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Scientific Reports Jul 2024Plants are valuable resources for drug discovery as they produce diverse bioactive compounds. However, the chemical diversity makes it difficult to predict the...
Plants are valuable resources for drug discovery as they produce diverse bioactive compounds. However, the chemical diversity makes it difficult to predict the biological activity of plant extracts via conventional chemometric methods. In this research, we propose a new computational model that integrates chemical composition data with structure-based chemical ontology. For a model validation, two training datasets were prepared from literature on antibacterial essential oils to classify active/inactive oils. Random forest classifiers constructed from the data showed improved prediction performance in both test datasets. Prior feature selection using hierarchical information criterion further improved the performance. Furthermore, an antibacterial assay using a standard strain of Staphylococcus aureus revealed that the classifier correctly predicted the activity of commercially available oils with an accuracy of 83% (= 10/12). The results of this study indicate that machine learning of chemical composition data integrated with chemical ontology can be a highly efficient approach for exploring bioactive plant extracts.
Topics: Oils, Volatile; Anti-Bacterial Agents; Staphylococcus aureus; Machine Learning; Microbial Sensitivity Tests; Chemometrics; Plant Extracts
PubMed: 38951169
DOI: 10.1038/s41598-024-65882-9 -
BMJ Open Jul 2024Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal...
INTRODUCTION
Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.
METHODS AND ANALYSIS
A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
ETHICS AND DISSEMINATION
This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
TRIAL REGISTRATION NUMBER
Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.
Topics: Humans; Drug Monitoring; Anti-Bacterial Agents; Feasibility Studies; Critical Illness; beta-Lactams; Randomized Controlled Trials as Topic; Intensive Care Units
PubMed: 38951004
DOI: 10.1136/bmjopen-2023-083635 -
Drug and Therapeutics Bulletin Jul 2024Chronic obstructive pulmonary disease (COPD) is a common but underdiagnosed lung condition that is frequently managed inappropriately. It impacts poorest communities... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a common but underdiagnosed lung condition that is frequently managed inappropriately. It impacts poorest communities most, where health inequalities are greatest. New acute symptoms of breathlessness, cough, sputum production and wheeze should prompt clinical suspicion of underlying COPD in someone who is a current or ex-smoker (or has exposure to other risk factors) and be followed by referral for quality-assured spirometry once recovered. Management of COPD exacerbations in primary care includes use of short-acting bronchodilators if mild, and antibiotics and a short course of oral prednisolone if moderate/severe. Hospital at home schemes are safe and effective and should be considered for some patients exacerbating in the community; these are increasingly supported by remote monitoring ('virtual wards'). New or worsening hypoxia is an indication for hospital admission and therefore oxygen saturation monitoring is an important part of exacerbation management; clinicians should be aware of patient safety alerts around use of pulse oximeters. Exacerbations drive poor health status and lung function decline and therefore asking about exacerbation frequency at planned reviews and taking action to reduce these is an important part of long-term COPD care. An exacerbation is an opportunity to ensure that fundamentals of good care are addressed. Patients should be supported to understand and act on exacerbations through a supported self-management plan; prompt treatment is beneficial but should be balanced by careful antibiotic and corticosteroid stewardship. COPD rescue packs on repeat prescription are not recommended.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Primary Health Care; Bronchodilator Agents; Anti-Bacterial Agents; Disease Progression
PubMed: 38950975
DOI: 10.1136/dtb.2023.000026 -
PloS One 2024Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be...
Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be tested for cytotoxicity before being administered to patients. The aim of this study was to develop a suitable and biorelevant in vitro cytotoxicity assay for ES biomaterials (e.g. wound dressings). We compared different in vitro cytotoxicity assays, and our model wound dressing was made from polycaprolactone and polyethylene oxide and contained chloramphenicol as the active pharmaceutical ingredient. Baby Hamster Kidney cells (BHK-21), human primary fibroblasts and MTS assays together with real-time cell analysis were selected. The extract exposure and direct contact safety evaluation setups were tested together with microscopic techniques. We found that while extract exposure assays are suitable for the initial testing, the biocompatibility of the biomaterial is revealed in in vitro direct contact assays where cell interactions with the ES wound dressing are evaluated. We observed significant differences in the experimental outcome, caused by the experimental set up modification such as cell line choice, cell medium and controls used, conducting the phosphate buffer washing step or not. A more detailed technical protocol for the in vitro cytotoxicity assessment of ES wound dressings was developed.
Topics: Animals; Wound Healing; Biocompatible Materials; Humans; Bandages; Cell Line; Materials Testing; Cricetinae; Polyesters; Fibroblasts; Anti-Infective Agents; Polyethylene Glycols; Chloramphenicol
PubMed: 38950036
DOI: 10.1371/journal.pone.0305137 -
Dental and Medical Problems 2024Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and...
BACKGROUND
Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and antibacterial properties. Efforts have been made to improve the strength of their bond to demineralized enamel, fluoride release and antibacterial properties by adding nanoparticles of chitosan, which seems to be a promising method.
OBJECTIVES
The aim of the present study was to assess the antibacterial effect, the microshear bond strength (μSBS) to enamel at the WSL area, and the fluoride and nano-chitosan release after modifying the polyacrylic acid liquid phase of a traditional GIC with different nano-chitosan volumes.
MATERIAL AND METHODS
A total of 120 samples were prepared, and then divided into 4 groups (n = 30): G1 - non-modified GIC, which served as a control group, while G2, G3 and G4 were modified with different nano-chitosan volumes (50%, 100% and 150%, respectively). Microshear bond strength was assessed using a universal testing machine (UTM) after storage in distilled water for 24 h. Fluoride and nanochitosan release was measured with the use of spectrophotometers at different time points (initially, and at 1 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, and 6 weeks) after storage in distilled water. The antibacterial effect against the Streptococcus aureus strain was assessed with the agar diffusion test. The data was statistically analyzed.
RESULTS
After 24-hour storage, G2 recorded a slight, yet non-significant, increase in the μSBS values (4.1 ±0.94 MPa) as compared to G1 (3.9 ±1.30 MPa). With regard to fluoride release, the amount recorded for G1 was significantly greater at the end of the 24-hour storage period (0.70 ±0.30 μmf/cm2) than modified nano-chitosan GIC groups; G1 was followed by G4 (0.54 ±0.34 μmf/cm2). The highest amount of nano-chitosan release after 24-hour storage was noted for G3 (0.85 ±0.00 μmf/cm2). The highest inhibition zone value was recorded for G2.
CONCLUSIONS
Glass-ionomer cement modified with 50% nano-chitosan was shown to positively affect μSBS and the antibacterial effect, while modification with 150% nano-chitosan significantly increased fluoride release.
Topics: Chitosan; Anti-Bacterial Agents; Glass Ionomer Cements; Dental Caries; In Vitro Techniques; Fluorides; Humans; Nanoparticles; Shear Strength; Dental Enamel; Materials Testing; Dental Bonding
PubMed: 38949834
DOI: 10.17219/dmp/158835 -
Methods in Molecular Biology (Clifton,... 2024Genomic sequencing has revolutionized microbial typing methods and transformed high-throughput methods in reference, clinical, and research laboratories. The detection...
Genomic sequencing has revolutionized microbial typing methods and transformed high-throughput methods in reference, clinical, and research laboratories. The detection of antimicrobial-resistant (AMR) determinants using genomic methods can provide valuable information on the emergence of resistance. Here we describe an approach to detecting AMR determinants using an open access and freely available platform which does not require bioinformatic expertise.
Topics: Whole Genome Sequencing; Drug Resistance, Bacterial; Genome, Bacterial; Computational Biology; Humans; Anti-Bacterial Agents; Genomics; Software; Bacteria; High-Throughput Nucleotide Sequencing
PubMed: 38949713
DOI: 10.1007/978-1-0716-3981-8_19 -
Methods in Molecular Biology (Clifton,... 2024Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many...
Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many first- and second-line anti-tuberculosis drugs. However, bioinformatic pipelines and mutation catalogs to predict antimicrobial resistances in MTBC isolates are often customized and detailed protocols are difficult to access. Here, we provide a step-by-step workflow for the processing and interpretation of short-read sequencing data and give an overview of available analysis pipelines.
Topics: Mycobacterium tuberculosis; Whole Genome Sequencing; Microbial Sensitivity Tests; Humans; Antitubercular Agents; Computational Biology; Genome, Bacterial; Drug Resistance, Bacterial; Mutation; Tuberculosis
PubMed: 38949712
DOI: 10.1007/978-1-0716-3981-8_18 -
Methods in Molecular Biology (Clifton,... 2024Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in...
Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in many countries. WGS protocols usually start with the preparation of a DNA-library: the critical first step in the process. A DNA-library represents the genomic content of a DNA sample and consists of unique short DNA fragments. Although available DNA-library protocols come with manufacturer instructions, details of the entire process, including quality controls, instrument parameters, and run evaluations, often need to be developed and customized by each laboratory to implement WGS technology effectively. Here, we provide a detailed workflow for a DNA-library preparation based on an adapted Illumina protocol optimized for the reduction of reagent costs.
Topics: Mycobacterium tuberculosis; Whole Genome Sequencing; Microbial Sensitivity Tests; Genome, Bacterial; Humans; Antitubercular Agents; Gene Library; DNA, Bacterial; Tuberculosis; High-Throughput Nucleotide Sequencing
PubMed: 38949711
DOI: 10.1007/978-1-0716-3981-8_17 -
Methods in Molecular Biology (Clifton,... 2024The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis...
The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.
Topics: Feces; Mycobacterium tuberculosis; Humans; Bacterial Load; Tuberculosis; Antitubercular Agents; DNA, Bacterial; Sputum
PubMed: 38949709
DOI: 10.1007/978-1-0716-3981-8_15 -
Methods in Molecular Biology (Clifton,... 2024Antibiotic resistance is a global challenge likely to cost trillions of dollars in excess costs in the health system and more importantly, millions of lives every year.... (Review)
Review
Antibiotic resistance is a global challenge likely to cost trillions of dollars in excess costs in the health system and more importantly, millions of lives every year. A major driver of resistance is the absence of susceptibility testing at the time a healthcare worker needs to prescribe an antimicrobial. The effect is that many prescriptions are unintentionally wasted and expose mutable organisms to antibiotics increasing the risk of resistance emerging. Often simplistic solutions are applied to this growing issue, such as a naïve drive to increase the speed of drug susceptibility testing. This puts a spotlight on a technological solution and there is a multiplicity of such candidate DST tests in development. Yet, if we do not define the necessary information and the speed at which it needs to be available in the clinical decision-making progress as well as the necessary integration into clinical pathways, then little progress will be made. In this chapter, we place the technological challenge in a clinical and systems context. Further, we will review the landscape of some promising technologies that are emerging and attempt to place them in the clinic where they will have to succeed.
Topics: Anti-Bacterial Agents; Microbial Sensitivity Tests; Humans; Drug Resistance, Bacterial; Bacteria
PubMed: 38949707
DOI: 10.1007/978-1-0716-3981-8_13