Repeat Injury Research Articles

Review of Assessment Scales for Diagnosing and Monitoring Sports-related Concussion.

Sports-related concussion has emerged as a public health crisis due to increased diagnosis of the condition and increased participation in organized and recreational athletics worldwide. Under-recognition of concussions can lead to premature clearance for athletic participation, leaving athletes vulnerable to repeat injury and subsequent short- and long-term complications. There is overwhelming evidence that assessment and management of sports-related concussions should involve a multifaceted approach. A number of assessment criteria have been developed for this purpose. It is important to understand the available and emerging diagnostic testing modalities for sports-related concussions. The most commonly used tools for evaluating individuals with concussion are the Post-Concussion Symptom Scale (PCSS), Standard Assessment of Concussion (SAC), Standard Concussion Assessment Tool (SCAT3), and the most recognized computerized neurocognitive test, the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). The strengths and limitations of each of these tools, and the Concussion Resolution Index (CRI), CogSport, and King-Devick tests were evaluated. Based on the data, it appears that the most sensitive and specific of these is the ImPACT test. Additionally, the King-Devick test is an effective adjunct due to its ability to test eye movements and brainstem function.

Effects of repeated nerve injuries at different time intervals on functional recovery and nerve innervation

Effects of repeated nerve injuries on functional recovery and nerve innervation were examined in rodents. Crush injuries of the sciatic nerve were inflicted on adult rats and repeated twice or thrice at different time intervals of 1, 2, 3, and 4 weeks. Motor function was assessed by the static sciatic index at 1, 7, 14, 21, 28, 35, 42, 49, and 56 days after the final crush. The rates of nerve innervation of the tibialis anterior muscle, a main muscle innervated by the common peroneal nerve, were evaluated by the quantification of βIII-tubulin-positive nerve terminals and α-bungarotoxin-positive acetylcholine receptors 21 and 56 days after the final crush of triple nerve injuries at 1-, 2-, 3-, and 4-week intervals. Compared with single nerve crush injury, delayed recovery of motor function was observed in repeated crush injuries. In addition, recoveries in the triple crush groups were slower than those in the double crush groups. The rates of reinnervation were lower in the triple crush groups than in the single crush groups, both at 21 days (single: 59.7%; triple: 54.1%–56.1%) and 56 days (single: 88.8%; triple: 72.5%–83.0%) after the final crush, except in the groups with 1-week (triple: 73.8%) and 2-week (triple: 70.5%) intervals at 21 days after the final crush. We concluded that the recovery of motor function was delayed according to the number of repetitions of crush injuries, and that the rates of nerve innervation were still low in the triple crush groups 8 weeks after the final crush.

Combining Vγ9Vδ2 T Cells with a Lipophilic Bisphosphonate Efficiently Kills Activated Hepatic Stellate Cells.

Activated hepatic stellate cells (aHSCs) are now established as a central driver of fibrosis in human liver injury. In the presence of chronic or repeated injury, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) can occur, so there is interest in down-regulating aHSCs activity in order to treat these diseases. Here, we report that Vγ9Vδ2 T cells are reduced in patients with liver cirrhosis, stimulating us to investigate possible interactions between Vγ9Vδ2 T cells and aHSCs. We find that Vγ9Vδ2 T cells kill aHSCs and killing is enhanced when aHSCs are pretreated with BPH-1236, a lipophilic analog of the bone resorption drug zoledronate. Cytotoxicity is mediated by direct cell-to-cell contact as shown by Transwell experiments and atomic force microscopy, with BPH-1236 increasing the adhesion between aHSCs and Vγ9Vδ2 T cells. Mechanistically, BPH-1236 functions by inhibiting farnesyl diphosphate synthase, leading to accumulation of the phosphoantigen isopentenyl diphosphate and recognition by Vγ9Vδ2 T cells. The cytolytic process is largely dependent on the perforin/granzyme B pathway. In a Rag2−/−γc−/− immune-deficient mouse model, we find that Vγ9Vδ2 T cells home-in to the liver, and when accompanied by BPH-1236, kill not only orthotopic aHSCs but also orthotopic HCC tumors. Collectively, our results provide the first proof-of-concept of a novel immunotherapeutic strategy for the treatment of fibrosis–cirrhosis–HCC diseases using adoptively transferred Vγ9Vδ2 T cells, combined with a lipophilic bisphosphonate.

Risk Factors for Lower Extremity Overuse Injuries in Female Youth Soccer Players.

Background:Youth soccer injuries are common and of increasing concern, with sport specialization occurring at younger ages. Limited research is available regarding overuse injuries and risk factors in young female athletes.Purpose:To identify the number and rate of overuse injuries in female soccer players (ages 12-15 years), describe the anatomic location and type of injury, and evaluate contributing risk factors.Study Design:Case-control study; Level of evidence, 3.Methods:A total of 351 female youth soccer players, ages 12 to 15 years, from Washington State were evaluated from 2008 to 2012. Players with lower extremity overuse injuries were identified through weekly emails and were interviewed by telephone to obtain data on injury type and body region. We evaluated the association between overuse injuries and preseason risk factors, including joint hypermobility, hip and knee muscle strength, and jump biomechanics, using Poisson regression to estimate relative risk (RR) and 95% CIs.Results:The incidence rate for first-time lower extremity overuse injuries was 1.7 per 1000 athlete-exposure hours (AEH; 95% CI, 1.4-2.2), and that for repeat injuries was 3.4 per 1000 AEH (95% CI, 2.1-5.6). Knee injuries accounted for 47% of overuse injuries. Increased valgus was associated with a 3.2-fold increased risk (95% CI, 1.52-6.71) for knee injury. A 1–standard deviation (SD) increase in hamstring strength was associated with a 35% decreased risk (RR, 0.65; 95% CI, 0.46-0.91) for overuse knee injuries, and a 1-SD increase in quadriceps strength was associated with a 30% decreased risk (RR, 0.70; 95% CI, 0.50-0.98). A 1-SD increase in hip flexor strength was associated with a 28% decreased risk (RR, 0.72; 95% CI, 0.51-1.00) for overuse knee injuries, and a 1-SD increase in external rotation strength was associated with a 35% decreased risk (RR, 0.65; 95% CI, 0.46-0.91). Playing on more than 1 soccer team was associated with a 2.5-fold increased risk (95% CI, 1.08-5.35) for overuse knee injuries, and participating in other physical activities was associated with a 61% decreased risk (odds ratio, 0.39; 95% CI, 0.15-0.81).Conclusion:In this study, lower extremity overuse injuries in female youth soccer players affected primarily the knee. Lower knee separation distance, decreased lower extremity strength, and playing on more than 1 soccer team increased injury risk.

Anterior Cruciate Ligament Injury—and Repeat Injury

Research Article| September 01 2017 Anterior Cruciate Ligament Injury—and Repeat Injury AAP Grand Rounds (2017) 38 (3): 31. https://doi.org/10.1542/gr.38-3-31 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Anterior Cruciate Ligament Injury—and Repeat Injury. AAP Grand Rounds September 2017; 38 (3): 31. https://doi.org/10.1542/gr.38-3-31 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: anterior cruciate ligament injuries, reinjuries, anterior cruciate ligament reconstruction Source: Dekker TJ, Godin JA, Dale KM, et al. Return to sport after pediatric anterior cruciate ligament reconstruction and its effect on subs equent anterior cruciate ligament injury. J Bone Joint Surg Am. 2017; 99(11): 897– 904; doi: https://doi.org/10.2106/JBJS.16.00758Google Scholar Investigators from Duke University conducted a retrospective study to assess the risk of subsequent ACL injury after primary ACL reconstruction surgery in children and adolescents. Eligible study participants were youth <18 years old undergoing primary ACL reconstruction at the authors’ institution between 2006 and 2013 and were identified by using CPT® codes for ACL reconstruction. The medical records of identified patients were reviewed, and demographic data and clinical information were abstracted. Preoperative radiographs of study participants were reviewed, and physeal status (open or closed) was determined. Standardized phone interviews conducted ≥2 years after the index ACL reconstruction were conducted. Data collected during the interview included pre-and postoperative sports participation, time to return to sports, whether a subsequent ACL injury occurred, and time from initial surgery to subsequent injury. Cox regression was used to identify potential risk factors for subsequent ACL injury; risk factors assessed included time to return to sports, return to a high-risk sport (defined as football, basketball, lacrosse, and soccer), physeal status, and type of graft used for index ACL reconstruction. Among 112 eligible patients, complete follow-up data were available for 85 (76%). The mean age of study patients was 13.9 years (range, 6–17 years), and 60% were female. Prior to their initial ACL injury, all study patients participated in sports, with 35% competing in basketball and 28% playing soccer. At the time of surgery, 77% had open physes. After ACL reconstruction, 77 youth (90%) returned to sports. After their primary ACL reconstruction, 27 study participants (32%) sustained a second ACL injury, including 16 patients who injured the ipsilateral ACL and 11 who injured the contralateral side; 1 youth had a tear on both sides. Among the risk factors for subsequent ACL injury assessed in multivariate analyses, only an increased time to return to sports was associated with a decreased risk of a second ACL injury after the initial ACL reconstruction (hazard ratio per month of additional delay in returning to sports = 0.87, P = .04). For youth who had a second ACL tear, mean time from index surgery until return to sports was 8.9 months ± 2.5, compared to 9.9 months ± 3.4 for those who had not experienced a second injury at the time of follow-up. The authors conclude that among youth undergoing ACL reconstruction, there is a substantial risk of a second ACL injury. Dr Hennrikus has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. ACL reconstruction is increasingly common in children. The increasing prevalence of ACL injuries is thought to be due to year-round youth sports participation and early sport specialization.1 Nonsurgical treatment of... You do not currently have access to this content.

Modeling the Long-Term Consequences of Repeated Blast-Induced Mild Traumatic Brain Injuries.

Repeated mild traumatic brain injury (rmTBI) caused by playing collision sports or by exposure to blasts during military operations can lead to late onset, chronic diseases such as chronic traumatic encephalopathy (CTE), a progressive neurodegenerative condition that manifests in increasingly severe neuropsychiatric abnormalities years after the last injury. Currently, because of the heterogeneity of the clinical presentation, confirmation of a CTE diagnosis requires post-mortem examination of the brain. The hallmarks of CTE are abnormal accumulation of phosphorylated tau protein, TDP-43 immunoreactive neuronal cytoplasmic inclusions, and astroglial abnormalities, but the pathomechanism leading to these terminal findings remains unknown. Animal modeling can play an important role in the identification of CTE pathomechanisms, the development of early stage diagnostic and prognostic biomarkers, and pharmacological interventions. Modeling the long-term consequences of blast rmTBI in animals is especially challenging because of the complexities of blast physics and animal-to-human scaling issues. This review summarizes current knowledge about the pathobiologies of CTE and rmbTBI and discusses problems as well as potential solutions related to high-fidelity modeling of rmbTBI and determining its long-term consequences.

EXPERIENCE OF REHABILITATION THE ATHLETES AFTER SURGICAL INTERVENTION ON THE ACHILLES TENDON

Achilles tendon injury frequency increases. The lack of standardized methods of rehabilitation after surgery on the Achilles tendon leading to increased risk of repeat injury tendon and reduces the possibility return to physical activity. Recovery of function the main task of rehabilitation programs, especially when working with athletes. We have a program of rehabilitation of 147 patients was per- formed after surgery on the Achilles tendon, which began from the first day after the operation and was as much as possible early onset of axial load.

A sliding hip screw augmented with 2 screws is biomechanically similar to an inverted triad of cannulated screws in repair of a Pauwels type-III fracture

ObjectivePauwels III femoral neck fractures are highly unstable. These fractures are commonly treated with three cannulated screws or sliding hip screw (SHS) implants, however high rates of non-union persist. A hybrid SHS construct has recently been proposed. The objective of the study was to compare this construct to the familiar inverted triad of cannulated screws and to a single SHS. MethodsFourth generation biomechanical femur analogs were used to create a highly repeatable injury model. The hybrid SHS construct contained a SHS with two superior cannulated screws in an inverted triangle configuration. Eight samples for each construct were biomechanically evaluated and the results compared using ANOVA (p<0.05). ResultsThe cannulated triad and hybrid SHS provided similar stiffness and fracture gap motion. The single SHS exhibited significantly lower stiffness and larger fracture plane diastasis than either the inverted triangle of cannulated screws or hybrid SHS (p<0.05). None of the constructs exhibited catastrophic failure during cyclic loading nor under loading up to 2.5 times body weight. ConclusionsThe single SHS provided the least stable fracture fixation, while the inverted triad and hybrid SHS constructs were mechanically similar. The fracture repair simulated here illustrates how these repairs have the potential to return near pre-fracture strength in ideal conditions with young, healthy bone. However; in clinical situations where comminution impairs load transfer through the cortices the hybrid SHS may be the most favorable option.

5 Year Survival of Endoscopic ACL Reconstruction with Live Donor Hamstring Tendon Allograft in Juveniles and Adolescents

Introduction:ACL reconstruction with autografts in the young is associated a higher incidence of repeat injury when compared to adults. This led the authors to consider alternative graft material for the ACL deficient young population. This study was performed to assess the survival of ACL reconstruction with a living related hamstring tendon autograft in a large series of juveniles and adolescents.Aim:To determine the survival of the ACL graft and the contralateral ACL (CACL) after primary ACL reconstruction with living donor allograft in patients aged < 18 years and to identify the factors that increase the odds of subsequent ACL injuries.Methods:Patients having undergone primary ACL reconstruction with a living donor hamstring tendon allograft at age <18 years between 2005 and 2014 included in a prospective database were considered for this study. Patients completed a subjective survey involving the International Knee Documentation Committee (IKDC) questionnaire in addition to questions regarding current symptoms, further ACL injuries, family history of ACL injury, and current level of activity.Results:A total of 218 adolescents (mean age 14.7, age range, 8-17 years) met the inclusion criteria and were reviewed at a mean of 48 months after surgery. Of these, there were 51 ACL graft ruptures (23%) and 26 contralateral ACL ruptures (12%). The 1, 2 and 5 year survival of the ACL graft was 88%, 80% and 74%. The 1, 2 and 5 year survival of the contralateral ACL was 99%, 93% and 85%. Survival of the ACL graft was more favorable in those with open growth plates (93, 90, 85 at 1,2 and 5 survival) compared to closed growth plates (86, 75, 68 at 1,2 and 5 year survival), odds ratio 2.3 (95% CI 1.1 to 4.8, p=0.03). A return to preinjury level of activity was reported by 79%, and the mean IKDC score was 92 of a possible 100. A positive family history of ACL injury was present in 35%.Conclusion:Further injury after ACL reconstruction in the young presents a challenging problem. ACL reconstruction using a living related donor allograft is associated with high rates of return to sport and good subjective outcomes. This technique may be considered a viable option for ACL reconstruction in the young patient with open growth plates, but does not appear to reduce further injury in older adolescents.

Modeling cellular network dynamics of liver homeostatic renewal

Recent experimental studies identified specific subpopulations of self‐renewing hepatocytes with ability to populate the liver during homeostatic maintenance of the tissue. It remains an open question as to how this process of precursor transformation into mature hepatocytes is regulated by molecular pathways and tissue microenviroment to yield robust homeostatic renewal. We explored the contribution of putative control mechanisms that yield robustness to the renewal process by developing and analyzing a computational model of liver homeostatic renewal that considers a cellular network of precursor cells and mature hepatocytes. We demonstrate that the renewal network without feedback and nonlinear dynamics cannot maintain liver tissue in response to repeated injury. We modified the model to consider multiple alternatives including capacity constraints on proliferation, inhibition of precursor proliferation and transformation by mature hepatocytes, and putative precursor replenishment from non‐hepatocyte sources. We followed a Design of Experiments approach to investigate the system dynamics under all possible combinations of feedback configurations, specifically characterizing recovery of precursor and mature hepatocyte populations in response to a wide variety of disturbances. This unbiased exploration led us to identify a model configuration that is most robust in maintaining liver homeostasis. We compared the dynamics of the most robust model configuration with the available experimental data on the effects of hepatocyte senescence and stem cell transplantation on liver tissue renewal. We investigated the dynamics of the homeostatic renewal network in response to chronic repeated injury. Our results suggest that increasing frequency and magnitude of chronic repeated injury destabilizes the liver homeostasis within several months, which is inconsistent with epidemiological observations of a much slower decay of liver function over several years. We interpret these findings as suggestive of the presence of additional stabilizing controls potentially by the non‐parenchymal cells. We modified the model to include manipulation of the liver microenvironment signals by the liver non‐parenchymal cells as an additional layer of feedback control over hepatocyte levels. Our simulations and model analyses lead us to predict that robust homeostatic balance of hepatocytes is achieved by a combination of intrinsic system stability and control by non‐parenchymal cells. Taken together, our computational modeling study suggests that homeostatic renewal and maintenance of liver tissue is achieved through a coordinated regulation of the process by a combination of cell‐intrinsic and intercellular feedback control mechanisms.Support or Funding InformationResearch Support: R01 AA018873, T32 AA007463, F31 AA023445

SPORTS SPECIALIZED RISKS FOR REINJURY IN YOUNG ATHLETES: A 2+ YEAR CLINICAL PROSPECTIVE EVALUATION

BackgroundWe previously demonstrated an independent risk of sports specialization in young athletes. However, there is no longitudinal study on the risks of sports specialization and reinjury in young athletes.ObjectiveTo determine...

Elettrocortical spectral analysis and fractal methods for assessing the effects of unilateral brain injury on rat cerebellum

We used electrocortical spectral analysis and fractal methods for assessing the effects of unilateral, single brain injury on cerebellum. Cerebellar electrocortical activity was recorded in control state (before the injury) and after a single brain injury of the cerebellar cortex in anesthetized rats. We noticed that the mean power in gamma high-frequency domain (32-128 Hz) of the cerebellum, was increased after the first brain injury, while after a two-week recovery, it was larger than before the injury. The unilateral brain injury induced a permanent increase of the mild gamma activity in both the left and the right side of cerebellum cortex, but there was no further increase after the lesion was repeated. Our recent electrophysiological study on the cerebellum (Culic et al., 2005) suggested that the mean power spectra of the cerebellar cortical activity in the gamma frequency range might be the indicator of acute single focal brain injury. However, there is insufficient information on the effects of the repeated brain injury on the cerebellar electrocortical activity and morphology. There was no significant difference between the absolute and the relative mean power of the left and the right paravermal cortical activity (before, as well as, after the injury), in each of the animals tested afterwards, but there were differences between the left and the right side of cerebellum in experimental animals. Repeated injury of the cerebellar cortical areas, is strengthened by morphological changes in the cerebellar hemisphere, and shows a decrease in delta and an increase in gamma range.

Hazard Ratio and Repeat Injury for Dementia in Patients With and Without a History of Traumatic Brain Injury: A Population-Based Secondary Data Analysis in Taiwan.

The impact of traumatic brain injury (TBI) on the pathogenic hazard ratio (HR) for dementia patients is still controversial. Some studies have supported the association between TBI and dementia, especially for Alzheimer's disease, and our study determined that the HR of dementia patients with and without a history of TBI or repeated TBI (RTBI). We determined the HR for dementia patients with a diagnosis of TBI (n = 12931) and a comparative cohort with age- and gender-matched controls (n = 51724) during 2004-2005, using Taiwan's National Health Insurance Research Database. The adjusted HR (HR = 3.21) for dementia patients with TBI showed that they were more likely to develop dementia than the comparison cohort. The HR for dementia patients with RTBI was increased to 3.62. The results of this large-scale study suggested that TBI increases dementia risk. Future studies using animal models and epidemiological databases could elucidate medical and biological mechanisms linking TBI and the development of dementia.

Obstetric Care Consensus No. 5: Severe Maternal Morbidity: Screening and Review.

This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review.

Severe maternal morbidity: screening and review

This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review.

Regional adaptation of collagen in skeletal muscle to repeated bouts of strenuous eccentric exercise.

This study investigated the injured region-specific alterations of factors related to the "repeated bout effect" (RBE), i.e., when the first bout of eccentric exercise generates resistance to injuries from the second bout of the same exercise. Wistar rats were divided into single injury (SI) and repeated injury (RI) groups. The right gastrocnemius muscle was subjected to a bout of eccentric contractions (ECs) at the age of 14weeks in the SI group and 10 and 14weeks in the RI group. The number of injured fibers after the last bout of ECs was lower in RI than in SI. In the SI group, injured fibers after ECs were mainly located in the superficial region of muscle and expressed myosin heavy chain (MHC) IIx and IIb. Prior to the second bout of ECs, the fiber-type composition in the RI group showed decreased MHC IIx and IIb fibers and increased MHC IIa fibers compared with those in the SI group. However, most regenerating fibers showed either MHC IIx or IIb expression. Heat shock protein 72 and total collagen contents in whole muscle were higher in the RI group than in the SI group; however, only the collagen expression in the RI group was more intense than that in the SI group in the superficial region of muscle. These findings suggest that increased collagen may play a more important role in the injured region of muscle than the other factors in RBE.

Neonatal Tissue Damage Promotes Spike Timing-Dependent Synaptic Long-Term Potentiation in Adult Spinal Projection Neurons.

Mounting evidence from both humans and rodents suggests that tissue damage during the neonatal period can "prime" developing nociceptive pathways such that a subsequent injury during adulthood causes an exacerbated degree of pain hypersensitivity. However, the cellular and molecular mechanisms that underlie this priming effect remain poorly understood. Here, we demonstrate that neonatal surgical injury relaxes the timing rules governing long-term potentiation (LTP) at mouse primary afferent synapses onto mature lamina I projection neurons, which serve as a major output of the spinal nociceptive network and are essential for pain perception. In addition, whereas LTP in naive mice was only observed if the presynaptic input preceded postsynaptic firing, early tissue injury removed this temporal requirement and LTP was observed regardless of the order in which the inputs were activated. Neonatal tissue damage also reduced the dependence of spike-timing-dependent LTP on NMDAR activation and unmasked a novel contribution of Ca(2+)-permeable AMPARs. These results suggest for the first time that transient tissue damage during early life creates a more permissive environment for the production of LTP within adult spinal nociceptive circuits. This persistent metaplasticity may promote the excessive amplification of ascending nociceptive transmission to the mature brain and thereby facilitate the generation of chronic pain after injury, thus representing a novel potential mechanism by which early trauma can prime adult pain pathways in the CNS. Tissue damage during early life can "prime" developing nociceptive pathways in the CNS, leading to greater pain severity after repeat injury via mechanisms that remain poorly understood. Here, we demonstrate that neonatal surgical injury widens the timing window during which correlated presynaptic and postsynaptic activity can evoke long-term potentiation (LTP) at sensory synapses onto adult lamina I projection neurons, which serve as a major output of the spinal nociceptive circuit and are essential for pain perception. This persistent increase in the likelihood of LTP induction after neonatal injury is predicted to favor the excessive amplification of ascending nociceptive transmission to the mature brain in response to subsequent injury and thereby exacerbate chronic pain.

Salubrinal reduces oxidative stress, neuroinflammation and impulsive-like behavior in a rodent model of traumatic brain injury

Traumatic brain injury (TBI) is the leading cause of trauma related morbidity in the developed world. TBI has been shown to trigger secondary injury cascades including endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation. The link between secondary injury cascades and behavioral outcome following TBI is poorly understood warranting further investigation. Using our validated rodent blast TBI model, we examined the interaction of secondary injury cascades following single injury and how these interactions may contribute to impulsive-like behavior after a clinically relevant repetitive TBI paradigm. We targeted these secondary pathways acutely following single injury with the cellular stress modulator, salubrinal (SAL). We examined the neuroprotective effects of SAL administration on significantly reducing ER stress: janus-N-terminal kinase (JNK) phosphorylation and C/EBP homology protein (CHOP), oxidative stress: superoxide and carbonyls, and neuroinflammation: nuclear factor kappa beta (NFκB) activity, inducible nitric oxide synthase (iNOS) protein expression, and pro-inflammatory cytokines at 24h post-TBI. We then used the more clinically relevant repeat injury paradigm and observed elevated NFκB and iNOS activity. These injury cascades were associated with impulsive-like behavior measured on the elevated plus maze. SAL administration attenuated secondary iNOS activity at 72h following repetitive TBI, and most importantly prevented impulsive-like behavior. Overall, these results suggest a link between secondary injury cascades and impulsive-like behavior that can be modulated by SAL administration.

Distal Radius Fracture in Athletes

Sports-related distal radius fractures (SRDRF) represent 12.5% of all fractures affecting the upper extremity. This type of fracture occurs more frequently in males (76%) than in females (24%), with an average age of presentation of 24.5 years. In the pediatric population, the peak incidence for sports injuries is between 11 and 17 years. High-impact sports, such as football, basketball, and soccer carry an especially high risk for this type of injury. However, because of the wide variety of sport disciplines and different characteristics in demand, velocity, energy, and use of the upper extremities, there is no uniform pattern of SRDRF. The general principles for diagnosis and treatment of distal radius fractures in athletes, for the most part, follow those of the general population. However, unique aspects of the clinical approach to SRDRF in the athlete frequently require additional radiographic views and the common need for advanced imaging such as computer tomography scans and magnetic resonance imaging. Athletes constitute a special patient population. Elite athletes are highly motivated to return to competition as soon as possible, frequently being willing to accept the risk of poor healing or repeat injury The treating physician may be subjected to pressure to prematurely end immobilization, reduce recovery time, and even remove plates or alter therapy based on competition requirements. These influences should be mitigated in favor of the long-term benefit for the patient.

Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial–mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation

Smooth muscle metaplasia (SMM) and fibrotic tissues are frequently seen in endometriotic lesions, yet the mechanisms underlying their formation are poorly understood. In this study, we investigated the roles of activated platelets in driving epithelial–mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) in endometriosis. Through in vitro experimentations, we found that activated platelets, through the release of TGF-β1 and the induction of TGF-β/Smad signaling pathway, promoted EMT and FMT in endometriosis, resulting in increased cell contractility, collagen production, and ultimately to fibrosis. TGF-β blockade reversed these processes. Prolonged exposure of endometriotic stromal cells to activated platelets induced increased expression of α-SMA as well as markers of differentiated smooth muscle cells. Consequently, endometriotic lesions and their microenvironment contain all the necessary molecular machinery to promote SMM and fibrogenesis. Our results suggest that endometriotic lesions are wounds that undergo repeated injury and healing, highlighting the importance of platelets in the development of endometriosis.