A Workable Solution for Reducing the Large Number of Vehicle and Pedestrian Accidents Occurring on a Yellow Light

Traffic intersections are incredibly dangerous for drivers and pedestrians. Statistics from both Canada and the U.S. show a high number of fatalities and serious injuries related to crashes at intersections. In Canada, during 2019, the National Collision Database shows that 28% of traffic fatalities and 42% of serious injuries occurred at intersections. Likewise, the U.S. National Highway Traffic Administration (NHTSA) found that about 40% of the estimated 5,811,000 accidents in the U.S. during the year studied were intersection-related crashes. In fact, a major survey by the car insurance industry found that nearly 85% of drivers could not identify the correct action to take when approaching a yellow traffic light at an intersection. One major reason for these accidents is the “yellow light dilemma,” the ambiguous situation where a driver should stop or proceed forward when unexpectedly faced with a yellow light. This situation is even further exacerbated by the tendency of aggressive drivers to inappropriately speed up on the yellow just to get through the traffic light. A survey of Canadian drivers conducted by the Traffic Injury Research Foundation found that 9% of drivers admitted to speeding up to get through a traffic light. Another reason for these accidents is the increased danger of making a left-hand turn on yellow. According to the National Highway Traffic Safety Association (NHTSA), left turns occur in approximately 22.2% of collisions—as opposed to just 1.2% for right turns. Moreover, a study by CNN found left turns are three times as likely to kill pedestrians than right turns. The reason left turns are so much more likely to cause an accident is because they take a driver against traffic and in the path of oncoming cars. Additionally, most of these left turns occur at the driver’s discretion—as opposed to the distressingly brief left-hand arrow at busy intersections. Drive Safe Now proposes a workable solution for reducing the number of accidents occurring during a yellow light at intersections. We believe this fairly simple solution will save lives, prevent injuries, reduce damage to public and private property, and decrease insurance costs.

Prevalence of Occupational Injury and Knowledge of Post-Exposure Prophylaxis Accessibility among Healthcare Workers in Mogadishu, Somalia

Introduction: Healthcare workers in Mogadishu, Somalia face significant occupational injury risks, particularly needle stick injuries, with 61.1% reporting incidents. This poses a serious threat to their health, leading to infections such as hepatitis B, hepatitis C, and HIV. Despite the high prevalence of injuries, awareness of Post-Exposure Prophylaxis (PEP) accessibility is relatively high, with 84.0% of respondents aware of it. However, there are gaps in knowledge and implementation, as evidenced by variations in availability of PEP. Improving workplace safety measures, providing comprehensive training on injury prevention and PEP protocols, and ensuring consistent availability of PEP in healthcare facilities are crucial steps to safeguard the well-being of healthcare workers in Mogadishu, Somalia. Methods: A cross-sectional study was conducted among hospital workers in Mogadishu, Somalia, focusing on professionals from various healthcare facilities. The study targeted nurses, doctors, laboratory personnel, and pharmacists. Purposive sampling was employed, resulting in a sample size of 383 calculated using Fisher’s sample size formula. Data were collected using coded questionnaires entered into Microsoft Excel 2019 and analyzed with SPSS software to generate frequencies and proportions, presented through frequency tables and pie figures. Results: The study in Mogadishu, Somalia, examined the prevalence of occupational injuries and knowledge of Post-Exposure Prophylaxis (PEP) accessibility among healthcare workers. Findings indicate a high prevalence of injuries, with 61.1% reporting incidents, predominantly needle stick injuries (60.6%). Despite the majority seeking prompt medical attention (72.0%), work-related illnesses affected 53.2% of respondents, notably work-related stress (59.5%). While most received training on injury and illness prevention (68.9%), gaps exist in PEP awareness, with 16.0% unaware of it. Nonetheless, 84.0% were aware, predominantly through health facilities (52.0%). Availability of PEP was reported by 71.3% in healthcare facilities, with variations in shift availability. The majority reported guidelines for PEP use (55.7%). Efforts are needed to bolster PEP awareness and ensure consistent availability in healthcare facilities to safeguard worker health. Conclusion: High prevalence of occupational injuries among healthcare workers, with needle stick injuries being the most common (60.6%). Despite this, 84.0% of respondents were aware of Post-Exposure Prophylaxis (PEP), primarily learning about it from health facilities (52.0%). While 71.3% reported the availability of PEP in their facility, 28.7% noted its unavailability. These results emphasize the need for improved education and accessibility of PEP to mitigate occupational injury risks.

Differences in pathological changes between two rat models of severe traumatic brain injury

The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relatively more stable,more reproducible,and shows obvious cerebral pathological changes at an earlier stage.Therefore,the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury,while the severe free weight drop model may be more apt for studies on diffuse axonal injury.All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University,China(approval No.IRB2012-028-02)in Febru ary 2012.

Outcomes of Early Primary Endoscopic Realignment and Delayed Reconstruction in the Management of Posterior Urethral Injury in Male

Background: Posterior urethral injury usually occurs in male patients with pelvic fractures. Posterior urethral injuries are associated with considerable morbidity including urinary incontinence, erectile dysfunction and urethral stricture. Objective: To compare the outcomes between early primary endoscopic realignment and delayed reconstruction in the management of male patients of posterior urethral injury. Methodology: This prospective study was conducted in the department of urology and department of casualty, Dhaka Medical College Hospital, Dhaka, Bangladesh from July 2015 to June 2017 among 50 male patients with posterior urethral injury. Fifty patients were randomly allocated into two groups;the group A consisted of 24 patients underwent early primary endoscopic realignment within 10 days after posterior urethral injury and the group B consisted of 26 patients underwent delayed reconstruction in form of anastomotic urethroplasty after 3 months. All patients were followed up at 3rd, 6th and 9th month after the procedure. Outcome variables were post-operative urethral stricture, urinary incontinence and erectile dysfunction. Data were analyzed and compared by statistical tests. Results: The mean (±SD) age of the study patients was almost similar between the groups (28.8 ± 8.4 vs. 27.4 ± 7.2 years, p = 0.486). In group A, 83.33% patients developed postoperative urethral stricture, none of them developed urinary incontinence and 20.83% developed erectile dysfunction;On the other hand, in group B, these rates were 38.46%, 23.07% and 38.46% respectively. Postoperative urethral stricture formation was significantly higher in Group A (p = 0.0012) but urinary incontinence and erectile dysfunction rates were significantly higher in Group B (p = 0.018 and p = 0.042 respectively). Conclusion: Early primary endoscopic realignment is better than delayed reconstruction in the management of male patients with posterior urethral injury. It provides less postoperative complications like urinary incontinence and erectile dysfunction, though postoperative urethral stricture formation is higher but amenable to be corrected endoscopically.

Establishing minimum clinically important difference values for the Patient-Reported Outcomes Measurement Information System Physical Function, hip disability and osteoarthritis outcome score for joint reconstruction, and knee injury and osteoarthritis out

AIM To establish minimum clinically important difference(MCID) for measurements in an orthopaedic patient population with joint disorders.METHODS Adult patients aged 18 years and older seeking care for joint conditions at an orthopaedic clinic took the Patient-Reported Outcomes Measurement Information System Physical Function(PROMIS~? PF) computerized adaptive test(CAT), hip disability and osteoarthritis outcome score for joint reconstruction(HOOS JR), and the knee injury and osteoarthritis outcome score for joint reconstruction(KOOS JR) from February 2014 to April 2017. MCIDs were calculated using anchorbased and distribution-based methods. Patient reports of meaningful change in function since their first clinic encounter were used as an anchor.RESULTS There were 2226 patients who participated with a mean age of 61.16(SD = 12.84) years, 41.6% male, and 89.7% Caucasian. Mean change ranged from 7.29 to 8.41 for the PROMIS~? PF CAT, from 14.81 to 19.68 for the HOOS JR, and from 14.51 to 18.85 for the KOOS JR. ROC cut-offs ranged from 1.97-8.18 for the PF CAT, 6.33-43.36 for the HOOS JR, and 2.21-8.16 for the KOOS JR. Distribution-based methods estimated MCID values ranging from 2.45 to 21.55 for the PROMIS~? PF CAT; from 3.90 to 43.61 for the HOOS JR, and from 3.98 to 40.67 for the KOOS JR. The median MCID value in the range was similar to the mean change score for each measure and was 7.9 for the PF CAT, 18.0 for the HOOS JR, and 15.1 for the KOOS JR.CONCLUSION This is the first comprehensive study providing a wide range of MCIDs for the PROMIS? PF, HOOS JR, and KOOS JR in orthopaedic patients with joint ailments.

Establishment and verification of a surgical prognostic model for cervical spinal cord injury without radiological abnormality

Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prognostic model of cervical spinal cord injury without radiological abnormality. This retrospective analysis included 43 patients with cervical spinal cord injury without radiological abnormality. Seven potential factors were assessed: age, sex, external force strength causing damage, duration of disease, degree of cervical spinal stenosis, Japanese Orthopaedic Association score, and physiological cervical curvature. A model was established using multiple binary logistic regression analysis. The model was evaluated by concordant profiling and the area under the receiver operating characteristic curve. Bootstrapping was used for internal validation. The prognostic model was as follows: logit(P) =-25.4545 + 21.2576 VALUE + 1.2160SCORE-3.4224 TIME, where VALUE refers to the Pavlov ratio indicating the extent of cervical spinal stenosis, SCORE refers to the Japanese Orthopaedic Association score(0–17) after the operation, and TIME refers to the disease duration(from injury to operation). The area under the receiver operating characteristic curve for all patients was 0.8941(95% confidence interval, 0.7930–0.9952). Three factors assessed in the predictive model were associated with patient outcomes: a great extent of cervical stenosis, a poor preoperative neurological status, and a long disease duration. These three factors could worsen patient outcomes. Moreover, the disease prognosis was considered good when logit(P) ≥-2.5105. Overall, the model displayed a certain clinical value. This study was approved by the Biomedical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University, China(approval number: 2018063) on May 8, 2018.

Bioinformatics analyses of differentially expressed genes associated with spinal cord injury:a microarray-based analysis in a mouse model

Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria

Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.

Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Expression signatures of long non-coding RNA and mRNA in human traumatic brain injury

Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

Upregulation of circ0000381 atienuates microglial/macrophage pyroptosis after spinal cord injury

Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied.In the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal cord.Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis marker.Therefore,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis.Indeed,knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis.Collectively,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury.Accordingly,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

Advantages of nanocarriers for basic research in the field of traumatic brain injury

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.