Investigating pedestrian-vehicle crashes on interstate highways: Applying random parameter binary logit model with heterogeneity in means.

In the U.S., the interstate highway system is categorized as a controlled-access or limited-access route, and it is unlawful for pedestrians to enter or cross this type of highway. However, pedestrian-vehicle crashes on the interstate highway system pose a distinctive safety concern. Most of these crashes involve 'unintended pedestrians', drivers who come out of their disabled vehicles, or due to the involvement in previous crashes on the interstate. Because these are not 'typical pedestrians', a separate investigation is required to better understand the pedestrian crash problem on interstate highways and identify the high-risk scenarios. This study explored 531 KABC (K = Fatal, A = Severe, B = Moderate, C = Complaint) pedestrian injury crashes on Louisiana interstate highways during the 2014-2018 period. Pedestrian injury severity was categorized into two levels: FS (fatal/severe) and IN (moderate/complaint). The random parameter binary logit with heterogeneity in means (RPBL-HM) model was utilized to address the unobserved heterogeneity (i.e., variations in the effect of crash contributing factors across the sample population) in the crash data. Some of the factors were found to increase the likelihood of pedestrian's FS injury in crashes on interstate highways, including pedestrian impairment, pedestrian action, weekend, driver aged 35-44 years, and spring season. The interaction of 'pedestrian impairment' and 'weekend' was found significant, suggesting that alcohol-involved pedestrians were more likely to be involved in FS crashes during weekends on the interstate. The obtained results can help the 'unintended pedestrians' about the crash scenarios on the interstate and reduce these unexpected incidents.

Investigating safety and cost-effectiveness of cable median barriers in Louisiana.

OBJECTIVES: Cable median barriers (CMBs) are installed on freeway medians to prevent cross-median crashes and reduce the severity of median-related crashes. Though CMBs are effective in preventing cross-median crashes, they are also known to increase the number of property damage-only (PDO) crashes. The higher frequency of PDO crashes could result in increased CMB maintenance and repair expenses. The aim of this study is to evaluate the safety impact and economic justification of CMBs in Louisiana. METHODS: Initially, a flowchart was developed using Louisiana crash data to identify targeted crashes, such as median-related and cross-median crashes. This was followed by a 3-year observational before-and-after crash analysis with an emphasis on head-on collisions and crashes involving large trucks. Using a 4-step improved prediction method, crash modification factors were then developed to quantitatively assess the impact of CMBs on crash outcomes, accounting for and adjusting to changes in the annual average daily traffic (AADT) and relevant crash frequencies before and after CMB implementation. Finally, an exhaustive benefit-cost analysis was conducted to determine the cost-effectiveness of CMBs. RESULTS: The results revealed that CMBs significantly reduced cross-median crashes of all severities. However, an increase in PDO crashes was observed in both total and median-related crashes. Large truck cross-median crashes and head-on collisions also decreased significantly after CMB implementation. Testing Level 4 (TL-4) CMBs were found to be more effective in preventing vehicles from crossing the median and in reducing crashes of higher severity levels. The benefit-cost ratios, calculated using economic crash unit costs for both total and targeted crashes, were greater than 1. Notably, the estimated benefit-cost ratios were considerably higher, demonstrating that CMBs are cost-effective countermeasures for enhancing traffic safety. CONCLUSION: This study contributes to the understanding of CMB performance from both traffic safety and economic perspectives. The findings may assist transportation agencies in making decisions regarding the management of CMB systems. Based on the comprehensive analysis of CMBs on Louisiana freeways, this project has revealed that CMBs are an effective and economically justified crash countermeasure. Thus, further implementation of CMBs is recommended until better alternatives are available.

Hyaluronic acid-modified liposomes Potentiated in-vivo anti-hepatocellular carcinoma of icaritin.

Introduction: Icaritin (ICT), a promising anti-hepatocellular carcinoma (HCC) prenylated flavonoid, is hindered from being applied due to its low water solubility and high lipophilicity in poorly differentiated HCC which is associated with upregulation of CD44 isoforms. Thus, hyaluronic acid (HA), a natural polysaccharide with high binding ability to CD44 receptors, was used to formulate a modified liposome as a novel targeted ICT-delivery system for HCC treatment. Methods: The ICT-Liposomes (Lip-ICT) with and without HA were prepared by a combined method of thin-film dispersion and post-insertion. The particle size, polydispersity (PDI), zeta potential, encapsulation efficacy (%EE), drug loading content (%DLC), and in vitro drug release profiles were investigated for physicochemical properties, whereas MTT assay was used to assess cytotoxic effects on HCC cells, HepG2, and Huh7 cells. Tumor bearing nude mice were used to evaluate the inhibitory effect of HA-Lip-ICT and Lip-ICT in vivo. Results: Lip-ICT and HA-Lip-ICT had an average particle size of 171.2 ± 1.2 nm and 208.0 ± 3.2 nm, with a zeta potential of -13.9 ± 0.83 and -24.8 ± 0.36, respectively. The PDI resulted from Lip-ICT and HA-Lip-ICT was 0.28 ± 0.02 and 0.26 ± 0.02, respectively. HA-Lip-ICT demonstrated higher in vitro drug release when pH was dropped from 7.4 to 5.5, The 12-h release rate of ICT from liposomes increased from 30% at pH7.4 to more than 60% at pH5.5. HA-Lip-ICT displayed higher toxicity than Lip-ICT in both HCC cells, especially Huh7with an IC50 of 34.15 ± 2.11 µM. The in vivo tissue distribution and anti-tumor experiments carried on tumor bearing nude mice indicated that HA-Lip- ICT exhibited higher tumor accumulation and achieved a tumor growth inhibition rate of 63.4%. Discussion: The nano-sized Lip-ICT was able to prolong the drug release time and showed long-term killing HCC cells ability. Following conjugation with HA, HA-Lip-ICT exhibited higher cytotoxicity, stronger tumor targeting, and tumor suppression abilities than Lip-ICT attributed to HA-CD44 ligand-receptor interaction, increasing the potential of ICT to treat HCC.

Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair.

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.