-
Health Promotion Perspectives 2023Many studies have assessed the effect of music on driving. However, their results are very scattered and contradictory. Therefore, this systematic review is conducted to...
BACKGROUND
Many studies have assessed the effect of music on driving. However, their results are very scattered and contradictory. Therefore, this systematic review is conducted to determine the effect of music on driving performance and drivers' physiological and psychological indicators.
METHODS
Scopus, PubMed, and Web of Science databases were searched until July 2023. A manual search in Google Scholar for gray literature was conducted. The Simulation Research Rubric (SRR) tool was used to assess the reporting quality of the studies. Stata software (StataCorp, version 16) was used to perform a meta-analysis.
RESULTS
A total of 2650 records were identified. The findings of 19 studies were analyzed. Most of them were carried out in high-income countries (HICs) using simulators. The most frequently used music style was classic rock. The meta-analysis results indicated that music with high and medium volume increases the average driving speed, and music with low volume decreases it. Although music in every mood reduces the average reaction time, it positively reduces response delay and increases coherence. Music with high volume decreases the heart rate, but music with medium and low volume increases it. Listening to music increases the level of arousal and mental load.
CONCLUSION
It was concluded that, in some indicators, listening to music has adverse effects on driving. However, in many indicators, music has a positive impact on improving driving safety. It is better to choose appropriate music for different driving conditions and to train the drivers about it.
PubMed: 38235004
DOI: 10.34172/hpp.2023.32 -
Journal of Pharmacokinetics and... Oct 2023Enzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro...
Enzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro studies. A clinical drug-drug interaction (DDI) study between enzalutamide and digoxin, a typical P-gp substrate, suggested enzalutamide has weak inhibitory effect on P-gp substrates. Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, are dual substrates of CYP3A4 and P-gp, and hence it is recommended to avoid co-administration of these DOACs with combined P-gp and strong CYP3A inducers. Enzalutamide's net effect on P-gp and CYP3A for apixaban and rivaroxaban plasma exposures is of interest to physicians who treat patients for venous thromboembolism with prostate cancer. Accordingly, a physiologically-based pharmacokinetic (PBPK) analysis was performed to predict the magnitude of DDI on apixaban and rivaroxaban exposures in the presence of 160 mg once-daily dosing of enzalutamide. The PBPK models of enzalutamide and M2, a major metabolite of enzalutamide which also has potential to induce CYP3A and P-gp and inhibit P-gp, were developed and verified as perpetrators of CYP3A-and P-gp-mediated interaction. Simulation results predicted a 31% decrease in AUC and no change in C for apixaban and a 45% decrease in AUC and a 25% decrease in C for rivaroxaban when 160 mg multiple doses of enzalutamide were co-administered. In summary, enzalutamide is considered to decrease apixaban and rivaroxaban exposure through the combined effects of CYP3A induction and net P-gp inhibition. Concurrent use of these drugs warrants careful monitoring for efficacy and safety.
Topics: Male; Humans; Cytochrome P-450 CYP3A; Rivaroxaban; Drug Interactions; Pharmaceutical Preparations; Models, Biological
PubMed: 37344637
DOI: 10.1007/s10928-023-09867-7 -
European Journal of Pharmaceutical... Oct 2023Co-administration of Bruton's tyrosine kinase (BTK) inhibitors with nirmatrelvir/ritonavir is challenging because of potential drug-drug interactions (DDIs). However,...
OBJECTIVE
Co-administration of Bruton's tyrosine kinase (BTK) inhibitors with nirmatrelvir/ritonavir is challenging because of potential drug-drug interactions (DDIs). However, clinical trials specifically evaluating such DDIs are absent. To evaluate and quantify the DDIs between them and provide rational dose management strategies of BTK inhibitors, we conducted this study using physiologically-based pharmacokinetic (PBPK) models.
METHODS
Physicochemical properties and pharmacokinetic parameters were acquired from the published literature and databases. The PBPK models were developed using Simcyp® software. These models were validated by comparing with published literature values. The successfully validated PBPK models were used to simulate the plasma concentration-time profiles and DDIs in a virtual healthy population receiving BTK inhibitors alone or with ritonavir.
RESULTS
Simulated plasma concentration-time profiles and pharmacokinetic parameters of each drug were in agreement with clinically observed values from literatures. Ritonavir increased ibrutinib maximum plasma concentration (C) and the area under plasma concentration-time curve (AUC) 33- and 53.88-fold, respectively, increased zanubrutinib C and AUC 2.57- and 3.18-fold, respectively, and increased acalabrutinib C and AUC 3.85- and 6.54-fold, respectively. Based on our simulations, dose-adjustment strategies may consist of ibrutinib at 25 mg q48h, zanubrutinib at 80 mg twice-daily and acalabrutinib at 25 mg twice-daily with nirmatrelvir/ritonavir.
CONCLUSIONS
The PBPK models predicted the in vivo pharmacokinetics and the DDIs of BTK inhibitors and ritonavir. The prospective simulations not only provided scientific evidence regarding rational dosing management strategies when initiating nirmatrelvir/ritonavir therapy but also provided a reference for the design of clinical DDIs study that may save resources and time.
SUMMARY
Paxlovid could increase C and AUC of BTK inhibitors (ibrutinib, zanubrutinib and acalabrutinib), and dose adjustment strategy of ibrutinib (25 mg q48h), zanubrutinib (80 mg q12h) and acalabrutinib (25 mg q12h) should be considered when combination with nirmatrelvir/ritonavir.
Topics: Ritonavir; Models, Biological; Drug Interactions
PubMed: 37586436
DOI: 10.1016/j.ejps.2023.106564 -
Revista Brasileira de Ortopedia Aug 2023To evaluate the risk factors and outcomes in patients surgically treated for subaxial cervical spine injuries with respect of the timing of surgery and preoperative...
To evaluate the risk factors and outcomes in patients surgically treated for subaxial cervical spine injuries with respect of the timing of surgery and preoperative physiological parameters of the patient. 26 patients with sub-axial cervical spine fractures and dislocations were enrolled. Demographic data of patients, appropriate radiological investigation, and physiological parameters like respiratory rate, blood pressure, heart rate, PaO2 and ASIA impairment scale were documented. They were divided pre-operatively into 2 groups. Group U with patients having abnormal physiological parameters and Group S including patients having physiological parameters within normal range. They were further subdivided into early and late groups according to the timing of surgery as U , U S and S . All the patients were called for follow-up at 1, 6 and 12 months. 56 percent of patients in Group S had neurological improvement by one ASIA grade and a good outcome irrespective of the timing of surgery. Patients in Group U having unstable physiological parameters and undergoing early surgical intervention had poor outcomes. This study concludes that early surgical intervention in physiologically unstable patients had a strong association as a risk factor in the final outcome of the patients in terms of mortality and morbidity. Also, no positive association of improvement in physiologically stable patients with respect to the timing of surgery could be established.
PubMed: 37663183
DOI: 10.1055/s-0043-1772240 -
International Journal of Molecular... Mar 2024Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence... (Review)
Review
Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence parallel stages of reproductive aging and occur alongside aging-related changes in the body. Alterations in the endocrine pathways accompany and often predate the physiologic changes of aging, and interactions of these processes are increasingly being recognized as contributory to the progression of senescence. Our goal for this review is to examine, in aging women, the complex interplay between the endocrinology of menopause transition and post-menopause, and the metabolic transition, the hallmark being an increasing tendency towards central adiposity that begins in tandem with reproductive aging and is often exacerbated post menopause. For the purpose of this review, our choice of the terms 'female' and 'woman' refer to genetic females.
Topics: Female; Humans; Adiposity; Aging; Menopause; Postmenopause; Reproduction; Obesity
PubMed: 38474226
DOI: 10.3390/ijms25052972 -
Scientific Reports Jul 2023Alveolar type 2 epithelial cells (AT2s) derived from human induced pluripotent stem cells (iAT2s) have rapidly contributed to our understanding of AT2 function and...
Alveolar type 2 epithelial cells (AT2s) derived from human induced pluripotent stem cells (iAT2s) have rapidly contributed to our understanding of AT2 function and disease. However, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse tissue, it is unclear how a physiologically relevant matrix will impact iAT2s phenotype. As extracellular matrix (ECM) is recognized as a vital component in directing cellular function and differentiation, we sought to derive hydrogels from decellularized human lung alveolar-enriched ECM (aECM) to provide an ex vivo model to characterize the role of physiologically relevant ECM on iAT2 phenotype. We demonstrate aECM hydrogels retain critical in situ ECM components, including structural and basement membrane proteins. While aECM hydrogels facilitate iAT2 proliferation and alveolosphere formation, a subset of iAT2s rapidly change morphology to thin and elongated ring-like cells. This morphological change correlates with upregulation of recently described iAT2-derived transitional cell state genetic markers. As such, we demonstrate a potentially underappreciated role of physiologically relevant aECM in iAT2 differentiation.
Topics: Humans; Mice; Animals; Hydrogels; Induced Pluripotent Stem Cells; Extracellular Matrix; Alveolar Epithelial Cells; Cell Differentiation; Epithelial Cells
PubMed: 37491483
DOI: 10.1038/s41598-023-37685-x -
Frontiers in Physiology 2023To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of... (Review)
Review
To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of pregnancy (ICP) when maternal serum BA levels reach very high concentrations (>100 μM). Generally, the placenta is believed to serve as a protective barrier avoiding exposure of the growing fetus to excessive amounts of maternal BAs that might cause detrimental effects (e.g., intrauterine growth restriction and/or increased vulnerability to metabolic diseases). However, little is known about the precise role of the placenta in BA biosynthesis, transport, and metabolism in healthy pregnancies when serum BAs are at physiological levels (i.e., low maternal and high fetal BA concentrations). It is well known that primary BAs are synthesized from cholesterol in the liver and are later modified to secondary BA species by colonic bacteria. Besides the liver, BA synthesis in extrahepatic sites such as the brain elicits neuroprotective actions through inhibition of apoptosis as well as oxidative and endoplasmic reticulum stress. Even though historically BAs were thought to be only "detergent molecules" required for intestinal absorption of dietary fats, they are nowadays acknowledged as full signaling molecules. They modulate a myriad of signaling pathways with functional consequences on essential processes such as gluconeogenesis -one of the principal energy sources of the fetus- and cellular proliferation. The current manuscript discusses the potential multipotent roles of physiologically circulating BAs on developmental processes during gestation and provides a novel perspective in terms of the importance of the placenta as a previously unknown source of BAs. Since the principle "not too much, not too little" applicable to other signaling molecules may be also true for BAs, the risks associated with fetal exposure to excessive levels of BAs are discussed.
PubMed: 37546542
DOI: 10.3389/fphys.2023.1213757 -
Nursing Open Aug 2023To describe the frequencies of physiologic monitor clinical alarms and to investigate nurses' perceptions and practices regarding clinical alarms in ICUs. (Observational Study)
Observational Study
AIM
To describe the frequencies of physiologic monitor clinical alarms and to investigate nurses' perceptions and practices regarding clinical alarms in ICUs.
DESIGN
A descriptive study.
METHODS
A 24-h continuous nonparticipant observation study was conducted in ICU. Observers observed and recorded the occurrence time, detail information when electrocardiogram monitor alarms triggered. And a cross-sectional study was conducted among ICU nurses by convenience sampling, using the general information questionnaire and the Chinese version of clinical alarms survey questionnaire for medical devices. Data analysis was performed using SPSS 23.
RESULTS
A total of 13,829 physiologic monitor clinical alarms were recorded in 14-day observation and 1191 ICU nurses responded to the survey. Most nurses agreed or strongly agreed the sensitivity to alarms and responded quickly (81.28%), smart alarm systems (74.56%), alarm notification systems (72.04%) and set up alarm administrators (59.45%) were useful to improve alarm management, while frequent nuisance alarms disrupted patients care (62.47%) and reduced nurses' trust in alarms (49.03%), environmental noise interfered with nurses' recognition of the alarms (49.12%) and not everyone received education of alarm systems (64.65%).
CONCLUSIONS
Physiological monitor alarms occur frequently in ICU, and it is necessary to formulate or further optimize alarm management measures. It is recommended to use smart medical devices and alarm notification systems, formulate and implement standardized alarm management policies and norms, and strengthen alarm management education and training, so as to improve the nursing quality and patient safety.
PATIENT OR PUBLIC CONTRIBUTION
The patients in the observation study included all patients admitted to the ICU during the observation period. The nurses in the survey study were conveniently selected through an online survey.
Topics: Humans; Clinical Alarms; Cross-Sectional Studies; Intensive Care Units; Monitoring, Physiologic; Nurses
PubMed: 37101342
DOI: 10.1002/nop2.1792 -
Scientific Reports Sep 2023Both machine learning and physiologically-based pharmacokinetic models are becoming essential components of the drug development process. Integrating the predictive...
Both machine learning and physiologically-based pharmacokinetic models are becoming essential components of the drug development process. Integrating the predictive capabilities of physiologically-based pharmacokinetic (PBPK) models within machine learning (ML) pipelines could offer significant benefits in improving the accuracy and scope of drug screening and evaluation procedures. Here, we describe the development and testing of a self-contained machine learning module capable of faithfully recapitulating summary pharmacokinetic (PK) parameters produced by a full PBPK model, given a set of input drug-specific and regimen-specific information. Because of its widespread use in characterizing the disposition of orally administered drugs, the PBPK model chosen to demonstrate the methodology was an open-source implementation of a state-of-the-art compartmental and transit model called OpenCAT. The model was tested for drug formulations spanning a large range of solubility and absorption characteristics, and was evaluated for concordance against predictions of OpenCAT and relevant experimental data. In general, the values predicted by the ML models were within 20% of those of the PBPK model across the range of drug and formulation properties. However, summary PK parameter predictions from both the ML model and full PBPK model were occasionally poor with respect to those derived from experiments, suggesting deficiencies in the underlying PBPK model.
Topics: Drug Evaluation, Preclinical; Machine Learning; Solubility
PubMed: 37696914
DOI: 10.1038/s41598-023-42165-3 -
The American Journal of Clinical... Mar 2024Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food... (Review)
Review
Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient-sensing via transporters and G-protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity/overweight (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacologic preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM. This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition, and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed. Some studies showed diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared with those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion. The results presented in this review highlight the potential of nutritional and physiologic stimulation of GLP-1 secretion. Further research on fasting and postprandial GLP-1 concentrations and the resulting metabolic consequences under different metabolic conditions is needed.
Topics: Adult; Humans; Glucagon-Like Peptide 1; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Insulin; Blood Glucose; Overweight; Diet; Fasting; Glucose Intolerance; Obesity; Postprandial Period
PubMed: 38218319
DOI: 10.1016/j.ajcnut.2024.01.007