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The Journal of Craniofacial Surgery Jul 2024Craniomaxillofacial (CMF) fractures present significant challenges for plastic surgeons due to their intricate nature. Conventional methods such as autologous bone...
Craniomaxillofacial (CMF) fractures present significant challenges for plastic surgeons due to their intricate nature. Conventional methods such as autologous bone grafts have limitations, necessitating advancements in reconstructive surgery techniques. This study reviewed the use of three-dimensional printing for CMF trauma reconstruction using human studies. A systematic search of PubMed, EMBASE, and Google Scholar was conducted in February 2024 for case reports, case series, and clinical trials related to CMF trauma reconstruction using three-dimensional printing technology. The authors' systematic review included 20 studies and a total of 170 participants with CMF bone defects. In general, the authors observed low bias risk in analyzed case reports and series, serious bias risk in nonrandomized controlled trials, and moderate bias risk in randomized controlled trials. The printed objects included CMF structure model prototypes, patient-specific implants, and other custom surgical devices. Studies reveal successful outcomes, including restored facial symmetry and function, restored orbital occlusion, resolved enophthalmos and diplopia, achieved cosmetically symmetrical lower face reconstruction, and precise fitting of surgical devices, enhancing patient and surgeon comfort. However, complications such as local infection, implant exposure, and persistent diplopia were reported. Three-dimensional printed devices reduced surgery time but increased preparation time and production costs. In-house production options could mitigate these time and cost expenditures. Three-dimensional printing holds potential in CMF trauma reconstruction, addressing both functional and esthetic restoration. Nevertheless, challenges persist in implementing this advanced technology in resource-limited environments.
PubMed: 38958985
DOI: 10.1097/SCS.0000000000010451 -
European Journal of Drug Metabolism and... Jul 2024The identification of substrates for solute carriers (SLCs) handling drugs is an important challenge, owing to the major implication of these plasma membrane...
The identification of substrates for solute carriers (SLCs) handling drugs is an important challenge, owing to the major implication of these plasma membrane transporters in pharmacokinetics and drug-drug interactions. In this context, the competitive counterflow (CCF) assay has been proposed as a practical and less expensive approach than the reference functional uptake assays for discriminating SLC substrates and non-substrates. The present article was designed to summarize and discuss key-findings about the CCF assay, including its principle, applications, challenges and limits, and perspectives. The CCF assay is based on the decrease of the steady-state accumulation of a tracer substrate in SLC-positive cells, caused by candidate substrates. Reviewed data highlight the fact that the CCF assay has been used to identify substrates and non-substrates for organic cation transporters (OCTs), organic anion transporters (OATs), and organic anion transporting polypeptides (OATPs). The performance values of the CCF assay, calculated from available CCF study data compared with reference functional uptake assay data, are, however, rather mitigated, indicating that the predictability of the CCF method for assessing SLC-mediated transportability of drugs is currently not optimal. Further studies, notably aimed at standardizing the CCF assay and developing CCF-based high-throughput approaches, are therefore required in order to fully precise the interest and relevance of the CCF assay for identifying substrates and non-substrates of SLCs.
PubMed: 38958896
DOI: 10.1007/s13318-024-00902-7 -
Monash Bioethics Review Jul 2024This paper contributes to the growing discussion about how to mitigate pharmaceutical pollution, which is a threat to human, animal, and environmental health as well as...
This paper contributes to the growing discussion about how to mitigate pharmaceutical pollution, which is a threat to human, animal, and environmental health as well as a potential driver of antimicrobial resistance. It identifies market approval of pharmaceuticals as one of the most powerful ways to shape producer behavior and highlights that applying this tool raises ethical issues given that it might impact patients' access to medicines. The paper identifies seven different policy options that progressively give environmental considerations increased priority in the approval process, identifies ethically relevant interests affected by such policies, and makes explicit tensions and necessary tradeoffs between these interests. While arguing that the current European regulation gives insufficient weight to environmental considerations, the paper highlights concerns with the strongest policy options, on the grounds that these may very well endanger patients' access to effective medication.
PubMed: 38958879
DOI: 10.1007/s40592-024-00195-1 -
Cardiovascular Drugs and Therapy Jul 2024The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer... (Review)
Review
The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.
PubMed: 38958827
DOI: 10.1007/s10557-024-07604-x -
Cell Biology and Toxicology Jul 2024The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have...
The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.
Topics: Zinc Oxide; Animals; Oxidative Stress; Chick Embryo; Embryonic Development; Mice; Neural Tube; Humans; Neural Tube Defects; Reactive Oxygen Species; Apoptosis; Cell Death; Female; Mitochondria; Metal Nanoparticles; Autophagy; Cell Line, Tumor; Nanoparticles
PubMed: 38958792
DOI: 10.1007/s10565-024-09894-1 -
Supportive Care in Cancer : Official... Jul 2024Post-traumatic growth can improve the quality of life of cancer survivors. The objective of this study was to investigate post-traumatic growth heterogeneity trajectory...
OBJECTIVES
Post-traumatic growth can improve the quality of life of cancer survivors. The objective of this study was to investigate post-traumatic growth heterogeneity trajectory in perioperative gastric cancer survivors, and to identify characteristics that predict membership for each trajectory.
METHODS
Gastric cancer survivors (n = 403) were recruited before surgery, their baseline assessment (including post-traumatic growth and related characteristics) was completed, and post-traumatic growth levels were followed up on the day they left the intensive care unit, at discharge, and 1 month after discharge. Latent growth mixture mode was used to identify the heterogeneous trajectory of post-traumatic growth, and the core predictors of trajectory subtypes were explored using a decision tree model.
RESULTS
Three post-traumatic growth development trajectories were identified among gastric cancer survivors: stable high of PTG group (20.6%), fluctuation of PTG group (44.4%), persistent low of PTG group (35.0%). The decision tree model showed anxiety, coping style, and psychological resilience-which was the primary predictor-might be used to predict the PTG trajectory subtypes of gastric cancer survivors.
CONCLUSIONS
There was considerable variability in the experience of post-traumatic growth among gastric cancer survivors. Recognition of high-risk gastric cancer survivors who fall into the fluctuation or persistent low of PTG group and provision of psychological resilience-centered support might allow medical professionals to improve patients' post-traumatic growth and mitigate the impact of negative outcomes.
Topics: Humans; Stomach Neoplasms; Male; Female; Cancer Survivors; Middle Aged; Longitudinal Studies; Posttraumatic Growth, Psychological; Aged; Adult; Quality of Life; Adaptation, Psychological; Resilience, Psychological; Anxiety; Decision Trees
PubMed: 38958751
DOI: 10.1007/s00520-024-08697-8 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Pertussis toxin (PT) is a virulent factor produced by Bordetella pertussis, the causative agent of whooping cough. PT exerts its pathogenic effects by ADP-ribosylating...
Pertussis toxin (PT) is a virulent factor produced by Bordetella pertussis, the causative agent of whooping cough. PT exerts its pathogenic effects by ADP-ribosylating heterotrimeric G proteins, disrupting cellular signaling pathways. Here, we investigate the potential of two antiarrhythmic drugs, amiodarone and dronedarone, in mitigating PT-induced cellular intoxication. After binding to cells, PT is endocytosed, transported from the Golgi to the endoplasmic reticulum where the enzyme subunit PTS1 is released from the transport subunit of PT. PTS1 is translocated into the cytosol where it ADP-ribosylates inhibitory α-subunit of G-protein coupled receptors (Gαi). We showed that amiodarone and dronedarone protected CHO cells and human A549 cells from PT-intoxication by analyzing the ADP-ribosylation status of Gαi. Amiodarone had no effect on PT binding to cells or in vitro enzyme activity of PTS1 but reduced the signal of PTS1 in the cell suggesting that amiodarone interferes with intracellular transport of PTS1. Moreover, dronedarone mitigated the PT-mediated effect on cAMP signaling in a cell-based bioassay. Taken together, our findings underscore the inhibitory effects of amiodarone and dronedarone on PT-induced cellular intoxication, providing valuable insights into drug repurposing for infectious disease management.
PubMed: 38958734
DOI: 10.1007/s00210-024-03247-9 -
A Feeding Trial to Investigate Strategies to Mitigate the Impacts of Poisoning in Australian Cattle.Journal of Agricultural and Food... Jul 2024poisoning of cattle causes distinct symptoms and frequently death, attributable to the toxin simplexin. poisoning was induced via addition of ground plant to the...
poisoning of cattle causes distinct symptoms and frequently death, attributable to the toxin simplexin. poisoning was induced via addition of ground plant to the daily feed in a three-month trial with Droughtmaster steers. The trial tested four potential mitigation treatments, namely, biochar, activated biochar, bentonite, and a bacterial inoculum, and incorporated negative and positive control groups. All treatments tested were unable to prevent the development of simplexin poisoning effects. However, steers consuming a bentonite adsorbent together with showed lesser rates-of-decline for body weight ( < 0.05) and four hematological parameters ( < 0.02), compared to the positive control group fed only. Microbiome analysis revealed that despite displaying poisoning symptoms, the rumen microbial populations of animals receiving were very resilient, with dominant bacterial populations maintained over time. Unexpectedly, clinical edema developed in some animals up to 2 weeks after dosing was ceased.
PubMed: 38958707
DOI: 10.1021/acs.jafc.4c02082 -
PharmacoEconomics Jul 2024Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that...
Evaluating the Public Health and Health Economic Impacts of Baloxavir Marboxil and Oseltamivir for Influenza Pandemic Control in China: A Cost-Effectiveness Analysis Using a Linked Dynamic Transmission-Economic Evaluation Model.
BACKGROUND
Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment.
METHODS
We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted.
RESULTS
The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions.
CONCLUSIONS
Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden.
PubMed: 38958667
DOI: 10.1007/s40273-024-01412-9 -
The Journal of the Acoustical Society... Jul 2024This paper explores the application of deep reinforcement learning for autonomously designing noise-mitigating structures. Specifically, deep Q- and double deep...
This paper explores the application of deep reinforcement learning for autonomously designing noise-mitigating structures. Specifically, deep Q- and double deep Q-networks are employed to find material distributions that result in broadband noise mitigation for reflection and transmission problems. Unlike conventional deep learning approaches which require prior knowledge for data labeling, the double deep Q-network algorithm learns configurations that result in broadband noise mitigations without prior knowledge by utilizing pixel-based inputs. By employing unified hyperparameters and network architectures for transmission and reflection problems, the capability of the algorithms to generalize over different environments is demonstrated. In addition, a comparison with a genetic algorithm highlights the potential for generalized design in complex environments, despite the algorithms tending to predict local maxima. Furthermore, we examine the impact of hyperparameters and environment types on agent performance. The autonomous design approach offers generalized learning while avoiding restrictions to specific shapes or prior knowledge of the task.
PubMed: 38958582
DOI: 10.1121/10.0026474