Search Results (19,088)

A foundation pit is constructed in the floodplain of Yangtze River, and a deep and thick layer of large-particle pebble gravel exists below the base slab, thus forming a connected supply channel with the adjacent Yangtze River. The large water volume, high water pressure, and strong permeability of this layer bring great risks to the foundation pit construction. In view of the fact that conventional waterproof curtain construction technologies such as the deep mixing column and high-pressure jet grouting column cannot meet the engineering requirements under these kinds of geological and environmental conditions, a new waterproof curtain construction technology that combines the trenching technology of the diaphragm wall with the TRD (Trench cutting Remixing Deep wall) technology is proposed, i.e., the trenching-and-replacing-style TRD technology, as well as the construction process of this technology, is presented. After the waterproof curtain is built using the proposed technology, the strength, integrity, uniformity, and service performance of the waterproof curtain wall are tested and evaluated by the comprehensive methods of coring, borehole television imaging, resistivity CT, and a group well pumping test. The results show that the proposed technology overcomes the adverse effects of underlying large-particle pebble gravel layer, and the waterproof curtain built by it effectively cuts off the hydraulic connection inside and outside the pit. The technical proposal can provide useful references for similar projects. Full article

Background: Vitamin C has been used as an antioxidant and has been proven effective in boosting immunity in different diseases, including coronavirus disease (COVID-19). An increasing awareness was directed to the role of intravenous vitamin C in COVID-19. Methods: In this study, we aimed to assess the safety of high-dose intravenous vitamin C added to the conventional regimens for patients with different stages of COVID-19. An open-label clinical trial was conducted on patients with COVID-19. One hundred four patients underwent high-dose intravenous administration of vitamin C (in addition to conventional therapy), precisely 10 g in 250 cc of saline solution in slow infusion (60 drops/min) for three consecutive days. At the same time, 42 patients took the standard-of-care therapy. Results: This study showed the safety of high-dose intravenous administration of vitamin C. No adverse reactions were found. When we evaluated the renal function indices and estimated the glomerular filtration rate (eGRF, calculated with the CKD-EPI Creatinine Equation) as the main side effect and contraindication related to chronic renal failure, no statistically significant differences between the two groups were found. High-dose vitamin C treatment was not associated with a statistically significant reduction in mortality and admission to the intensive care unit, even if the result was bound to the statistical significance. On the contrary, age was independently associated with admission to the intensive care unit and in-hospital mortality as well as noninvasive ventilation (N.I.V.) and continuous positive airway pressure (CPAP) (OR 2.17, 95% CI 1.41–3.35; OR 7.50, 95% CI 1.97–28.54; OR 8.84, 95% CI 2.62–29.88, respectively). When considering the length of hospital stay, treatment with high-dose vitamin C predicts shorter hospitalization (OR −4.95 CI −0.21–−9.69). Conclusions: Our findings showed that an intravenous high dose of vitamin C is configured as a safe and promising therapy for patients with moderate to severe COVID-19. Full article

Background: Fresh frozen plasma (FFP) transfusions have been the mainstay of hemostatic intervention for the treatment of bleeding and coagulation abnormalities arising during liver transplantation (LT) for decades. However, numerous clinical studies showed that FFP has many side effects, including the risk of pathogen transmission, transfusion-associated circulatory overload (TACO), transfusion-related immunomodulation (TRIM), and transfusion-related acute lung injury (TRALI). These adverse events are particularly challenging in patients undergoing LT, who often suffer from severe portal hypertension, poor renal function and coexisting cardiac disease.The aims of this review are to summarize the pharmacological properties of currently available PCCs, to represent the theoretical benefits and the possible risks related to the use of these drugs in patients undergoing LT, and, finally, to review the current literature on the topic in order to highlight the evidence that currently supports PCC use in LT patients. Methods: The current literature on the topic was reviewed in order to highlight the evidence that currently supports PCC use in LT patients. Results: Prothrombin complex concentrates (PCCs) may offer several advantages when compared to FFP. Indeed, PCCs have been shown to reduce the risk of TACO, which during liver transplantation may deteriorate portal hypertension, increase intraoperative bleeding, and possibly reduce survival rates. One of the major concerns for PCC use is thrombogenicity. However, currently available PCCs are much safer as they contain inactivated forms of the vitamin K-dependent coagulation factors and protein C, protein S, antithrombin and/or heparin. Nowadays, the use of PCCs to correct coagulation abnormalities that occur during LT is an increasingly widespread practice. However, it is not yet clear what level of evidence supports this practice, and what the risks associated with it are. Conclusions: Administration of PCC in LT patients to correct haemostatic abnormalities seems to be well-tolerated, but the relationship between PCC use and thromboembolic events in the postoperative period remains unclear. Adequately powered, methodologically sound trials are urgently required for more definitive conclusions about the efficacy and safety of PCCs in a broad phenotype of LT recipients. Full article

While genotoxic chemotherapeutic agents are among the most effective tools to combat cancer, they are often associated with severe adverse effects caused by indiscriminate DNA damage in non-tumor tissue as well as increased risk of secondary carcinogenesis. This study builds on our previous work demonstrating that the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 elicits a non-canonical DNA damage response and our discovery of a critical role for Topoisomerase 2α (Top2α) in the initiation of Pol I-dependent transcription. Here, we identify Top2α as a mediator of CX-5461 response in the murine Eµ-Myc B lymphoma model whereby sensitivity to CX-5461 is dependent on cellular Top2α expression/activity. Most strikingly, and in contrast to canonical Top2α poisons, we found that the Top2α-dependent DNA damage induced by CX-5461 is preferentially localized at the ribosomal DNA (rDNA) promoter region, thereby highlighting CX-5461 as a loci-specific DNA damaging agent. This mechanism underpins the efficacy of CX-5461 against certain types of cancer and can be used to develop effective non-genotoxic anticancer drugs. Full article

Microbial communities are known to play an important role in maintaining ecological balance and can be used as an indicator for assessing environmental pollution. Numerous studies have revealed that air pollution can alter the structure of microbial communities, which may increase health risks. Nevertheless, the relationships between microbial communities and particulate matter (PM) caused by air pollution in terms of health risk assessment are not well understood. This study aimed to validate the influences of PM chemical compositions on microbial communities and assess the associated health risks. Our results, based on similarity analysis, revealed that the stability structure of the microbial communities had a similarity greater than 73%. In addition, the altered richness and diversity of microbial communities were significantly associated with PM chemical compositions. Volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) exerted a positive influence on microbial communities in different environmental variables. Additionally, a stronger linear correlation was observed between hydroxyl radicals (·OH) and the richness of microbial communities. All estimated health risks from PM chemical compositions, calculated under different environmental variables, significantly exceeded the acceptable level by a factor of more than 49. Cr and 1,2-Dibromoethane displayed dual adverse effects of non-carcinogenic and carcinogenic risks. Overall, the study provides insights into the fundamental mechanisms of the variability in microbial communities driven by PM, which may support the crucial role of PM chemical compositions in the risk of microorganisms in the atmospheric environment. Full article

The formation of an aneurysm in the false lumen (FL) is a long-term complication in a significant percentage of type B aortic dissection (AD) patients. The ability to predict which patients are likely to progress to aneurysm formation is key to justifying the risks of interventional therapy. The investigation of patient-specific hemodynamics has the potential to enable a patient-tailored approach to improve prognosis by guiding disease management for type B dissection. CFD-derived hemodynamic descriptors and geometric features were used to retrospectively assess individual aortas for a population of residual type B AD patients and analyze correlations with known outcomes (i.e., rapid aortic growth, death). The results highlight great variability in flow patterns and hemodynamic descriptors. A rapid aortic expansion was found to be associated with a larger FL. Time-averaged wall shear stress at the tear region emerged as a possible indicator of the dynamics of flow exchange between lumens and its effect on the evolution of individual aortas. High FL flow rate and tortuosity were associated with adverse outcomes suggesting a role as indicators of risk. AD induces complex changes in vessel geometry and hemodynamics. The reported findings emphasize the need for a patient-tailored approach when evaluating uncomplicated type B AD patients and show the potential of CFD-derived hemodynamics to complement anatomical assessment and help disease management. Full article

Nanomaterials have been extensively used in the biomedical field due to their unique physical and chemical properties. They promise wide applications in the diagnosis, prevention, and treatment of diseases. Nanodrugs are generally transported to target tissues or organs by coupling targeting molecules or enhanced permeability and retention effect (EPR) passively. As intravenous injection is the most common means of administration of nanomedicine, the transport process inevitably involves the interactions between nanoparticles (NPs) and blood cells. Platelets are known to not only play a critical role in normal coagulation by performing adhesion, aggregation, release, and contraction functions, but also be associated with pathological thrombosis, tumor metastasis, inflammation, and immune reactions, making it necessary to investigate the effects of NPs on platelet function during transport, particularly the way in which their physical and chemical properties determine their interaction with platelets and the underlying mechanisms by which they activate and induce platelet aggregation. However, such data are lacking. This review is intended to summarize the effects of NPs on platelet activation, aggregation, release, and apoptosis, as well as their effects on membrane proteins and morphology in order to shed light on such key issues as how to reduce their adverse reactions in the blood system, which should be taken into consideration in NP engineering. Full article

Colorectal cancer (CRC) is a significant public health challenge, with 5-fluorouracil (5-FU) resistance being a major obstacle to effective treatment. Despite advancements, resistance to 5-FU remains formidable due to complex mechanisms such as alterations in drug transport, evasion of apoptosis, dysregulation of cell cycle dynamics, tumor microenvironment (TME) interactions, and extracellular vesicle (EV)-mediated resistance pathways. Traditional chemotherapy often results in high toxicity, highlighting the need for alternative approaches with better efficacy and safety. Phytochemicals (PCs) and EVs offer promising CRC therapeutic strategies. PCs, derived from natural sources, often exhibit lower toxicity and can target multiple pathways involved in cancer progression and drug resistance. EVs can facilitate targeted drug delivery, modulate the immune response, and interact with the TME to sensitize cancer cells to treatment. However, the potential of PCs and engineered EVs in overcoming 5-FU resistance and reshaping the immunosuppressive TME in CRC remains underexplored. Addressing this gap is crucial for identifying innovative therapies with enhanced efficacy and reduced toxicities. This review explores the multifaceted mechanisms of 5-FU resistance in CRC and evaluates the synergistic effects of combining PCs with 5-FU to improve treatment efficacy while minimizing adverse effects. Additionally, it investigates engineered EVs in overcoming 5-FU resistance by serving as drug delivery vehicles and modulating the TME. By synthesizing the current knowledge and addressing research gaps, this review enhances the academic understanding of 5-FU resistance in CRC, highlighting the potential of interdisciplinary approaches involving PCs and EVs for revolutionizing CRC therapy. Further research and clinical validation are essential for translating these findings into improved patient outcomes. Full article

The emergence of the COVID-19 pandemic has led to the rapid and worldwide development and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aimed to explore the current knowledge on potential adverse endocrine effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pituitary, adrenal, diabetes, and gonadal events are also reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar searches were performed. Case reports, case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines are accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of the endocrine disorders linked to COVID-19 vaccines. Full article

The use of multimodal anaesthesia and analgesia is desirable as part of a complete analgesic plan. Analgesic strategies for perioperative pain treatment include combinations of drugs with different means of action to increase their efficacy and to reduce the required doses and adverse effects. Local anaesthetics prevent the transduction and transmission of painful stimuli through their action on neuronal cell membranes. They undergo minimal systemic absorption and are therefore ideal alternatives to drugs that could result in systemic toxicity. Numerous benefits have been recognised for the use of local anaesthesia, such as a decreased need for systemic analgesics and decreased hospitalisation periods. Local anaesthetics have been used in veterinary medicine in several ways. Anatomical landmarks can be used to identify the target nerves and the clinician can employ an electrical nerve stimulator or ultrasound guidance to perform a more accurate injection. Local anaesthetic techniques can implement other drugs, apart from or in combination with local anaesthetics, such as opioids, α₂−adrenergic agonists or vasoconstricting agents. This review article presents and discusses the most common techniques of local anaesthetic use in small animals, with the aim of providing the clinician with further and comprehensive information regarding the analgesic options during the perioperative period. Full article

Seismic intensity measures (IMs) can directly affect the seismic risk assessment and the response characteristics of underground structures, especially when considering the key variable of burial depth. This means that the optimal seismic IMs must be selected to match the underground structure under different buried depth conditions. In the field of seismic engineering design, peak ground acceleration (PGA) is widely recognized as the optimal IM, especially in the seismic design code for aboveground structures. However, for the seismic evaluation of underground structures, the applicability and effectiveness still face certain doubts and discussions. In addition, the adverse effects of earthquakes on tunnels in soft soil are particularly prominent. This study aims to determine the optimal IMs applicable to different burial depths for horseshoe-shaped tunnels in soft soil using a nonlinear dynamic time history analysis method, and based on this, establish the seismic fragility curves that can accurately predict the probability of tunnel damage. The nonlinear finite element analysis model for the soil–tunnel interaction system was established. The effects of different burial depths on damage to horseshoe-shaped tunnels in soft soil were systematically studied. By adopting the incremental dynamic analysis (IDA) method and assessing the correlation, efficiency, practicality, and proficiency of the potential IMs, the optimal IMs were determined. The analysis indicates that PGA emerges as the optimal IM for shallow tunnels, whereas peak ground velocity (PGV) stands as the optimal IM for medium-depth tunnels. Furthermore, for deep tunnels, velocity spectral intensity (VSI) emerges as the optimal IM. Finally, the seismic fragility curves for horseshoe-shaped tunnels in soft soil were built. The proposed fragility curves can provide a quantitative tool for evaluating seismic disaster risk, and are of great significance for improving the overall seismic resistance and disaster resilience of society. Full article

This study establishes a fetal cannabinoid syndrome model to evaluate the effects of high doses of dronabinol (synthetic THC) during pregnancy and lactation on behavioral and brain changes in male and female progeny and their susceptibility to alcohol consumption. Female C57BL/6J mice received dronabinol (10 mg/kg/12 h, p.o.) from gestational day 5 to postnatal day 21. On the weaning day, the offspring were separated by sex, and on postnatal day 60, behavioral and neurobiological changes were analyzed. Mice exposed to dronabinol exhibited increased anxiogenic and depressive-like behaviors and cognitive impairment. These behaviors were associated with neurodevelopment-related gene and protein expression changes, establishing, for the first time, an association among behavioral changes, cognitive impairment, and neurobiological alterations. Exposure to dronabinol during pregnancy and lactation disrupted the reward system, leading to increased motivation to consume alcohol in the offspring. All these modifications exhibited sex-dependent patterns. These findings reveal the pronounced adverse effects on fetal neurodevelopment resulting from cannabis use during pregnancy and lactation and strongly suggest the need to prevent mothers who use cannabis in this period from the severe and permanent side effects on behavior and brain development that may occur in their children. Full article

The progressive decline of the coal industry necessitates the development of effective treatment solutions for acid mine drainage (AMD), which is characterized by high acidity and elevated concentrations of heavy metals. This study proposes an innovative approach leveraging sulfate-reducing bacteria (SRB) acclimated to contaminated anaerobic environments. The research focused on elucidating the physiological characteristics and optimal growth conditions of SRB, particularly in relation to the pH level and temperature. The experimental findings reveal that the SRB exhibited a sulfate removal rate of 88.86% at an optimal temperature of 30 °C. Additionally, SRB gel particles were formulated using sodium alginate (SA) and carboxymethyl cellulose (CMC), and their performance was assessed under specific conditions (pH = 6, C/S = 1.5, T = 30 °C, CMC = 4.5%, BSNa = 0.4 mol/L, and cross-linking time = 9 h). Under these conditions, the SRB gel particles demonstrated an enhanced sulfate removal efficiency of 91.6%. Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) provided further insights into the stability and properties of the SRB gel spheres. The findings underscore the potential of SRB-based bioremediation as a sustainable and efficient method for AMD treatment, offering a novel and environmentally friendly solution to mitigating the adverse effects of environmental contamination. Full article

Fine particles (PM_2.5) have generally been reported as the major contributor to the adverse health effects of air pollution. Lebanon is characterized by a high density of transport, the production of electricity by generators, and a problem of uncontrolled incineration of household waste. For the purpose of this paper, the physico-chemical properties of fine (PM_2.5-0.3) and quasi-ultrafine (PM_0.3) particulate matter sampled in Southern Lebanon, were studied. Then, an evaluation and comparison of the toxicity of the different extracted fractions from PM (i.e., native PM_2.5-0.3 vs. organic extractable matter fraction (OEM_2.5-0.3), and non-extractable matter fraction (NEM_2.5-0.3)) was performed. Also, an examination of the toxicity of PM_0.3 was conducted indirectly through the evaluation of the OEM_0.3 harmfulness. The physico-chemical analysis showed that PM_0.3 was much more concentrated than PM_2.5-0.3 in organic compounds such as polycyclic aromatic hydrocarbons (PAHs) (28-fold) and their nitrated (N-PAHs, 14-fold) and oxygenated (O-PAHs, 10-fold) derivatives. Normal human bronchial epithelial cells (BEAS-2B) were exposed to PM_2.5-0.3, its derived fractions (i.e., OEM_2.5-0.3 and NEM_2.5-0.3), and OEM_0.3 before evaluating the global cytotoxicity, metabolic activation of organic compounds, genotoxicity, and inflammatory response. Different responses were observed depending on the considered fraction of particles. The global cytotoxicity showed a pronounced response related to ATP and LDH activities after exposure to the quasi-ultrafine organic extractable matter fraction (OEM_0.3). There was no significant induction of the AhR cell-signaling pathway by NEM_2.5-0.3. Despite the apparent difference in the kinetics of induction of the toxicological endpoints under study, OEM_0.3 provoked a higher overall cytotoxicity and genotoxicity than OEM_2.5-0.3 and total PM_2.5-0.3. Taken together, these results clearly showed that the finest particles are more damaging to BEAS-2B cells than PM_2.5-0.3 because they are richer in organic compounds, thereby inducing more remarkable toxic effects. Full article

Studies have shown that vehicle trajectory data are effective for calibrating microsimulation models. Light Detection and Ranging (LiDAR) technology offers high-resolution 3D data, allowing for detailed mapping of the surrounding environment, including road geometry, roadside infrastructures, and moving objects such as vehicles, cyclists, and pedestrians. Unlike other traditional methods of trajectory data collection, LiDAR’s high-speed data processing, fine angular resolution, high measurement accuracy, and high performance in adverse weather and low-light conditions make it well suited for applications requiring real-time response, such as autonomous vehicles. This research presents a comprehensive framework for integrating LiDAR sensor data into simulation models and their accurate calibration strategies for proactive safety analysis. Vehicle trajectory data were extracted from LiDAR point clouds collected at six urban signalized intersections in Lubbock, Texas, in the USA. Each study intersection was modeled with PTV VISSIM and calibrated to replicate the observed field scenarios. The Directed Brute Force method was used to calibrate two car-following and two lane-change parameters of the Wiedemann 1999 model in VISSIM, resulting in an average accuracy of 92.7%. Rear-end conflicts extracted from the calibrated models combined with a ten-year historical crash dataset were fitted into a Negative Binomial (NB) model to estimate the model’s parameters. In all the six intersections, rear-end conflict count is a statistically significant predictor (p-value < 0.05) of observed rear-end crash frequency. The outcome of this study provides a framework for the combined use of LiDAR-based vehicle trajectory data, microsimulation, and surrogate safety assessment tools to transportation professionals. This integration allows for more accurate and proactive safety evaluations, which are essential for designing safer transportation systems, effective traffic control strategies, and predicting future congestion problems. Full article