Pediatric all-terrain vehicle (ATV) related head injury rates and patterns: A 10-year nationwide analysis.

INTRODUCTION: The use of all-terrain vehicles (ATVs) carries significant risk of permanent injury and death, disproportionately affecting children. These injuries commonly affect the head and are especially severe among children as they are often unhelmeted and more likely than adults to experience rollover injuries. Many studies examining patients with ATV-related injuries are single-center cohort studies, with few focusing specifically on head injuries. In the present study, we aimed to characterize the annual incidence of ATV-related head injuries between 2012 and 2021, classify and compare head injury types, and identify descriptive characteristics of ATV-related head injury victims. METHODS: Using the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) database, we queried all head injuries associated with operating or riding an ATV in children under 18 years-old from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of incident, diagnoses, and sequelae were analyzed. We also collected the estimated number of ATV-related head injuries from all US EDs using the NEISS algorithm provided by the database. RESULTS: Using the NEISS algorithm we identified 67,957 (95% CI: 43,608 - 92,305) total pediatric ATV-related head injuries between 2012 and 2021. The annual incidence of ATV-related head injury was similar throughout this study period except for a 20% increase during the COVID-19 pandemic period of 2019-2021 (2019: 6382 injuries, 2020: 6757 injuries, 2021: 7600 injuries). A subset of 1890 cases from approximately 100 EDs were then analyzed. Unspecified closed head injuries were the prevailing type of injury (38%, 900/1890), followed by concussions (27%, 510/1890). More severe injuries included intracranial hemorrhages in 91 children (3.8%, 91/1890). Injuries of all types were predominantly seen in 14-17 year-old's (780/1890, 41%) and in males (64.1%, 1211/1890). In addition, ATV-associated injuries were significantly more common in those coded as white (58.0%, 1096/1890) than any other racial group. ATV-associated accidents among children younger than 9 more commonly occurred at the home compared to accidents involving children older than 9 (57% vs. 32%, p < 0.0001). CONCLUSION: ATV-related head injuries cause a significant annual burden among children, with growing incidence in recent years. Further research may wish to explore potential benefits of helmet use and supervision of younger children in possible prevention of these accidents and their associated economic and non-economic costs.

Forces required to operate controls on agricultural all-terrain vehicles: implications for youth.

All-terrain vehicle (ATV) crashes are among the leading causes of injury and death among youth in the agriculture industry. It is hypothesised that youth are involved in ATV-related incidents because they cannot effectively activate the vehicle's controls. This study evaluated potential discrepancies between the required activation forces of the controls of fifty-four utility ATVs and the strength of male-and-female youth of varying ages (6-20 years old) and strength percentiles (5th, 50th, and 95th). The activation forces of the ATVs' controls were measured experimentally, while the youth's corresponding strength was retrieved from the literature. The results of this study demonstrated a physical mismatch between the forces required to operate ATV controls and youth's strength. Turning the handlebar, pressing the footbrake, and pushing the ATV off are the most difficult tasks for ATV operation. These discrepancies compromise the youth's ability to ride ATVs, increasing their risk of crashes. Practitioner summary: Previous studies indicate that some youth engage in ATV incidents because they cannot activate the vehicle's controls. We measured the forces required to operate eight ATV controls and compared them with the youth's corresponding strength. Our results demonstrated physical mismatches between the forces required to operate ATV controls and the youth's strength.

Geriatric All-Terrain Vehicle Trauma: An Unhelmeted and Severely Injured Population.

BACKGROUND: All-terrain vehicle (ATV) use is widespread, however, little is known about injury patterns and outcomes in geriatric patients. We hypothesized that geriatric patients would have distinct and more severe injuries than non-geriatric adults after ATV trauma. METHODS: A retrospective cohort study was performed using the National Trauma Databank comparing non-geriatric (18-64) and geriatric adults (≥65) presenting after ATV trauma at Level 1 and 2 trauma centers from 2011 to 2015. Demographic, admission, and outcomes data were collected, including injury severity score (ISS), abbreviated injury scale (AIS) score, discharge disposition, and mortality. We performed univariate statistical tests between cohorts and multiple logistic regression models to assess for risk factors associated with severe injury (ISS>15) and mortality. RESULTS: 23,568 ATV trauma patients were identified, of whom 1,954 (8.3%) were geriatric. Geriatric patients had higher rates of severe injury(29.2 v 22.5%,p<0.0001), and thoracic (55.2 v 37.8%,p<0.0001) and spine (31.5 v 26.0%,p<0.0001) injuries, but lower rates of abdominal injuries (14.6 v 17.9%,p<0.001) as compared to non-geriatric adults. Geriatric patients had overall lower head injury rates (39.2 v 42.1%,p=0.01), but more severe head injuries (AIS>3) (36.2 vs 30.2%,p<0.001). Helmet use was significantly lower in geriatric patients (12.0 v 22.8%,p<0.0001). On multivariate analysis age increased the odds for both severe injury (OR 1.50, 95% CI 1.31-1.72, p<0.0001) and mortality (OR 5.07, 95% CI 3.42-7.50, p<0.0001). CONCLUSIONS: While severe injury and mortality after ATV trauma occurred in all adults, geriatric adults suffered distinct injury patterns and were at greater risk for severe injury and mortality.

Comparative analysis of off-road vehicle crashes in children: motorcycles versus quad bikes.

OBJECTIVE: To characterise and compare off-road motorcycle and quad bike crashes in children in New South Wales (NSW), Australia. METHODS: A retrospective, cross-sectional study was performed of children aged 0-16 years, admitted to hospitals in NSW, from 2001 to 2018 following an injury sustained in an off-road motorcycle or quad bike crash, using linked hospital admissions, mortality and census data.Motorcycle and quad bike injuries were compared regarding: demographics; incidence; body region injured and type of injury; injury severity based on the survival risk ratio; length of stay and mortality. RESULTS: There were 6624 crashes resulting in hospitalisation; 5156 involving motorcycles (77.8%) and 1468 involving quad bikes (22.2%). There were 10 fatalities (6 from motorcycles and 4 from quad bikes). The rates of injury declined over the study period for motorcycles, but not for quad bikes.Motorcycle riders were more likely than quad bike riders to have lower limb injuries (OR 1.49, p<0.001) but less likely to have head/neck (OR 0.616, p<0.001), abdominal (OR 0.778, p=0.007) and thoracic (OR 0.745, p=0.003) injuries. Quad bike crashes resulted in higher injury severity (mean International Classification Injury Severity Score 0.975 vs 0.977, p=0.03) and longer hospital stay (mean 2.42 days vs 2.09 days, p=0.01). CONCLUSIONS: There are significant differences between quad bike and motorcycle crashes in injury type and affected body region. While quad bike injuries in children were more severe, there were almost four times more hospitalisations from motorcycles overall. The overall larger burden of motorcycle crashes suggests a greater focus of injury prevention countermeasures for two-wheeled riders is needed.

Anthocyanin Fruit encodes an R2R3-MYB transcription factor, SlAN2-like, activating the transcription of SlMYBATV to fine-tune anthocyanin content in tomato fruit.

Anthocyanin fruit (Aft) and atroviolacea (atv) were characterized in wild tomato and can enhance anthocyanin content in tomato fruit. However, the gene underlying the Aft locus and the mechanism by which Aft and atv act remain largely unknown. In this study, the Aft locus was fine-mapped to an approximately 145-kb interval on chromosome 10, excluding SlAN2 (Solyc10g086250), SlANT1 (Solyc10g086260) and SlANT1-like (Solyc10g086270), which have previously been suggested as candidates. Thus, the R2R3-MYB transcription factor SlAN2-like (Solyc10g086290) was considered the best candidate gene for Aft. The CRISPR/Cas9-mediated SlAN2-like mutants show a much lower accumulation of anthocyanins associated with the downregulation of multiple anthocyanin-related genes compared to the wild-type tomato, indicating that SlAN2-like is responsible for the Aft phenotype. The repressive function of SlMYBATV also was confirmed through the CRISPR/Cas9 approach. A yeast-two-hybrid assay revealed that SlMYBATV interacts with the bHLH protein SlJAF13. Furthermore, yeast-one-hybrid and dual-luciferase transient expression assays showed that Aft directly binds to the SlMYBATV promoter and activates its expression. The results herein provide candidate genes to enhance anthocyanin content in tomato fruit. This research also provides insight into a mechanism involving the Aft-SlMYBATV pathway that fine-tunes anthocyanin accumulation in tomato fruit.

Therapeutic Effects of Iron Chelation in Atorvastatin-Induced Intracranial Hemorrhage of Zebrafish Larvae.

OBJECTIVE: Intracranial hemorrhage (ICH) catastrophically damages the cerebral vasculature, and severely compromises blood-brain barrier (BBB) function. The prognosis of ICH is poor due to the drastic and rapid progression of its pathology, and the lack of effective treatments presents a significant unmet clinical need. The present paper provides several evidences about the relationship between ICH bleeding status and mortality and the potential therapeutic effects of an iron chelator for ICH. METHODS: Zebrafish are a highly transparent animal model, allowing live imaging of the complex cerebral vasculature. Thus, to further elucidate ATV-induced ICH, we investigated the concentration- and time-dependent phenotypes of ATV-induced ICH with zebrafish larvae. RESULTS: The effects of ATV on mortality and ICH incidence in zebrafish larvae were concentration-dependent. Further, ATV treatment decreased vascular density of the hindbrain in a concentration-dependent manner, and hematoma volume was inversely correlated with ATV concentration. The number of cranial TUNEL-positive apoptotic cells was markedly increased 3 days post-fertilization. Importantly, the iron chelator deferasirox (DFR) decreased the incidence of ATV-induced ICH in zebrafish larvae. CONCLUSION: These findings provided insight into the pathology and regulatory mechanism of ATV-induced ICH, and demonstrated the therapeutic effects of iron chelators.

Characterization of all-terrain vehicle-related chest injury patterns in children.

PURPOSE: To evaluate chest injury patterns in pediatric patients involved in all-terrain vehicle (ATV) accidents. METHODS: Retrospective review of patients 0-18 years old admitted to a level I trauma institute following an ATV-related incident from 2004 to 2013 was performed. Chest injury type, accident mechanism, driver/passenger status, and demographic and clinical data were compared between patients with and without chest injury. RESULTS: Chest injury was present in 102 (22%) of total 455 patients. The most common chest injuries were pulmonary contusion (61%), pneumothorax (45%), and rib fracture (34%). There were no cardiac, esophageal, or tracheobronchial injuries. Pulmonary lacerations, hemothoraces, and scapular fractures were predominantly not detected on radiography and recognized on CT only (86-92%). Patients with chest injury had longer median hospital stays (3 days vs 2 days, p = 0.0054). There was no significant difference in admission to intensive care after controlling for injury severity scores in patients with chest injury compared to those without (17 vs 9). Eight patients with chest injury died (8%) compared to 2 patients without chest injury (0.6%) (p = 0.0002). CONCLUSIONS: Chest injuries are common in children following ATV accidents and may be a marker of more severe trauma. Increased public awareness of these potentially devastating injuries and continuing safety efforts are needed.

A Generic Multi-Layer Architecture Based on ROS-JADE Integration for Autonomous Transport Vehicles.

The design and operation of manufacturing systems is evolving to adapt to different challenges. One of the most important is the reconfiguration of the manufacturing process in response to context changes (e.g., faulty equipment or urgent orders, among others). In this sense, the Autonomous Transport Vehicle (ATV) plays a key role in building more flexible and decentralized manufacturing systems. Nowadays, robotic frameworks (RFs) are used for developing robotic systems such as ATVs, but they focus on the control of the robotic system itself. However, social abilities are required for performing intelligent interaction (peer-to-peer negotiation and decision-making) among the different and heterogeneous Cyber Physical Production Systems (such as machines, transport systems and other equipment present in the factory) to achieve manufacturing reconfiguration. This work contributes a generic multi-layer architecture that integrates a RF with a Multi-Agent System (MAS) to provide social abilities to ATVs. This architecture has been implemented on ROS and JADE, the most widespread RF and MAS framework, respectively. We believe this to be the first work that addresses the intelligent interaction of transportation systems for flexible manufacturing environments in a holistic form.

The characteristics of all-terrain vehicle (ATV)-related deaths: A forensic autopsy data-based study.

Using forensic autopsy-based data from a regional medical examiner office in the midwestern U.S. with a mixed small urban-rural population, we describe the characteristics of all-terrain vehicle (ATV)-related deaths occurring between 2000 and 2018. During this period, there were 25 ATV-related deaths. There was a strong male predominance with 22 male and 3 female decedents. The average age at death was 35 years, with a range from 10 to 82 years, and a bimodal age distribution with one peak at 10-19 years old, and a second peak at 60-69 years old. The most common cause of death was blunt trauma (n = 22), with the remainder being torso compression (n = 1), drowning (n = 1) and hypothermia (n = 1). Of the 22 blunt trauma deaths, 15 were due to head trauma. The most common mechanism of accident was roll-over (n = 11), followed by striking a stationary object (n = 6). Of the stationary objects struck, the most common was cable wire fencing accounting for 3 of the 6. A survival period following discovery of the body was present in 11 of the 25 deaths. Postmortem toxicology was positive for ethanol in 7 deaths and tramadol in 1 death.

Atazanavir-Associated Crystalline Nephropathy.

Crystalline nephropathy can occur following treatment with multiple therapeutic agents. We describe a human immunodeficiency virus (HIV)-infected patient treated for 2 years with combination antiretroviral therapy including atazanavir (ATV). Kidney biopsy revealed a crystalline nephropathy associated with diffuse chronic and granulomatous interstitial inflammation. Following the biopsy, treatment with ATV was discontinued and kidney function returned to pretreatment baseline levels. ATV, which has a well-established association with nephrolithiasis, is a rare but important cause of crystalline nephropathy. Recognition of this association and prompt withdrawal of the offending agent are critical to optimize outcomes.

Limitations in the field of vision of young operators of utility all-terrain vehicles.

PROBLEM: All-Terrain Vehicles (ATVs) cause a distressing number of fatalities and injuries among farm youth in the United States. The number of severe injuries caused by ATV crashes on farms, which stood at 25 children in 2019, is expected to rise due to increased ATV sales during the COVID-19 pandemic. Existing research into children's injuries has explored physical capabilities like anthropometry, strength, and visual acuity. Yet, studies assessing youths' physical ability to operate ATVs remain limited. This study tests the hypothesis that diminished vision field in young ATV operators raises crash risks. METHODS: This study used SAMMIECAD digital human modeling system to simulate and compare the field of vision of youth and adult ATV operators. The simulations incorporated 3-D mockups of ATVs, humans, sprayer tanks, windshields, and obstacles. Ten utility ATVs and children of both genders across nine ages (8-16) and three height percentiles (5th, 50th, 95th) were evaluated. RESULTS: Simulations showed that young ATV operators generally have a more restricted field of vision than adults, particularly those aged 6-11 years. DISCUSSION: Visual limitations hinder riders' ability to see ATV controls, potentially leading to vehicle control loss. Moreover, they impair environmental perception during riding, compromising youths' ATV operation abilities and increasing crash risks. PRACTICAL APPLICATIONS: These findings offer crucial data in support of modifying ATV safety guidelines. Additionally, they can guide youth occupational health professionals in preventing ATV-related incidents in agricultural settings.

PET imaging of microglia in Alzheimer's disease using copper-64 labeled TREM2 antibodies.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays an essential role in microglia activation and is being investigated as a potential therapeutic target for modulation of microglia in several neurological diseases. In this study, we present the development and preclinical evaluation of 64Cu-labeled antibody-based PET radiotracers as tools for non-invasive assessment of TREM2 expression. Furthermore, we tested the potential of an antibody transport vehicle (ATV) that binds human transferrin receptor to facilitate transcytosis of TREM2 antibody-based radiotracers to the CNS and improve target engagement. Methods: A TREM2 antibody with an engineered transport vehicle (ATV:4D9) and without (4D9) were covalently modified with pNCS-benzyl-NODAGA and labeled with copper-64. Potency, stability, and specificity were assessed in vitro followed by in vivo PET imaging at the early 2 h, intermediate 20 h, and late imaging time points 40 h post-injection using a human transferrin receptor (hTfR) expressing model for amyloidogenesis (5xFAD;TfRmu/hu) or wild-type mice (WT;TfRmu/hu), and hTfR negative controls. Organs of interest were isolated to determine biodistribution by ex vivo autoradiography. Cell sorting after in vivo tracer injection was used to demonstrate cellular specificity for microglia and to validate TREM2 PET results in an independent mouse model for amyloidogenesis (AppSAA;TfRmu/hu). For translation to human imaging, a human TREM2 antibody (14D3) was radiolabeled and used for in vitro autoradiography on human brain sections. Results: The 64Cu-labeled antibodies were obtained in high radiochemical purity (RCP), radiochemical yield (RCY), and specific activity. Antibody modification did not impact TREM2 binding. ATV:4D9 binding proved to be specific, and the tracer stability was maintained over 48 h. The uptake of [64Cu]Cu-NODAGA-ATV:4D9 in the brains of hTfR expressing mice was up to 4.6-fold higher than [64Cu]Cu-NODAGA-4D9 in mice without hTfR. TREM2 PET revealed elevated uptake in the cortex of 5xFAD mice compared to wild-type, which was validated by autoradiography. PET-to-biodistribution correlation revealed that elevated radiotracer uptake in brains of 5xFAD;TfRmu/hu mice was driven by microglia-rich cortical and hippocampal brain regions. Radiolabeled ATV:4D9 was selectively enriched in microglia and cellular uptake explained PET signal enhancement in AppSAA;TfRmu/hu mice. Human autoradiography showed elevated TREM2 tracer binding in the cortex of patients with Alzheimer's disease. Conclusion: [64Cu]Cu-NODAGA-ATV:4D9 has potential for non-invasive assessment of TREM2 as a surrogate marker for microglia activation in vivo. ATV engineering for hTfR binding and transcytosis overcomes the blood-brain barrier restriction for antibody-based PET radiotracers. TREM2 PET might be a versatile tool for many applications beyond Alzheimer's disease, such as glioma and chronic inflammatory diseases.

Antiretroviral action of Rosemary oil-based atazanavir formulation and the role of self-nanoemulsifying drug delivery system in the management of HIV-1 infection.

Atazanavir or ATV is an FDA-approved, HIV-1 protease inhibitor that belongs to the azapeptide group. Over time, it has been observed that ATV can cause multiple adverse side effects in the form of liver diseases including elevations in serum aminotransferase, indirect hyper-bilirubinemia, and idiosyncratic acute liver injury aggravating the underlying chronic viral hepatitis. Hence, there is an incessant need to explore the safe and efficacious method of delivering ATV in a controlled manner that may reduce the proportion of its idiosyncratic reactions in patients who are on antiretroviral therapy for years. In this study, we assessed ATV formulation along with Rosemary oil to enhance the anti-HIV-1 activity and its controlled delivery through self-nanoemulsifying drug delivery system or SNEDDS to enhance its oral bioavailability. While the designing, development, and characterization of ATV-SNEDDS were addressed through various evaluation parameters and pharmacokinetic-based studies, in vitro cell-based experiments assured the safety and efficacy of the designed ATV formulation. The study discovered the potential of ATV-SNEDDS to inhibit HIV-1 infection at a lower concentration as compared to its pure counterpart. Simultaneously, we could also demonstrate the ATV and Rosemary oil providing leads for designing and developing such formulations for the management of HIV-1 infections with the alleviation in the risk of adverse reactions.

CETP-derived Peptide Seq-1, the Key Component of HB-ATV-8 Vaccine Prevents Stress Responses, and Promotes Downregulation of Pro-Fibrotic Genes in Hepatocytes and Stellate Cells.

BACKGROUND: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis. METHODS: The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-ß, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied. AIM: To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC. RESULTS AND CONCLUSION: Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-ß genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.

Role of P-glycoprotein in the efflux of raltegravir from human intestinal cells and CD4+ T-cells as an interaction target for anti-HIV agents.

Cellular efflux and uptake transports of several anti-HIV agents are mediated by plasma membrane-localized solute transporters. However, transporters involved in raltegravir disposition have not been fully characterized. Here, we performed in vitro studies to identify transporters mediating transcellular transport of raltegravir. Transepithelial raltegravir transport was examined using porcine kidney epithelial cell line (LLC-PK1) and LLC-PK1 cells stably transfected with P-glycoprotein (also known as Multiple drug resistance 1) (L-MDR1). Transepithelial transport of raltegravir in Caco-2 cell monolayers, and intracellular accumulation of raltegravir in the MT-2 and MT-4 (CD4+ T-) cells were measured in the presence or absence of anti-HIV agents. The uptake of raltegravir was investigated in HEK-293 cells expressing each of several solute carrier family transporters. The apical-to-basal raltegravir transport was significantly decreased in L-MDR1 as compared to that in LLC-PK1 monolayers. In HEK-293 cells expressing breast cancer resistance protein (BCRP), raltegravir accumulation was lower than that in the mock-transfected cells. In Caco-2 cells, protease inhibitors including nelfinavir, ritonavir and lopinavir enhanced the apical-to-basal transport of raltegravir. By contrast, reverse transcriptase inhibitors such as zidovudine, efavirenz, and nevirapine, had no effect on raltegravir transport. The cellular accumulation of raltegravir in MT-2 cells, which express P-glycoprotein, was significantly increased in the presence of protease inhibitors. By contrast, protease inhibitors only marginally increased the accumulation of raltegravir in MT-4 cells, in which P-glycoprotein is not expressed. The present findings suggest that raltegravir is a substrate of both P-glycoprotein and BCRP. Protease inhibitors increase the absorptive transport of raltegravir in Caco-2 cells, and the cellular accumulation in T-cells, at least in part, by P-glycoprotein-mediated interaction.

Accumulation of anthocyanins in tomato skin extends shelf life.

Shelf life is one of the most important traits for the tomato (Solanum lycopersicum) industry. Two key factors, post-harvest over-ripening and susceptibility to post-harvest pathogen infection, determine tomato shelf life. Anthocyanins accumulate in the skin of Aft/Aft atv/atv tomatoes, the result of introgressing alleles affecting anthocyanin biosynthesis in fruit from two wild relatives of tomato, which results in extended fruit shelf life. Compared with ordinary, anthocyanin-less tomatoes, the fruits of Aft/Aft atv/atv keep longer during storage and are less susceptible to Botrytis cinerea, a major tomato pathogen, post-harvest. Using genetically modified tomatoes over-producing anthocyanins, we confirmed that skin-specific accumulation of anthocyanins in tomato is sufficient to reduce the susceptibility of fruit to Botrytis cinerea. Our data indicate that accumulation of anthocyanins in tomato fruit, achieved either by traditional breeding or genetic engineering can be an effective way to extend tomato shelf life.

Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections.

Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, up to a five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. FROM THE CLINICAL EDITOR: This team of authors describes a novel method for macrophage folate receptor-targeted antiretroviral therapy. Atazanvir entry, retention, and antiretroviral activities were superior using the presented method, and so was its biodistribution, enabling a more efficient way to address human immunodeficiency virus infections, with a hoped for clinical application in the near future.

Changes in pediatric injuries sustained while engaged in activities where helmet usage is recommended during the COVID-19 pandemic.

BACKGROUND: Unintentional injuries, including traumatic brain injuries (TBI), are the leading cause of pediatric morbidity and mortality in the USA. Helmet usage can reduce TBI incidence and severity; however, the epidemiology of pediatric TBI and helmet use is ever evolving. With lifestyle changes potentially accelerated by the pandemic, we predicted a decrease in helmet utilization with an associated increase in TBI during the pandemic compared to the pre-pandemic period. RESULTS: There were 1093 patients that presented with AWHUR injuries from 2018 to 2020 with an annual increase from 263 patients in 2018 up to 492 in 2020. The most frequently implicated mechanisms included bicycles (35.9%), ATVs (20.3%), skateboards (11.6%), scooters (8.3%), and dirt bikes (7.4%). Unhelmeted patients increased from 111 (58.7%) in 2018 to 258 (64.8%) in 2020. There was not a significant difference in the proportion of injuries that were unhelmeted from 38.9% in 2018-2019 to 35.2% in 2020 (p = 0.30), as well as the proportion of head injuries from 2018 to 2019 (24.3%) to 2020 (29.3%) (p = 0.07). A significant increase was seen in neurosurgical consultation from 17 (6.5%) in 2018 to 87 (17.7%) in 2020 (p = 0.02). Notably, there was an increase in the percentage of publicly insured patients presenting with injuries from AWHUR during 2020 (p < 0.001); this group also had suboptimal helmet usage. CONCLUSION: This study found an increase in patients presenting with injuries sustained while engaged in AWHUR in relation to the COVID-19 pandemic. Concerningly, there was a trend toward decreased helmet utilization and increased injury severity markers. Further analysis is needed into the communities impacted the most by AWHUR injuries.

Ability of youth operators to reach agricultural all-terrain vehicles controls.

PROBLEM: Utility All-Terrain Vehicles (ATVs) are one major cause of youth injuries and fatalities on farms. Utility ATVs have heavy weights and fast speeds that require complex maneuvering. Youth's physical capabilities may not be sufficient to perform those complex maneuvers correctly. Therefore, it is hypothesized that most youth engage in ATV-related incidents because they ride vehicles unfit for them. There is a need to assess ATV-youth fit based on youth anthropometry. METHOD: This study focused on evaluating potential inconsistencies between the operational requirements of utility ATVs and the anthropometric measures of youth through virtual simulations. Virtual simulations were performed to assess 11 youth-ATV fit guidelines proposed by several ATV safety advocacy organizations (National 4-H council, CPSC, IPCH, and FReSH). In total, 17 utility ATVs along with male-and-female-youth of nine ages (8 to 16 years old) and three height percentiles (5th, 50th, and 95th) were evaluated. RESULTS: The results demonstrated a physical mismatch between ATVs' operational requirements and youth's anthropometry. For example, male-youth aged 16 of the 95th height percentile failed to pass at least 1 out of the 11 fit guidelines for 35 % of all vehicles evaluated. The results were even more concerning for females. Female youth 10 years old and younger (from all height percentiles) failed to pass at least one fit guideline for all ATVs evaluated. DISCUSSION: Youth are not recommended to ride utility ATVs. PRACTICAL APPLICATIONS: This study provides quantitative and systematic evidence to modify current ATV safety guidelines. Furthermore, youth occupational health professionals could use the present findings to prevent ATV-related incidents in agricultural settings.

A Systematic Review of Youth and All-Terrain Vehicles Safety in Agriculture.

All-terrain vehicle (ATV) incidents are one of the leading causes of injuries and fatalities among youth in the agricultural industry. It has been hypothesized that many youth-related ATV incidents occur because children ride ATVs that do not fit their capabilities and are not following basic safe riding practices. In addition, various ATV safety guidelines regarding youth (e.g., CPSC, ANSI/SVIA, ASI) are inconsistent and may not align with state or local laws. To the best of our knowledge, no comprehensive studies have compared the physical and mental requirements for riding ATVs and the youth's capabilities to ride ATVs safely. Consequently, there are no scientific-based recommendations for age limitation, physical and mental capabilities, and safety requirements for youth to ride ATVs safely. Thus, there is a need to review the available sources related to youth safety and ATVs in the agricultural industry, identify the research voids, and recommend modifications to current ATV guidelines. This study conducted a systematic review of available ATV-related studies, standards, guidelines, and laws to establish better-informed minimum age, physical and mental capabilities, and safety requirements for youths to ride ATVs on the farm.