon nanoparticles (SiO2 NPs), 150 µM titanium nanoparticles (TiO2 NPs), and 150 µM zinc oxide nanoparticles (ZnO NPs) on As (150 µM and 250 µM) tolerance enhancement of a one-year-old bamboo species (Pleioblastus pygmaeus). Results and discussion: The results showed that while As at 150 µM and 250 µM significantly disrupted the plant growth by excessive generation of reactive oxygen species (ROS) components, and inducing cell membrane peroxidation, the addition of NPs increased both enzymatic and non-enzymatic antioxidant activities, upregulated glyoxalase defense system, and improved gas exchange parameters and photosynthetic pigments content, leading to the enhanced plant shoot and root dry weight. These were achieved by lowering levels of ROS, electrolyte leakage (EL), malondialdehyde (MDA), hydrogen peroxide (H2O2) and the superoxide radical ( O 2 • - ), as well as decreasing As accumulation in the plant organs. Thus, it might be concluded that ZnO NPs, SiO2NPs, and TiO2NPS alone or in combination can significantly increase the bamboo plant tolerance to As toxicity via key mechanisms, including induction of various antioxidants and glyoxalase defense systems, scavenging of ROS and methylglyoxal (MG), increasing phytochelatins production, reduction of As accumulation and translocation, and improving photosynthetic pigments under As toxicity. Additionally, the results showed that the combined application of 150 µM ZnO NPs, SiO2 NPs, and TiO2 NPs had the greatest effect on enhancing the plant tolerance to As at 150 µM and 250 µM.

Exploring the well-being of community pharmacy professionals, turnover intention and patient safety: Time to include operational responsibility.

Background: The COVID-19 pandemic added significant occupational pressures on community pharmacists. The objective of this research project was to investigate the level of distress and burnout among community pharmacy professionals and its association with their retention within their occupation as well as patient safety outcomes. Method: We conducted a cross-sectional study on 722 community pharmacy professionals from all Canadian provinces using an online survey, including scientifically validated measures. The data were analyzed using multiple regression analysis. Results: In Canada, 85% of community pharmacy professionals reported their mental health had suffered since the COVID-19 pandemic. Younger pharmacy professionals and those paid hourly reported a worsening level of mental health and an increasing level of turnover intention. Pharmacists with more dynamic/disrupted work schedules and those working for a large pharmacy chain (more than 25 pharmacies in Canada) reported lower levels of mental health quality. Pharmacy professionals working in pharmacies that are open more than 70 hours a week reported a lower level of patient safety culture. Pharmacists' mental health was the significant predictor of their turnover intention, implying a heightened risk to professional effectiveness and retention. Compassion satisfaction was positively associated with patient safety culture and safety behaviour, while compassion fatigue and secondary traumatic stress were significantly associated with pharmacists' level of risk-taking behaviours. Conclusion: This study emphasized the importance of prioritizing the mental health and well-being of community pharmacy professionals and demonstrated individual and systemic factors predicting the well-being and turnover intention of community pharmacists, as well as patient safety culture within their pharmacy. This research makes a case to consider actions to shift the monitoring focus from community pharmacists (also known as "individual responsibility") to community pharmacies (also known as "operational responsibility") for managing patient safety. Additionally, community pharmacists should be provided with the professional autonomy to affect their working conditions and alleviate the stress that has the potential to negatively affect the delivery of care.

Sodium Nitroprusside Improves Bamboo Resistance under Mn and Cr Toxicity with Stimulation of Antioxidants Activity, Relative Water Content, and Metal Translocation and Accumulation.

Sodium nitroprusside (SNP), as a single minuscule signaling molecule, has been employed to alleviate plant stress in recent years. This approach has a beneficial effect on the biological and physiological processes of plants. As a result, an in vitro tissue culture experiment was carried out to investigate the effect of high and low levels of SNP on the amelioration of manganese (Mn) and chromium (Cr) toxicity in a one-year-old bamboo plant, namely Pleioblastus pygmaea L. Five different concentrations of SNP were utilized as a nitric oxide (NO) donor (0, 50, 80, 150, 250, and 400 µM) in four replications of 150 µM Mn and 150 µM Cr. The results revealed that while 150 µM Mn and 150 µM Cr induced an over-generation of reactive oxygen species (ROS) compounds, enhancing plant membrane injury, electrolyte leakage (EL), and oxidation in bamboo species, the varying levels of SNP significantly increased antioxidant and non-antioxidant activities, proline (Pro), glutathione (GSH), and glycine betaine (GB) content, photosynthesis, and plant growth parameters, while also reducing heavy metal accumulation and translocation in the shoot and stem. This resulted in an increase in the plant's tolerance to Mn and Cr toxicity. Hence, it is inferred that NO-induced mechanisms boosted plant resistance to toxicity by increasing antioxidant capacity, inhibiting heavy metal accumulation in the aerial part of the plant, restricting heavy metal translocation from root to leaves, and enhancing the relative water content of leaves.

Conceptualizing the reporting of living systematic reviews.

OBJECTIVES: As part of an effort to develop an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for living systematic reviews (LSRs), we discuss conceptual issues relevant to the reporting of LSRs and highlight a few challenges. METHODS: Discussion of conceptual issues based on a scoping review of the literature and discussions among authors. RESULTS: We first briefly describe aspects of the LSR production process relevant to reporting. The production cycles differ by whether the literature surveillance identifies new evidence and whether newly identified evidence is judged to be consequential. This impacts the timing, content, and format of LSR versions. Second, we discuss four types of information that are specific to the reporting of LSRs: justification for adopting the living mode, LSR specific methods, changes between LSR versions, and LSR updating status. We also discuss the challenge of conveying changes between versions to the reader. Third, we describe two commonly used reporting formats of LSRs: full and partial reports. Although partial reports are easier to produce and publish, they lead to the scattering of information across different versions. Full reports ensure the completeness of reporting. We discuss the implications for the extension of the PRISMA 2020 statement for LSRs. CONCLUSION: We argue that a dynamic publication platform would facilitate complete and timely reporting of LSRs.

Cerebral amyloid angiopathy: clinical presentations and management challenges in the Australian context.

Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid-beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co-exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.

Innovative Detection of Testosterone Esters in Camel Hair: Unravelling the Mysteries of Dromedary Endocrinology.

Introduction: Doping and steroid use represent a serious threat to animal health and can even lead to their untimely and painful death. However, doping is an acute problem in today's animal racing world, particularly in camel racing. Testosterone and its ten esters (benzoate, valerate, isocaproate, hexahydrobenzoate, decanoate, undecanoate, laurate, enanthate, cypionate, and caproate) are of utmost importance, because when they are administered to animals it is difficult to measure them efficiently. The levels of testosterone and its esters in camels and other animals are typically determined using urine and blood tests. The aim of this study was to develop and validate a liquid chromatographic-mass spectrometric (LC-MS/MS) method to determine testosterone esters in camel hair, and to apply the validated method to determine testosterone esters in collected samples. To our knowledge, this is the first report of such research. Results and Discussion: The levels of testosterone and its ten derivatives, along with the cortisol-D4 internal standard, were optimised for LC-MS/MS analysis; however, only testosterone along with its seven esters (namely benzoate, valerate, isocaproate, hexahydrobenzoate, decanoate, undecanoate and laurate) could be validated in camel hair. Only five testosterone esters could be determined in camel hair samples; the concentrations were obtained as 10.5-14.9 pg/mg for valerate (in three camels), 12.5-151.6 pg/mg for hexahydrobenzoate (in six camels), 4.8-32.1 pg/mg for laurate (in five camels), 5.1 pg/mg decanoate (in one camel), and 8.35-169 pg/mg for testosterone (in all 24 camels). Interestingly, the three racing camels displayed high concentrations of testosterone (59.2-169 pg/mg, all three camels), laurate (4.8-14.5 pg/mg, two camels), hexahydrobenzoate (116 pg/mg, one camel), decanoate (5.1 pg/mg, one camel), and valerate (11.7 pg/mg, one camel). Methods: Camel hair samples were collected from 21 non-racing dromedary camels along with three racing camels in Al Ain, UAE; these were decontaminated, pulverised, sonicated, and extracted prior to analysis. An LC-MS/MS method was employed to determine the levels of testosterone esters in the hair samples. Conclusions: This novel camel-hair test procedure is accurate, sensitive, rapid, and robust. The findings reported in this study could be significant to evaluate racing camels for suspected doping offenses. Further controlled testosterone supplementation studies are required to evaluate individual esters' effects on camel health and diseases and on performance enhancement levels. This new hair test could promote further studies in doping control, toxicology, and pharmacology, as well as having other clinical applications relating to camel health, injury, and disease.

Benzylaminopurine and Abscisic Acid Mitigates Cadmium and Copper Toxicity by Boosting Plant Growth, Antioxidant Capacity, Reducing Metal Accumulation and Translocation in Bamboo [Pleioblastus pygmaeus (Miq.)] Plants.

An in vitro experiment was conducted to determine the influence of phytohormones on the enhancement of bamboo resistance to heavy metal exposure (Cd and Cu). To this end, one-year-old bamboo plants (Pleioblastus pygmaeus (Miq.) Nakai.) contaminated by 100 µM Cd and 100 µM Cu both individually and in combination were treated with 10 µM, 6-benzylaminopurine and 10 µM abscisic acid. The results revealed that while 100 µM Cd and 100 µM Cu accelerated plant cell death and decreased plant growth and development, 10 µM 6-benzylaminopurine and 10 µM abscisic acid, both individually and in combination, increased plant growth by boosting antioxidant activities, non-antioxidants indices, tyrosine ammonia-lyase activity (TAL), as well as phenylalanine ammonia-lyase activity (PAL). Moreover, this combination enhanced protein thiol, total thiol, non-protein, glycine betaine (GB), the content of proline (Pro), glutathione (GSH), photosynthetic pigments (Chlorophyll and Carotenoids), fluorescence parameters, dry weight in shoot and root, as well as length of the shoot. It was then concluded that 6-benzyl amino purine and abscisic acid, both individually and in combination, enhanced plant tolerance under Cd and Cu through several key mechanisms, including increased antioxidant activity, improved photosynthesis properties, and decreased metals accumulation and metal translocation from root to shoot.

Development of a Gas-Tight Syringe Headspace GC-FID Method for the Detection of Ethanol, and a Description of the Legal and Practical Framework for Its Analysis, in Samples of English and Welsh Motorists' Blood and Urine.

Ethanol is the most commonly used recreational drug worldwide. This study describes the development and validation of a headspace gas chromatography flame ionisation detection (HS-GC-FID) method using dual columns and detectors for simultaneous separation and quantitation. The use of a dual-column, dual-detector HS-GC-FID to quantitate ethanol is a common analytical technique in forensic toxicology; however, most analytical systems utilise pressure-balance injection rather than a simplified gas-tight syringe, as per this technique. This study is the first to develop and validate a technique that meets the specifications of the United Kingdom's requirements for road traffic toxicology testing using a Shimadzu GC-2014 gas-tight syringe. The calibration ranged from 10 to 400 mg/100 mL, with a target minimum linearity of r2 > 0.999, using tertiary butanol as the internal standard marker. The method has an expanded uncertainty at 99.73% confidence of 3.64% at 80 mg/100 mL, which is the blood alcohol limit for drink driving in England and Wales. In addition, at 200 mg%­the limit at which a custodial sentence may be imposed on the defendant­the expanded uncertainty was 1.95%. For both the 80 mg% and 200 mg% concentrations, no bias was present in the analytical method. This method displays sufficient separation for other alcohols, such as methanol, isopropanol, acetaldehyde, and acetone. The validation of this technique complies with the recommended laboratory guidelines set out by United Kingdom and Ireland Association of Forensic Toxicologists (UKIAFT), the recently issued Laboratory 51 guidelines by the United Kingdom Accreditation Service (UKAS), and the criteria set out by the California Code of Regulations (CCR), 17 CCR § 1220.1.

A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

Development and Validation of an HPLC-UV Method for the Quantification of 4'-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug-Drug Interaction in Rat Liver Microsomes.

Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug−drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug−drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of the Cytochrome P450 enzyme activity leads to the withdrawal of the drug from the market. The aim of this paper was to develop and validate an HPLC-UV method for the quantification of 4'-hydroxydiclofenac as a CYP2C9 metabolite using salicylic acid as an inhibitor in rat liver microsomes. A CYP2C9 assay was developed and validated on the reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) using a low-pressure gradient elution programming at T = 30 °C, a wavelength of 282 nm, and a flow rate of 1 mL/min. 4'-hydroxydiclofenac demonstrated a good linearity (R2 > 0.99), good reproducibility, low detection, and quantitation limit, and the inter and intra-day precision met the ICH guidelines (<15%). 4'-hydroxydiclofenac was stable for three days and showed an acceptable accuracy and recovery (80−120%) within the ICH guidelines in a rat liver microsome sample. This method will be beneficial for future applications of the in vitro inhibitory effect of salicylic acid on the CYP2C9 enzyme activity in rat microsomes and the in vivo administration of salicylic acid in clinical trials.