Validated numerical unrestrained occupant-seat crash scenarios for high-speed trains integrating experimental, computational, and inverse methods.

OBJECTIVE: Occupant impact safety is critical for train development. This paper proposes a systematic procedure for developing validated numerical occupant crash scenarios for high-speed trains by integrating experimental, computational, and inverse methods. METHODS: As the train interior is the most potentially injury-causing factor, the material properties were acquired by mechanical tests, and constitutive models were calibrated using inverse methods. The validity of the seat material constitutive model was further verified via drop tower tests. Finite element (FE) and multibody (MB) models of train occupant-seat interactions in frontal impact were established in LS-DYNA and MADYMO software, respectively, using the experimentally acquired materials/mechanical characteristics. Three dummy sled crash tests with different folding table and backrest configurations were conducted to validate the numerical occupant-seat models and to further assess occupant injury in train collisions. The occupant impact responses between dummy tests and simulations were quantitatively compared using a correlation and analysis (CORA) objective rating method. RESULTS: Results indicated that the experimentally calibrated numerical seat-occupant models could effectively reproduce the occupant responses in bullet train collisions (CORA scores >80%). Compared with the train seat-occupant MB model, the FE model could simulate the head acceleration with slightly more acceptable fidelity, however, the FE model CORA scores were slightly less than for the MB models. The maximum head acceleration was 30 g but the maximum HIC score was 17.4. When opening the folding table, the occupant's chest injury was not obvious, but the neck-table contact and "chokehold" may potentially be severe and require further assessment. CONCLUSIONS: This study demonstrates the value of experimental data for occupant-seat model interactions in train collisions and provides practical help for train interior safety design and formulation of standards for rolling stock interior passive safety.

Glycosaminoglycans: Roles in wound healing, formation of corneal constructs and synthetic corneas.

Maintaining the clarity of the cornea is essential for vision, and is achieved through an exquisite array of collagen fibrils and proteoglycans in the corneal stroma. Alterations in the identity and modifications of the glycosaminoglycans (GAGs) are seen both throughout the normal wound healing process and in pathological conditions resulting in corneal opacity. Understanding these changes has been essential for the development of corneal prostheses and corneal reconstruction. The goal of this review article is to summarize and consolidate research in the alterations seen in glycosaminoglycans in injured and hypoxic states, address the role of proteins that can regulate glycosaminoglycans in the corneal wound healing process, and apply these findings to the context of corneal restoration through reconstruction or the insertion of synthetic devices.

From injury to patterning-MAPKs and Wnt signaling in Hydra.

Hydra has a regenerative capacity that is not limited to individual organs but encompasses the entire body. Various global and integrative genome, transcriptome and proteome approaches have shown that many of the signaling pathways and transcription factors present in vertebrates are already present in Cnidaria, the sister group of Bilateria, and are also activated in regeneration. It is now possible to investigate one of the central questions of regeneration biology, i.e., how does the patterning system become activated by the injury signals that initiate regeneration. This review will present the current data obtained in Hydra and draw parallels with regeneration in Bilateria. Important findings of this global analysis are that the Wnt signaling pathway has a dual function in the regeneration process. In the early phase Wnt is activated generically and in a second phase of pattern formation it is activated in a position specific manner. Thus, Wnt signaling is part of the generic injury response, in which mitogen-activated protein kinases (MAPKs) are initially activated via calcium and reactive oxygen species (ROS). The MAPKs, p38, c-Jun N-terminal kinases (JNKs) and extracellular signal-regulated kinases (ERK) are essential for Wnt activation in Hydra head and foot regenerates. Furthermore, the antagonism between the ERK signaling pathway and stress-induced MAPKs results in a balanced induction of apoptosis and mitosis. However, the early Wnt genes are activated by MAPK signaling rather than apoptosis. Early Wnt gene activity is differentially integrated with a stable, ß-Catenin-based gradient along the primary body axis maintaining axial polarity and activating further Wnts in the regenerating head. Because MAPKs and Wnts are highly evolutionarily conserved, we hypothesize that this mechanism is also present in vertebrates but may be activated to different degrees at the level of early Wnt gene integration.

Chemistry and Function of Glycosaminoglycans in the Nervous System.

Proteoglycans, and especially their GAG components, participate in numerous biologically significant interactions with growth factors, chemokines, morphogens, guidance molecules, survival factors, and other extracellular and cell-surface components. These interactions are often critical to the basic developmental processes of cellular proliferation and differentiation, as well as to both the onset of disease sequelae and prevention of disease progression. In many tissues, proteoglycans and especially their glycosaminoglycan (GAG) components are mediators of these processes. The GAG family is characterized by covalently linked repeating disaccharides forming long unbranched polysaccharide chains. Thus far in higher eukaryotes, the family consists of chondroitin sulfate (CS), heparin/heparan sulfate (HS), dermatan sulfate (DS), keratan sulfate (KS) and hyaluronan (HA). All GAG chains (except HA) are characteristically modified by varying amounts of esterified sulfate. One or more GAG chains are usually found in nature bound to polypeptide backbones in the form of proteoglycans; HA is the exception. In the nervous system, GAG/proteoglycan-mediated interactions participate in proliferation and synaptogenesis, neural plasticity, and regeneration. This review focuses on the structure, chemistry and function of GAGs in nervous system development, disease, function and injury response.

Molecular characterization of the immediate wound response of the solitary ascidian Polycarpa mytiligera.

BACKGROUND: Injury response is key to successful regeneration. Yet, transcriptome analyses of injury response were performed only on a handful of regenerative organisms. Here, we studied the injury response of the solitary ascidian Polycarpa mytiligera, an emerging model system, capable of regenerating any body part. We used the siphon as a model for studying transcriptional changes following injury, and identified genes that were activated in the initial 24 hours post amputation (hpa). RESULTS: Highly conserved genes, such as bone morphogenetic protein-1 (BMP1), growth hormone secretagogue receptor (GHSR) and IL-17, were upregulated by 12 hpa, yet their expression was sustained only in non-regenerating tissue fragments. We optimized fluorescent in situ hybridization, and found that the majority of BMP1+ cells were localized to the rigid tunic that covers the animal. This highlights the importance of this tissue, particularly during injury response. BMP1 was overexpressed following injuries to other body regions, suggesting that it was a part of a common injury-induced program. CONCLUSION: Our study suggests that, initially, specific injury-induced genes were upregulated in P. mytiligera organs, yet, later, a unique transcriptional profile was observed only in regenerating tissues. These findings highlight the importance of studying diverse regenerating and non-regenerating organisms for complete understanding of regeneration.

Injury-induced MAPK activation triggers body axis formation in Hydra by default Wnt signaling.

Hydra's almost unlimited regenerative potential is based on Wnt signaling, but so far it is unknown how the injury stimulus is transmitted to discrete patterning fates in head and foot regenerates. We previously identified mitogen-activated protein kinases (MAPKs) among the earliest injury response molecules in Hydra head regeneration. Here, we show that three MAPKs-p38, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs)-are essential to initiate regeneration in Hydra, independent of the wound position. Their activation occurs in response to any injury and requires calcium and reactive oxygen species (ROS) signaling. Phosphorylated MAPKs hereby exhibit cross talk with mutual antagonism between the ERK pathway and stress-induced MAPKs, orchestrating a balance between cell survival and apoptosis. Importantly, Wnt3 and Wnt9/10c, which are induced by MAPK signaling, can partially rescue regeneration in tissues treated with MAPK inhibitors. Also, foot regenerates can be reverted to form head tissue by a pharmacological increase of ß-catenin signaling or the application of recombinant Wnts. We propose a model in which a ß-catenin-based stable gradient of head-forming capacity along the primary body axis, by differentially integrating an indiscriminate injury response, determines the fate of the regenerating tissue. Hereby, Wnt signaling acquires sustained activation in the head regenerate, while it is transient in the presumptive foot tissue. Given the high level of evolutionary conservation of MAPKs and Wnts, we assume that this mechanism is deeply embedded in our genome.

An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury.

BACKGROUND: The important contribution of glia to mechanisms of injury and repair of the nervous system is increasingly recognized. In stark contrast to the central nervous system (CNS), the peripheral nervous system (PNS) has a remarkable capacity for regeneration after injury. Schwann cells are recognized as key contributors to PNS regeneration, but the molecular underpinnings of the Schwann cell response to injury and how they interact with the inflammatory response remain incompletely understood. METHODS: We completed bulk RNA-sequencing of Schwann cells purified acutely using immunopanning from the naïve and injured rodent sciatic nerve at 3, 5, and 7 days post-injury. We used qRT-PCR and in situ hybridization to assess cell purity and probe dataset integrity. Finally, we used bioinformatic analysis to probe Schwann cell-specific injury-induced modulation of cellular pathways. RESULTS: Our data confirm Schwann cell purity and validate RNAseq dataset integrity. Bioinformatic analysis identifies discrete modules of genes that follow distinct patterns of regulation in the 1st days after injury and their corresponding molecular pathways. These findings enable improved differentiation of myeloid and glial components of neuroinflammation after peripheral nerve injury and highlight novel molecular aspects of the Schwann cell injury response such as acute downregulation of the AGE/RAGE pathway and of secreted molecules Sparcl1 and Sema5a. CONCLUSIONS: We provide a helpful resource for further deciphering the Schwann cell injury response and a depth of transcriptional data that can complement the findings of recent single cell sequencing approaches. As more data become available on the response of CNS glia to injury, we anticipate that this dataset will provide a valuable platform for understanding key differences in the PNS and CNS glial responses to injury and for designing approaches to ameliorate CNS regeneration.

A novel approach to investigate effects of front-end structures on injury response of e-bike riders: Combining Monte Carlo sampling, automatic operation, and data mining.

Transportation safety related to e-bikes is becoming more problematic with the growing popularity in recent decade years, however, rare studies focused on the protection for e-bike riders in traffic accidents. This paper aimed to investigate the relationship between vehicle front-end structures and rider's injury based on a novel approach including modeling, sampling, and analyzing. Firstly, a parametrized model for front-end structures of the vehicle was developed with nine parameters to realize the standardization of multi-body models of car to e-bike collision considering three stature riders and different impacting velocities. Secondly, a framework, combining Monte Carlo sampling for twelve initial variables and automatic operation for 1000 impact simulations, was built to obtain valid results automatically and then to construct a big dataset. Finally, according to the sensitive variables to riders' vulnerable regions, the decision tree algorithm was further adopted to develop the decision or prediction model on injuries. The novel approach achieved the stochastical generation of vehicle shapes and the automatic operation of multi-body models. The results showed that the rider's head, pelvis, and thighs were more vulnerable to being injured in the car to e-bike perpendicular accidents. The three decision tree models (HIC15, lateral force of pelvis, bending moment of upper leg) were validated to be accurate and reliable according to the confusion matrix with the precision of more than 80% and the receiver operating characteristic curves (ROC) with the under area more than 85%. Based on decision tree models, not only the effects of front-end structural parameters on the corresponding injury but also the interaction mechanism between various variables can be clearly interpreted. Each route from the same root node to hierarchical middle nodes then to various leaf nodes represented a decision-making process. And the different branches under the same decision node directly illustrated the correlation between variables, which is highly readable and comprehensible. During the safety performance design of front-end structures, the rational value of variables could be decided according to decision routes that resulted in lower injury levels; Even if the accident was inevitable, the collision parameters could be controlled within a certain range for the least injury according to the prediction rules. Based on the novel framework coupling Monte Carlo sampling and automatic operation, it's foreseeable to apply the parametric and standard car-to-e-bike collision models to develop the virtual test system and to optimize front-end shapes for rider's protection.

Interorgan crosstalk mechanisms in disease: the case of acute kidney injury-induced remote lung injury.

Homoeostasis and health of multicellular organisms with multiple organs depends on interorgan communication. Tissue injury in one organ disturbs this homoeostasis and can lead to disease in multiple organs, or multiorgan failure. Many routes of interorgan crosstalk during homoeostasis are relatively well known, but interorgan crosstalk in disease still lacks understanding. In particular, how tissue injury in one organ can drive injury at remote sites and trigger multiorgan failure with high mortality is poorly understood. As examples, acute kidney injury can trigger acute lung injury and cardiovascular dysfunction; pneumonia, sepsis or liver failure conversely can cause kidney failure; lung transplantation very frequently triggers acute kidney injury. Mechanistically, interorgan crosstalk after tissue injury could involve soluble mediators and their target receptors, cellular mediators, in particular immune cells, as well as newly identified neuro-immune connections. In this review, I will focus the discussion of deleterious interorgan crosstalk and its mechanistic concepts on one example, acute kidney injury-induced remote lung injury.

A Comparison of the Mid-Size Male THOR and Hybrid III ATDs in Vehicle Frontal Crash Tests.

In order to evaluate the THOR-50M as a front impact Anthropomorphic Test Device (ATD) for vehicle safety design, the ATD was compared to the H3-50M in matching vehicle crash tests for 20 unique vehicle models from 2 vehicle manufacturers. For the belted driver condition, a total of fifty-four crash tests were investigated in the 56.3 km/h (35 mph) front rigid barrier impact condition. Four more tests were compared for the unbelted driver and right front passenger at 40.2 km/h (25 mph) in the flat frontal and 30-degree right oblique rigid barrier impact conditions. The two ATDs were also evaluated for their ability to predict injury risk by comparing their fleet average injury risk to Crash Investigation Sampling System (CISS) accident data for similar conditions. The differences in seating position and their effect on ATD responses were also investigated. This study showed that the belted THOR-50M injury responses were higher than the H3-50M by 25%-180%, in all reported ATD responses, except chest acceleration. For one unbelted condition, the THOR-50M reported 200%-300% higher neck responses than the H3-50M, primarily due to head contact to the roof structure in a mid-sized sedan. The THOR-50M overpredicted the injury risk based on chest deflection compared to the CISS accident data by at least a factor of 4 times. The THOR-50M also overpredicted the injury risk based on BrIC by at least a factor of 10 times. Future work is needed to investigate these overpredictions with respect to ATD construction, injury risk curves, and seating procedures.

Age-Related Changes in the Microvascular Density of the Human Meniscus.

BACKGROUND: The microvascular anatomy of the meniscus of the human knee is regarded as a crucial factor in the injury response. Previous studies have investigated the zone-dependent distribution pattern, but no quantitative data exist on vascular density and its age-related changes. HYPOTHESIS/PURPOSE: The aim of the present study was to histologically analyze the vascular anatomy of the meniscus as a function of age. It was hypothesized that vascular density would decrease with increasing age. STUDY DESIGN: Descriptive laboratory study. METHODS: Human menisci were retrieved from patients who underwent tumor resection or who received total knee replacement because of osteoarthritis. A total of 51 menisci were collected from 28 patients over 9 years (mean age, 25.6 ± 20.4 years; range 3-79 years). Immunohistological staining (alpha-smooth muscle actin) in combination with serial sections and standardized software-based contrast detection were used for the quantitative analysis. Data were analyzed using multiple t tests and the analysis of variance for trends, with a statistical significance level of P < .05. RESULTS: The overall vascular density in the meniscus was lower in the 61- to 80-year age group than in the age groups of 0 to 10, 11 to 20, and 21 to 30 years (P < .01). A negative linear trend was detected with increasing age (slope, -0.007; P = .016). Within the red-white (RW) zone, a low vessel density was detected for the age groups of 0 to 10 and 11 to 20 years. Beyond these age groups, no vasculature was found in the RW zone. For the white-white (WW) zone, no vessel formations were noted in any age group. Almost 95% of the vessels in the meniscus were located in the capsule. CONCLUSION: This study reports quantitative histological data for microvascular anatomy as a function of age in a broad cohort of human knee menisci. The overall vascular density decreased with increasing age. No vessel formations were detected in the RW and WW zones after adolescence. Additionally, the capsule is far more densely vascularized than any other part of the meniscus. CLINICAL RELEVANCE: Vascular density might be an additional factor to consider, along with tear location and patient age, for future treatment options.

Lower Extremity Impact and Injury Responses of Male and Female PMHS to High-Rate Vertical Loading.

Whole-body PMHS (Post Mortem Human Surrogate) testing was conducted on the Accelerative Loading Fixture (ALF), which is designed to generate floor and seat loading conditions at the level, rate, location, direction, and extent seen in UBB (Underbody Blast). The overarching goal of this research effort was to examine potential differences in the lower extremity response of females and males under UBB conditions. The ALF consists of an occupant platform that is driven upward by the detonation of an explosive charge. The floor plate undergoes plastic deformation. The occupant platform supports two rigid seats for surrogates. Twenty un-embalmed PMHS were tested, including 50th-percentile males, 75th-percentile females, and 5th-percentile females. Two test series were conducted. Series A had a target floor speed of 8 m/s (2-ms time-to-peak) with a target seat speed of 5 m/s (4-ms time-to-peak). Series B had a target floor speed of 20 m/s (2-ms time-to-peak) with a target seat speed of 4 m/s (7-ms time-to-peak). Major damage occurred to the femur, tibia, fibula, talus, and calcaneus. Lower extremity damage type, incidence, and extent varied between the two sexes. Fifty-percent probability of calcaneus fracture for less than 3-ms time-to-peak is associated with a 781-g peak tibia vertical acceleration for 50th-percentile males, 650-g for 75th-percentile females, and 396-g for 5th-percentile females. Fifty-percent probability of calcaneus fracture, regardless of time-to-peak, is associated with a 368-g peak femur vertical acceleration for 50th-percentile males, 332-g for 75th-percentile females, and 218-g for 5th-percentile females. These results show differences in kinematics and damage outcome between female and male PMHS in UBB conditions. These findings will inform future decisions regarding the requirements for test capabilities that incorporate the female Warfighter. Ultimately, advancements can be made in injury assessment tools such as improved physical surrogates, injury assessment and prediction criteria, modeling and simulation capabilities, test methods, and the optimization of military ground vehicles, personal protective equipment, and injury countermeasures.

An image analysis method for regionally defined cellular phenotyping of the Drosophila midgut.

The intestine is divided into functionally distinct regions along the anteroposterior (A/P) axis. How the regional identity influences the function of intestinal stem cells (ISCs) and their offspring remain largely unresolved. We introduce an imaging-based method, "Linear Analysis of Midgut" (LAM), which allows quantitative, regionally defined cellular phenotyping of the whole Drosophila midgut. LAM transforms image-derived cellular data from three-dimensional midguts into a linearized representation, binning it into segments along the A/P axis. Through automated multivariate determination of regional borders, LAM allows mapping and comparison of cellular features and frequencies with subregional resolution. Through the use of LAM, we quantify the distributions of ISCs, enteroblasts, and enteroendocrine cells in a steady-state midgut, and reveal unprecedented regional heterogeneity in the ISC response to a Drosophila model of colitis. Altogether, LAM is a powerful tool for organ-wide quantitative analysis of the regional heterogeneity of midgut cells.

Cell-Type-Specific Gene Regulatory Networks Underlying Murine Neonatal Heart Regeneration at Single-Cell Resolution.

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Neonatal heart regeneration is orchestrated by multiple cell types intrinsic to the heart, as well as immune cells that infiltrate the heart after injury. To elucidate the transcriptional responses of the different cellular components of the mouse heart following injury, we perform single-cell RNA sequencing on neonatal hearts at various time points following myocardial infarction and couple the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single-cell ATAC sequencing exposes underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types and reveals extracellular mediators of cardiomyocyte proliferation, angiogenesis, and fibroblast activation. Together, our data provide a transcriptional basis for neonatal heart regeneration at single-cell resolution and suggest strategies for enhancing cardiac function after injury.

GAP-43 and BASP1 in Axon Regeneration: Implications for the Treatment of Neurodegenerative Diseases.

Growth-associated protein-43 (GAP-43) and brain acid-soluble protein 1 (BASP1) regulate actin dynamics and presynaptic vesicle cycling at axon terminals, thereby facilitating axonal growth, regeneration, and plasticity. These functions highly depend on changes in GAP-43 and BASP1 expression levels and post-translational modifications such as phosphorylation. Interestingly, examinations of GAP-43 and BASP1 in neurodegenerative diseases reveal alterations in their expression and phosphorylation profiles. This review provides an overview of the structural properties, regulations, and functions of GAP-43 and BASP1, highlighting their involvement in neural injury response and regeneration. By discussing GAP-43 and BASP1 in the context of neurodegenerative diseases, we also explore the therapeutic potential of modulating their activities to compensate for neuron loss in neurodegenerative diseases.

A Functional Non-coding RNA Is Produced from xbp-1 mRNA.

The xbp-1 mRNA encodes the XBP-1 transcription factor, a critical part of the unfolded protein response. Here we report that an RNA fragment produced from xbp-1 mRNA cleavage is a biologically active non-coding RNA (ncRNA) essential for axon regeneration in Caenorhabditis elegans. We show that the xbp-1 ncRNA acts independently of the protein-coding function of the xbp-1 transcript as part of a dual output xbp-1 mRNA stress response axis. Structural analysis indicates that the function of the xbp-1 ncRNA depends on a single RNA stem; this stem forms only in the cleaved xbp-1 ncRNA fragment. Disruption of this stem abolishes the non-coding, but not the coding, function of the endogenous xbp-1 transcript. Thus, cleavage of the xbp-1 mRNA bifurcates it into a coding and a non-coding pathway; modulation of the two pathways may allow neurons to fine-tune their response to injury and other stresses.

Functions of histone modifications and histone modifiers in Schwann cells.

Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion by demyelinating and converting into repair cells that secrete neurotrophic factors and guide axons back to their former target to finally remyelinate regenerated axons. The different steps of SC development and their role in the maintenance of PNS integrity and regeneration after lesion are controlled by various factors among which transcription factors and chromatin-remodeling enzymes hold major functions. In this review, we discussed how histone modifications and histone-modifying enzymes control SC development, maintenance of PNS integrity and response to injury. The functions of histone modifiers as part of chromatin-remodeling complexes are discussed in another review published in the same issue of Glia.

The Trichoderma atroviride Strains P1 and IMI 206040 Differ in Their Light-Response and VOC Production.

Trichoderma atroviride is a strong necrotrophic mycoparasite antagonizing and feeding on a broad range of fungal phytopathogens. It further beneficially acts on plants by enhancing growth in root and shoot and inducing systemic resistance. Volatile organic compounds (VOCs) are playing a major role in all those processes. Light is an important modulator of secondary metabolite biosynthesis, but its influence has often been neglected in research on fungal volatiles. To date, T. atroviride IMI 206040 and T. atroviride P1 are among the most frequently studied T. atroviride strains and hence are used as model organisms to study mycoparasitism and photoconidiation. However, there are no studies available, which systematically and comparatively analyzed putative differences between these strains regarding their light-dependent behavior and VOC biosynthesis. We therefore explored the influence of light on conidiation and the mycoparasitic interaction as well as the light-dependent production of VOCs in both strains. Our data show that in contrast to T. atroviride IMI 206040 conidiation in strain P1 is independent of light. Furthermore, significant strain- and light-dependent differences in the production of several VOCs between the two strains became evident, indicating that T. atroviride P1 could be a better candidate for plant protection than IMI 206040.

The retinal environment induces microglia-like properties in recruited myeloid cells.

BACKGROUND: Microglia are essential to the development of the CNS and its homeostasis. Our prior findings suggested a niche model to describe the behaviors of retinal microglia. Here, we ask whether new myeloid cells recruited to the retina are constrained to resemble endogenous microglia morphologically and functionally. METHODS: Use of CD11cDTR/GFP transgenic mouse allowed identification of two niches of retinal microglia distinguished by being GFPlo or GFPhi. We also used transgenic mice in which CX3CR1+ cells expressed YFP and were depletable following tamoxifen-induced expression of diphtheria toxin subunit A. We employed several ablation and injury stimulation protocols to examine the origin and fate of myeloid cells repopulating the retina. Analysis of retinal myeloid cells was done by microscopy, flow cytometry, and qRT-PCR. RESULTS: We found that the origin of new GFPhi and GFPlo myeloid cells in the retina of CD11cDTR/GFP mice, whether recruited or local, depended on the ablation and stimulation protocols. Regardless of origin, new GFPlo and GFPhi retinal myeloid cells were CD45medCD11b+Ly6G-Ly6CloIba1+F4/80+, similar to endogenous microglia. Following tamoxifen-induced diphtheria toxin ablation, myeloid cell repopulation differed in the retina compared to the brain and optic nerve. Stimulation of replacement GFPhi cells was substantially attenuated in repopulating retinas after tamoxifen-induced diphtheria toxin ablation compared to control or radiation-ablated mice. In radiation bone marrow chimeric mice, replacement GFPhi myeloid cells from the circulation were slow to repopulate the retina unless stimulated by an optic nerve crush injury. However, once stimulated, recruited GFPhi cells were found to concentrate on injured retinal ganglion cells and were morphologically similar to GFPhi cells in non-ablated control CD11cDTR/GFP mice. CONCLUSIONS: The results support the idea that GFPhi cells in the CD11cDTR/GFP mouse, whether recruited or from resident microglia, mark a unique niche of activated retinal myeloid cells. We conclude that the retinal environment has a potent influence on the function, morphology, and proliferative capacity of new myeloid cells regardless of their origin, compelling them to be equivalent to the endogenous microglia.

Running status and history: A self-report study.

OBJECTIVES: The purpose of the current study was to compare injury and running history among current and former runners who consider themselves either injured or uninjured. DESIGN: Cross-sectional survey. SETTING: Online survey, available to any individuals over the age of 18 who currently run (runners) or who once ran regularly but are no longer running (former runners). PARTICIPANTS: 312 participants (age 38 ±â€¯12 years, 219 males, 89 females, 4 did not disclose) completed the survey. MAIN OUTCOME MEASURES: This study assessed injury incidence, consequences of injury such as time off, and reported injury diagnoses and treatments. Chi-square and frequency analyses were calculated to describe running status, injury counts, and response to injury. RESULTS: Most participants (80%) reported 1 + running injury. 775 total injuries were reported. The four most common injuries were iliotibial band syndrome (34%), plantar fasciitis (30%), strained thigh/hip muscle (25%), and medial tibial stress syndrome (22%). About 40% of participants continued to run with these injuries. CONCLUSIONS: Injury frequencies (80%) agreed with those reported in the literature. The results of this study also support the notion that running injuries exist on a continuum of severity and that the individual response to injury is complex and determined by various factors.