Source-Dependent Quality Variation in Shoulder Dislocation Videos on YouTube.

Purpose: To assess the quality of YouTube videos for patient education on shoulder dislocation. Methods: A standard YouTube search was performed in March 2023 using the terms "shoulder dislocation," "dislocated shoulder," and "glenohumeral joint dislocation" to identify eligible videos. Multiple scoring systems, including DISCERN (a validated tool for analyzing the quality of health information in consumer-targeted videos), Journal of the American Medical Association (JAMA) Benchmark Criteria, and the Global Quality Score (GQS) were used to evaluate the videos. Video quality scores from various sources were compared using the Kruskal-Wallis test for initial analysis, followed by Dunn's post-hoc test with Bonferroni correction, and the strength of relationship between variables was assessed using Spearman's rank correlation coefficient. Results: A total of 162 eligible videos were identified. The mean video duration was 11.38 ± 3.01 minutes, the median number of views was 653. Median number of days since upload was 1,972, the median view rate was 0.343, and median number of likes was 66.12. Based on the DISCERN classification, a substantial proportion of videos were classified as insufficient quality, with 19.4% as "very insufficient" and 42.1% as "insufficient"; 24.1% were classified as "average" quality, whereas only 13.1% were classified as "good" and 1.2% were "excellent." Videos from academic and professional sources showed a significant positive correlation with DISCERN scores (rho: +0.784, P < .001) and greater scores on all 4 scoring systems compared to health information websites. Conclusions: This study reveals that the majority of YouTube videos on shoulder dislocation lack sufficient quality for patient education, with content quality significantly influenced by the source. Clinical Relevance: Examining the accuracy of information that patients encounter on YouTube is essential for health care providers to direct individuals toward more reliable sources of information.

Steady-state, therapeutic, and helminth-induced IL-4 compromise protective CD8 T cell bystander activation.

Memory CD8 T cells (Tmem) can be activated into innate-like killers by cytokines like IL-12, IL-15, and/or IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are not fully resolved. We found strain-intrinsic deficiencies in bystander activation using specific pathogen-free mice, whereby basal IL-4 signals antagonize IL-18 sensing. We show that therapeutic and helminth-induced IL-4 impairs protective bystander-mediated responses against pathogens. However, this IL-4/IL-18 axis does not completely abolish bystander activation but rather tunes the expression of direct versus indirect mediators of cytotoxicity (granzymes and interferon-γ, respectively). We show that antigen-experience overrides strain-specific deficiencies in bystander activation, leading to uniform IL-18 receptor expression and enhanced capacity for bystander activation/cytotoxicity. Our data highlight that bystander activation is not a binary process but tuned/deregulated by other cytokines that are elevated by contemporaneous infections. Further, our findings underscore the importance of antigen-experienced Tmem to dissect the contributions of bystander Tmem in health and disease.

Very low levels of ABCA7 in the cerebrum and Alzheimer's disease onset between the ages of 60 and 80 independently of APOE.

This cross-sectional study addressed the ABCA7-Alzheimer's disease (AD) association. ABCA7 protein levels were quantified in 3 cerebral regions of brain donors with Braak neurofibrillary tangle (NFT) stages 0-V. Ordinal regression models were implemented to estimate the effect of ABCA7 on stopping in an earlier Braak NFT stage versus progressing to the later stages in 2 prespecified age segments. In the final model, high ABCA7 levels in the parietal cortex increased the odds of remaining cognitively healthy (ie, in stages 0/I) versus experiencing AD onset (ie, progressing to stages II-V) in the 61-80 age segment (OR = 2.87, adj 95% CI = 1.41-7.86, adj P = .007, n = 109), after controlling for APOE and other covariates. No ABCA7-AD association was found in the 81-98 age segment (n = 113). Parietal ABCA7 levels in 61-80-year-old with stages II-V were very low, even significantly lower than in 81-98-year-old with stages II-V. ABCA7 levels in the prefrontal cortex and hippocampus predicted AD onset in the 61-80 age segment after adjustment for APOE. ABCA7 levels were also the lowest in 61-80-year-old with frequent neuritic plaques. Thus, very low ABCA7 levels in the cerebrum are associated with AD onset in the 7th-8th decade of life.

Collaboration between IL-7 and IL-15 enables adaptation of tissue-resident and circulating memory CD8+ T cells.

Interleukin-7 (IL-7) is considered a critical regulator of memory CD8+ T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (TRM) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that Il7ra loss had only a modest effect on persistence of circulating memory and TRM subsets and that IL-7Rα was primarily required for normal basal proliferation. Loss of IL-15 signaling imposed heightened IL-7Rα dependence on memory CD8+ T cells, including TRM populations previously described as IL-15-independent. In the absence of IL-15 signaling, IL-7Rα was upregulated, and loss of IL-7Rα signaling reduced proliferation in response to IL-15, suggesting cross-regulation in memory CD8+ T cells. Thus, across subsets and tissues, IL-7 and IL-15 act in concert to support memory CD8+ T cells, conferring resilience to altered availability of either cytokine.

Lack of Consensus on the Management of Medial Collateral Ligament Tears in the Setting of Concomitant Anterior Cruciate Ligament Injury: A Critical Analysis.

¼ There is no clear agreement on the optimal timing or superior type of fixation for medial collateral ligament (MCL) tears in the setting of anterior cruciate ligament (ACL) injury.¼ Anatomic healing of medial knee structures is critical to maintain native knee kinematics, supported by biomechanical studies that demonstrate increased graft laxity and residual valgus rotational instability after ACL reconstruction (ACLR) alone in the setting of concomitant ACL/MCL injury.¼ Historically, most surgeons have favored treating acute combined ACL/MCL tears conservatively with MCL rehabilitation, followed by stress radiographs at 6 weeks after injury to assess for persistent valgus laxity before performing delayed ACLR to allow for full knee range of motion, and reduce the risk of postoperative stiffness and arthrofibrosis.¼ However, with the advancement of early mobilization and aggressive physical therapy protocols, acute surgical management of MCL tears in the setting of ACL injury can have benefits of avoiding residual laxity and further intra-articular damage, as well as earlier return to sport.¼ Residual valgus laxity from incomplete MCL healing at the time of ACLR should be addressed surgically, as this can lead to an increased risk of ACLR graft failure.¼ The treatment of combined ACL/MCL injuries requires an individualized approach, including athlete-specific factors such as level and position of play, timing of injury related to in-season play, contact vs. noncontact sport, and anticipated longevity, as well as consideration of the tear pattern, acuity of injury, tissue quality, and surgeon familiarity with the available techniques.

Voltinism of a solitary bee was influenced by temperature but not provision size.

Changes in the timing and duration of life cycles are distinctive fingerprints of environmental change. Yet, the biotic and abiotic cues underpinning phenology and voltinism, i.e., number of generations per year, are poorly understood. Here, I experimentally test how temperature and provision size influence voltinism and survival to emergence in a solitary bee Colletes validus, and how temperature influences voltinism in the brood parasite Tricrania sanguinipennis. Within the same population, univoltine individuals emerge after 1 year (1-year form), whereas semivoltine individuals enter prolonged dormancy and emerge after 2 years (2-year form). I reared field-collected bees under 2 × 2 factorial experiments with cool (18.5 °C ± 0.5 °C) vs. warm (24 °C ± 0.5 °C) temperature treatments (bees and beetles) and no supplement vs. supplemental food treatments (+ 20% ± 5% pollen provision by mass); beetles were reared under temperature treatments only. Cool temperatures consistently increased the proportion of 2-year bees regardless of provision size, a finding that was consistent with three years of field observations. There was a demographic cost to prolonged dormancy in that both 1- and 2-year bees survived to emergence as adults, but survival of 2-year bees was approximately 50% lower than 1-year bees. Two-year beetles were produced under cooler temperatures, but unlike bees, beetles had nearly perfect survival to emergence in all treatments. This experiment advances our mechanistic understanding of the environmental drivers of voltinism in diverse insect taxa and underscores the importance of considering cryptic life stages when interpreting responses to environmental change.

Porous Se@SiO2 nanocomposites play a potential inhibition role in hyperoxaluria associated kidney stone by exerting antioxidant effects.

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

Evolving Improved Sampling Protocols for Dose-Response Modelling Using Genetic Algorithms with a Profile-Likelihood Metric.

Practical limitations of quality and quantity of data can limit the precision of parameter identification in mathematical models. Model-based experimental design approaches have been developed to minimise parameter uncertainty, but the majority of these approaches have relied on first-order approximations of model sensitivity at a local point in parameter space. Practical identifiability approaches such as profile-likelihood have shown potential for quantifying parameter uncertainty beyond linear approximations. This research presents a genetic algorithm approach to optimise sample timing across various parameterisations of a demonstrative PK-PD model with the goal of aiding experimental design. The optimisation relies on a chosen metric of parameter uncertainty that is based on the profile-likelihood method. Additionally, the approach considers cases where multiple parameter scenarios may require simultaneous optimisation. The genetic algorithm approach was able to locate near-optimal sampling protocols for a wide range of sample number (n = 3-20), and it reduced the parameter variance metric by 33-37% on average. The profile-likelihood metric also correlated well with an existing Monte Carlo-based metric (with a worst-case r > 0.89), while reducing computational cost by an order of magnitude. The combination of the new profile-likelihood metric and the genetic algorithm demonstrate the feasibility of considering the nonlinear nature of models in optimal experimental design at a reasonable computational cost. The outputs of such a process could allow for experimenters to either improve parameter certainty given a fixed number of samples, or reduce sample quantity while retaining the same level of parameter certainty.

Meniscal extrusion consensus statement: A collaborative survey within the Meniscus International Network (MenIN) Study Group.

PURPOSE: The purpose of the present study was to perform a survey administered to members of the Meniscus International Network (MenIN) Study Group, seeking to delineate the most contentious aspects of meniscal extrusion classification and provide a foundation for new, more comprehensive definitions and treatments for these pathologies. METHODS: MenIN Study Group is a group of international experts treating and performing research on meniscus pathology and treatment. All MenIN Study Group members were asked to complete a survey aimed at establishing criteria for the optimal classification system for meniscal extrusion. Data obtained from the completed questionnaires were transferred into a spreadsheet and then analysed. All responses are presented as counts, percentages or means. RESULTS: Forty-seven (85.5%) MenIN Study Group members completed the survey and were included in this analysis. Key aspects recommended for inclusion in a comprehensive classification system for meniscal extrusion included laterality (93.6%), anatomical location (76.6%), patient age (76.6%), body mass index (BMI) (68.1%) and aetiology (68.1%). For classifying meniscal extrusion, 53.2% considered the distance in millimetres from the tibial plateau's outer margin as the most reliable measurement technique on imaging. Preferences for imaging modalities varied, with 44.7% favouring weight-bearing magnetic resonance imaging (MRI) and 36.2% opting for weight-bearing ultrasound due to its greater availability. Respondents advocated for a classification system addressing stability or progression of meniscal extrusion (66%), reducibility (53.2%), potential progression of knee osteoarthritis (OA) (83%), influencing treatment approaches (83%), a gradation system (83%), consideration of dynamic factors (66%), association with clinical outcomes and prognosis (76.6%) and investigation around centralization procedures (57.4%). CONCLUSIONS: In conclusion, the findings of this survey shed light on the global perspectives regarding meniscal extrusion classification. It was generally felt that a new classification of extrusion measured on MRI scans at the mid-tibial plateau should be developed, which considers factors such as laterality, anatomical location, age, BMI and aetiology. Additionally, the results support the integration of dynamic factors and clinical outcomes in MRI-based classifications to inform treatment approaches. LEVEL OF EVIDENCE: Level IV.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

Inflammatory synovial biomarkers and state of the tibiofemoral joint in the post-surgical settings: a narrative review.

Background and Objective: Knee surgery attempts to restore the native biomechanics of the knee, improve stability, and decrease the progression of osteoarthritis (OA). However, despite improvements in surgical techniques, tissue degradation and OA are common after knee surgery, occurring in higher rates in surgical knees compared to non-surgical knees. The aim of this study is to analyze previous literature to determine which synovial fluid biomarkers contribute to knee tissue degradation and decrease patient outcomes in the post-surgical setting of the knee. Methods: A narrative review of relevant literature was performed in July 2023. Studies reporting on synovial biomarkers associated with the post-surgical knee were included. Key Content and Findings: The literature reported that proinflammatory synovial biomarkers cause cartilage degradation and turnover which eventually leads to OA. The associated biomarkers are typically present prior to physical symptoms so understanding which one's correlate to OA is important for potential therapeutic treatments in the future. Studying the preoperative, early postoperative, and late postoperative synovial biomarkers will allow physicians to develop an improved understanding of how these biomarkers progress and correlate to knee tissue degradation and OA. This understanding could lead to further developments into potential treatment options. Research into inhibiting or reversing these inflammatory biomarkers to slow the progression of knee tissue degradation has already begun and has reported some promising results but is currently limited in scope. Conclusions: Synovial fluid biomarkers in the post-surgical knee setting may contribute to decreased patient outcomes and the progression of knee tissue degradation. There is no current consensus on which of these biomarkers are the most detrimental or associated with decreased patient outcomes. With an improved understanding of the individual biomarkers, potential personalized therapeutic treatment could be used by physicians in the future to improve patient outcomes after surgery.

The effect of nonsteroidal anti-inflammatory drug use on soft tissue and bone healing in the knee: a systematic review.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to mitigate pain and inflammation associated with musculoskeletal conditions; however, there is conflicting data on the adverse effects of these drugs on tissue and bone healing. The objective of this study was to investigate the effect of NSAIDs on the healing of knee, soft tissue, and bone. Methods: A systematic literature search was conducted across PubMed/MEDLINE, Excerpta Medical Database (Embase)/Ovid, and the Cochrane Central Register of Controlled Trials databases. Clinical, animal, and in vitro studies on the effect of NSAIDs on knee healing were included. Risk of bias assessment was performed using the Cochrane bias assessment tool and Methodological Index for Non-Randomized Studies scoring system for included clinical studies, and the Systematic Review Center for Laboratory Animal Experimentation assessment tool for all included animal studies. General study population characteristics, interventions used, NSAIDs utilized, outcome measures, and study results were analyzed using descriptive statistics. Results: Fifteen articles met the inclusion criteria. Of the 15 studies, there were three clinical, ten animal, and two in vitro studies. In clinical studies, nonselective cyclooxygenase (COX) inhibitors and selective COX-2 inhibitors did not cause a significant increase in failure of anterior cruciate ligament (ACL) reconstructions or meniscal repairs with NSAID administration pre-, peri-, or post-operatively in comparison to placebo or no NSAID administration. Among animal studies assessing COX-2 inhibitor effects on soft tissue, healing was impaired (2/4), delayed but unaffected (1/4), or unaffected (1/4). In animal studies assessing COX-1 inhibitors, ligament healing was either increased (1/4), unaffected (2/4), or impaired (1/4). Meanwhile, administration of non-selective COX inhibitors in animals did not affect soft tissue (3/3) and cartilage (1/1) healing. Two in vitro studies identified a negative outcome on patellar tendon and ACL cell proliferation or viability after non-selective COX inhibition and variable results after selective COX-2 inhibition. Conclusions: Animal studies on postoperative NSAID use after knee surgery suggest that administration of selective and nonselective COX-2 inhibitors may impair healing of soft tissue, bone and tendon-to-bone; however, further clinical studies are needed to better characterize dose and duration dependent risks of NSAIDs.

Effect of anti-inflammatory treatments on patient outcomes and concentrations of inflammatory modulators in the post-surgical and post-traumatic tibiofemoral joint setting: a narrative review.

Background and Objective: There are several anti-inflammatory therapeutic options that can be used in the context of post-surgical and post-traumatic knee settings. Each of these options carries with it certain benefits, as well as potential issues depending on the duration and administration of each therapy. An understanding of how these anti-inflammatory drugs modulate various biomarkers of inflammation is also necessary in understanding how they can affect patient and objective outcomes following acute knee injury or surgery. This review covers the many traditional therapeutic options that have been used in treating knee injuries, as well as some natural therapeutics that have shown anti-inflammatory properties. Methods: A current review of the literature was conducted and synthesized into this narrative review. Key Content and Findings: Many traditional anti-inflammatory therapeutics have been shown to be beneficial in both post-traumatic and post-surgical tibiofemoral joint settings at reducing inflammation and improving patient outcomes. However, many of these treatments have risks associated with them, which becomes problematic with prolonged, repeated administration. Natural anti-inflammatory compounds may also have some benefit as adjunctive treatment options in these settings. Conclusions: There are multiple different therapeutic options that can be used in acute knee settings, but the specific mechanism of injury or surgical context should be weighed when determining the best clinical approach.

Implications of drug intoxication on donor utilization and outcomes in liver transplantation.

INTRODUCTION: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). METHODS: The UNOS STAR database was evaluated for all potential donors and adult, first-time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1-year graft loss. RESULTS: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26-40 years, p < .001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015-2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p < .001). Among DBD donors, DI-COD was associated with superior 1-year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057-1.300) and CVA/stroke (HR 1.404, 95% CI 1.264-1.561, p < .001). Donor COD was not significantly associated with 1-year graft loss among DCD donors. CONCLUSIONS: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1-year graft survival compared to donors from trauma, CVA/stroke, and other COD.

Patterns of Failure in Patients With Borderline Resectable/Locally Advanced Pancreatic Cancer After Preoperative Chemotherapy and Stereotactic Body Radiation Therapy.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection. Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan-Meier overall survival and progression-free survival estimates were calculated. Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression. Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation.

Database Integration Correlates Street Crossing Design Strategies With Pedestrian Injury.

INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.

Expression network analysis of bovine skin infested with Rhipicephalus australis identifies pro-inflammatory genes contributing to tick susceptibility.

The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-naïve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR < 0.05), of which 212 were the target of at least 1866 transcription factors (TFs) expressed in skin. Regulatory impact factor (RIF) analysis identified 158 significant TFs (P < 0.05) of which GRHL3, and DTX1 were also DEGs in the experiment. Gene term enrichment showed the significant TFs and DEGs were enriched in processes related to immune response and biological pathways related to host response to infectious diseases. Interferon Type 1-stimulated genes, including MX2, ISG15, MX1, OAS2 were upregulated in low host resistance steers after repeated tick challenge, suggesting dysregulated wound healing and chronic inflammatory skin processes contributing to host susceptibility to ticks. The present study provides an assessment of the bovine skin transcriptome before and after repeated tick challenge and shows that the up-regulation of pro-inflammatory genes is a prominent feature in the skin of tick-susceptible animals. In addition, the identification of transcription factors with high regulatory impact provides insights into the potentially meaningful gene-gene interactions involved in the variation of phenotypes of bovine host resistance to ticks.