Home-Based Transcranial Direct Current Stimulation in Primary Progressive Aphasia: A Pilot Study.

BACKGROUND: This study aims to determine (a) if home-based anodal transcranial direct current stimulation (a-tDCS) delivered to the left supramarginal gyrus (SMG) coupled with verbal short-term memory/working memory (vSTM/WM) treatment ("RAM", short for "Repeat After Me") is more effective than sham-tDCS in improving vSTM/WM in patients with primary progressive aphasia (PPA), and (b) whether tDCS effects generalize to other language and cognitive abilities. METHODS: Seven PPA participants received home-based a-tDCS and sham-tDCS coupled with RAM treatment in separate conditions in a double-blind design. The treatment task required participants to repeat word spans comprising semantically and phonologically unrelated words in the same and reverse order. The evaluation of treatment effects was carried out using the same tasks as in the treatment but with different items (near-transfer effects) and tasks that were not directly related to the treatment (far-transfer effects). RESULTS: A-tDCS showed (a) a significant effect in improving vSTM abilities, measured by word span backward, and (b) a generalization of this effect to other language abilities, namely, spelling (both real words and pseudowords) and learning (retention and delayed recall). CONCLUSIONS: These preliminary results indicate that vSTM/WM intervention can improve performance in trained vSTM/WM tasks in patients with PPA, especially when augmented with home-based tDCS over the left SMG.

Long wavelength light exposure reduces systemic inflammation coagulopathy, and acute organ injury following polytrauma in mice.

BACKGROUND: Evidence suggests that variation in light exposure strongly influences the dynamic of inflammation, coagulation, and the immune system. Polytrauma induces systemic inflammation that can lead to end-organ injury. Here, we hypothesize that alterations in light exposure influence post-trauma inflammation, coagulopathy, and end-organ injury. METHODS: Study Type: Original Research Article. Level of Evidence: Basic Science (Level IV).C57BL/6 mice underwent a validated polytrauma and hemorrhage model performed following 72 hours of exposure to red (617 nm, 1,700lux), blue (321 nm, 1,700lux), and fluorescent white light (300lux) (n = 6-8/group). The animals were sacrificed at 6 h post-trauma. Plasma samples were evaluated and compared for pro-inflammatory cytokine expression levels, coagulation parameters, markers of liver and renal injury, and histological changes (Carstairs staining). One-way ANOVA statistical tests were applied to compare study groups. RESULTS: Pre-exposure to long-wavelength red light significantly reduced the inflammatory response at 6 hours post-polytrauma compared to blue and ambient light, as evidenced by decreased levels of IL-6, MCP-1 (both p < 0.001), liver injury markers (ALT, p < 0.05), and kidney injury markers (cystatin C, p < 0.01). Additionally, Carstairs staining of organ tissues revealed milder histological changes in the red light-exposed group, indicating reduced end-organ damage. Furthermore, PT was significantly lower (p < 0.001) and fibrinogen levels were better maintained (p < 0.01) in the red light-exposed mice compared to those exposed to blue and ambient light. CONCLUSION: Prophylactic light exposure can be optimized to reduce systemic inflammation, coagulopathy and minimize acute organ injury following polytrauma. Understanding the mechanisms by which light exposure attenuates inflammation may provide a novel strategy to reducing trauma related morbidity.

The more things change the more they stay the same: Factors influencing emergency medicine residency selection in the virtual era.

Background: Interviews for emergency medicine (EM) residency positions largely transitioned to a virtual-only format in 2020-2021. The impact of virtual interview factors on applicants' rank of programs is unknown. Objective: We sought to assess the impact of modifiable factors in virtual interviews on applicants' rank of EM residency programs. Methods: We conducted a cross-sectional mixed-methods survey of students applying to at least one of seven study authors' EM residency programs in the United States during the 2020-2021 application cycle. The survey was developed using an interactive Delphi process and piloted prior to implementation. The survey was administered from May to June 2021 with up to four email reminders. Quantitative analysis included descriptive statistics. Three authors performed a thematic qualitative analysis of free-text responses. Results: A total of 664 of 2281 (29.1%) students completed the survey, including 335 (50.5%) male, 316 (47.7%) female, and six (0.9%) nonbinary. A total of 143 (21.6%) respondents identified as underrepresented in medicine and 84 (12.7%) identified as LGBTQIA+. Respondents participated in a median of 14 interviews and ranked a median of 14 programs. Most respondents (335, 50.6%) preferred a choice of in-person or virtual, while 183 (27.6%) preferred all in-person, and 144 (21.8%) preferred all virtual. The program website and interview social were the most important factors influencing respondent ranking. Qualitative analysis revealed several positive aspects of virtual interviews including logistical ease and comfort. Negative aspects include technical issues, perceived interview hoarding, and barriers to applicant assessment and performance. Demonstrated effort by the program, effective information delivery, communication of resident culture, and a well-implemented interview day positively influenced respondents' rank of programs. Conclusions: This study identified characteristics of the virtual interview format that impact applicants' rank of programs. These results can inform future recruitment practices.

MACROPHAGE SWITCHING: POLARIZATION AND MOBILIZATION AFTER TRAUMA.

ABSTRACT: Introduction: Trauma alters the immune response in numerous ways, affecting both the innate and adaptive responses. Macrophages play an important role in inflammation and wound healing following injury. We hypothesize that macrophages mobilize from the circulation to the site of injury and secondary sites after trauma, with a transition from proinflammatory (M1) shortly after trauma to anti-inflammatory (M2) at later time points. Methods: C57Bl6 mice (n = 6/group) underwent a polytrauma model using cardiac puncture/hemorrhage, pseudofemoral fracture, and liver crush injury. The animals were killed at several time points: uninjured, 24 h, and 7 days. Peripheral blood mononuclear cells, spleen, liver nonparenchymal cells, and lung were harvested, processed, and stained for flow cytometry. Macrophages were identified as CD68 + ; M1 macrophages were identified as iNOS + ; M2 macrophages as arginase 1 + . Results: We saw a slight presence of M1 macrophages at baseline in peripheral blood mononuclear cells (6.6%), with no significant change at 24 h and 7 days after polytrauma. In contrast, the spleen has a larger population of M1 macrophages at baseline (27.7%), with levels decreasing at 24 h and 7 days after trauma (20.6% and 12.6%, respectively). A similar trend is seen in the lung where at baseline 14.9% of CD68 + macrophages are M1, with subsequent continual decrease reaching 8.7% at 24 h and 4.4% at 7 days after polytrauma. M1 macrophages in the liver represent 14.3% of CD68 + population in the liver nonparenchymal cells at baseline. This percentage increases to 20.8% after trauma and decreases at 7 days after polytrauma (13.4%). There are few M2 macrophages in circulating peripheral blood mononuclear cells and in spleen at baseline and after trauma. The percentage of M2 macrophages in the lungs remains constant after trauma (7.2% at 24 h and 9.2% at 7 days). In contrast, a large proportion of M2 macrophages are seen in the liver at baseline (36.0%). This percentage trends upward and reaches 45.6% acutely after trauma and drops to 21.4% at 7 days. The phenotypic changes in macrophages seen in the lungs did not correlate with a functional change in the ability of the macrophages to perform oxidative burst, with an increase from 2.0% at baseline to 22.1% at 7 days after polytrauma ( P = 0.0258). Conclusion: Macrophage phenotypic changes after polytrauma are noted, especially with a decrease in the lung M1 phenotype and a short-term increase in the M2 phenotype in the liver. However, macrophage function as measured by oxidative burst increased over the time course of trauma, which may signify a change in subset polarization after injury not captured by the typical macrophage phenotypes.

EFFECT OF IRRIGATION FLUID COMPOSITION ON HEMOSTASIS IN MOUSE BLEEDING MODELS.

ABSTRACT: Introduction: Intraoperative irrigation, usually with normal saline (NS), aids in bleeding identification and management. We investigated the effect of different irrigation fluids, with additives, on hemostasis using two bleeding models. Methods: C57BL/6 J mice were subjected to a tail bleed model or uncontrolled abdominal hemorrhage via liver laceration followed by abdominal cavity irrigation. We compared NS, lactated Ringer's (LR), and PlasmaLyte. We examined NS and LR at different temperatures. Normal saline or LR with calcium (Ca 2+ ) or tranexamic acid (TXA) was studied. Results: Compared with room temperature (RT), increasing the temperature of the irrigation fluid to 37°C and 42°C reduced tail vein bleeding times substantially in both NS and LR (all P < 0.001), with no significant differences between the two fluids. At RT, LR, but not PlasmaLyte, substantially reduced bleeding times in comparison to NS ( P < 0.0001). Liver injury blood loss was lower with LR ( P < 0.01). Normal saline supplemented with 2.7 mEq/L of Ca 2+ decreased bleeding time and blood loss volume ( P < 0.001 and P < 0.01, respectively) to similar levels as LR. Normal saline with 150 mg/mL of TXA markedly reduced bleeding time ( P < 0.0001), and NS with 62.5 mg/mL TXA decreased blood loss ( P < 0.01). Conclusion: Whereas Ca 2+ - and TXA-supplemented NS reduced bleeding, LR remained superior to all irrigation fluid compositions. As LR contains Ca 2+ , and Ca 2+ -supplemented NS mirrored LR in response, Ca 2+ presence in the irrigation fluid seems key to improving solution's hemostatic ability. Because warming the fluids normalized the choice of agents, the data also suggest that Ca 2+ -containing fluids such as LR may be more suitable for hemostasis when used at RT.

Bilateral Central Retinal Vein Occlusion as a First Presentation of Multiple Myeloma: A Case Report.

INTRODUCTION: Acute presentation of multiple myeloma in the emergency department (ED) is an uncommon yet life-threatening clinical entity. CASE REPORT: A 42-year-old male presented to the ED with severe generalized fatigue and vision changes most notable in his left eye. Bilateral central retinal vein occlusion (CRVO) was diagnosed on dilated fundus exam in the ED. CONCLUSION: The most common cause of CRVO in adults over age 50 is vascular disease, but in younger adults, conditions of systemic inflammation or hyperviscosity must be considered. Diagnosis of CRVO requires emergent ophthalmology consultation and further treatment with phototherapy, steroids, and potentially anti-vascular endothelial growth factor. Ultimately, patients require hematology/oncology and ongoing management of acute hyperviscosity syndrome. We present this case to increase awareness surrounding this diagnosis among emergency physicians. Multiple myeloma should be considered in young patients who present to the ED with bilateral CRVO, acute renal failure, and symptomatic anemia.

Effects of Brief Mental Skills Training on Emergency Medicine Residents' Stress Response During a Simulated Resuscitation: A Prospective Randomized Trial.

BACKGROUND: Acute stress impairs physician decision-making and clinical performance in resuscitations. Mental skills training, a component of the multistep, cognitive-behavioral technique of stress inoculation, modulates stress response in high-performance fields. OBJECTIVE: We assessed the effects of mental skills training on emergency medicine (EM) residents' stress response in simulated resuscitations as well as residents' perceptions of this intervention. METHODS: In this prospective, educational intervention trial, postgraduate year-2 EM residents in seven Chicago-area programs were randomly assigned to receive either stress inoculation training or not. One month prior to assessment, the intervention group received didactic training on the "Breathe, Talk, See, Focus" mental performance tool. A standardized, case-based simulation was used for assessment. We measured subjective stress response using the six-item short form of the Spielberger State-Trait Anxiety Inventory (STAI-6). Objective stress response was measured through heart rate (HR) and heart rate variability (HRV) monitoring. We measured subjects' perceptions of the training via survey. RESULTS: Of 92 eligible residents, 61 participated (25 intervention; 36 control). There were no significant differences in mean pre-/post-case STAI-6 scores (-1.7 intervention, 0.4 control; p = 0.38) or mean HRV (-3.8 milliseconds [ms] intervention, -3.8 ms control; p = 0.58). Post-assessment surveys indicated that residents found this training relevant and important. CONCLUSION: There was no difference in subjective or objective stress measures of EM resident stress response after a didactic, mental performance training session, although residents did value the training. More extensive or longitudinal stress inoculation curricula may provide benefit.

A Positive Depression Screen Is Associated with Emergency Medicine Resident Burnout and Is not Affected by the Implementation of a Wellness Curriculum.

INTRODUCTION: While burnout is occupation-specific, depression affects individuals comprehensively. Research on interventions for depression in emergency medicine (EM) residents is limited. OBJECTIVES: We sought to obtain longitudinal data on positive depression screens in EM residents, assess their association with burnout, and determine whether implementation of a wellness curriculum affected the rate of positive screens. METHODS: In February 2017, we administered the Maslach Burnout Inventory and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire two-question depression screen at 10 EM residencies. At five intervention sites, a year-long wellness curriculum was then introduced while five control sites agreed not to introduce new wellness initiatives during the study period. Study instruments were re-administered in August 2017 and February 2018. RESULTS: Of 382 residents, 285 participated in February 2017; 40% screened positive for depression. In August 2017, 247/386 residents participated; 27.9% screened positive for depression. In February 2018, 228/386 residents participated; 36.2% screened positive. A positive depression screen was associated with higher burnout. There were similar rates of positive screens at the intervention and control sites. CONCLUSION: Rates of positive depression screens in EM residents ranged between 27.9% and 40%. Residents with a positive screen reported higher levels of burnout. Rates of a positive screen were unaffected by introduction of a wellness curriculum.

Platelet HMGB1 in Platelet-Rich Plasma (PRP) promotes tendon wound healing.

Platelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a chemoattractant that can recruit stem cells to the wound area to enhance healing of injured tissues; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP on tendon healing using PLT HMGB1 knockout (KO) and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1-KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1-KO mice showed better healing with PRP from HMGB1-KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1-KO mice. Thus, PLT HMGB1 within PRP plays an important role in tendon wound healing by decreasing inflammation, increasing local HMGB1 levels, and recruiting stem cells to the wound area in the tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may depend on PLT HMGB1 within PRP preparations.

Emergency Medicine Residents With Higher Levels of Debt Are Less Likely to Choose Academic Jobs, but There Is a Difference by Gender.

OBJECTIVES: We sought to answer the following question: Does educational debt burden affect decisions by emergency medicine residents about whether to pursue academic versus community medicine jobs directly after residency? METHODS: In this observational study, graduating residents across eight emergency medicine residencies were surveyed concurrent with their in-training examinations over 2 years to assess levels of educational debt and demographic information. Job types chosen by residents upon graduation were obtained from their respective program directors. The impact of debt on type of job chosen was assessed through multivariate logistic regression with demographic controls and program fixed effects, with additional analysis of observed differences by gender. RESULTS: Information was collected on 159 residents from 14 graduating classes across eight programs representing six different states. Residents with higher levels of debt had lower odds of choosing an academic fellowship or faculty position upon graduation (odds ratio [OR] = 0.77, confidence interval [CI] = 0.60 to 0.98). On further analysis, higher debt predicted lower odds of choosing an academic position for men (OR = 0.59, CI = 0.41 to 0.82), but not for women (OR = 1.05, CI = 0.63 to 1.76). CONCLUSIONS: When male emergency medicine residents have higher levels of debt, they are significantly less likely to pursue an academic fellowship or faculty position after residency. This may not be the case for female residents. Results may reflect differences in the factors that affect men and women's decisions about jobs after residency, which merits further study.

Characterization of the structure, vascularity, and stem/progenitor cell populations in porcine Achilles tendon (PAT).

This study aimed to characterize porcine Achilles tendon (PAT) in terms of its structural components, vascularity, and resident tendon cells. We found that PAT is composed of a paratenon sheath, a core of fascicles, and an endotenon/interfascicular matrix (IFM) that encases the fascicle bundles. We analyzed each of these three tendon components structurally using tissue sections and by isolating cells from each component and analyzing in vitro. Many blood vessel-like tissues were present in the paratenon and IFM but not in fascicles, and the vessels in the paratenon and IFM appeared to be inter-connected. Cells isolated from the paratenon and IFM displayed characteristics of vascular stem/progenitor cells expressing the markers CD105, CD31, with α-smooth muscle actin (α-SMA) localized surrounding blood vessels. The isolated cells from paratenon and IFM also harbored abundant stem/progenitor cells as evidenced by their ability to form colonies and express stem cell markers including CD73 and CD146. Furthermore, we demonstrate that both paratenon and IFM-isolated cells were capable of undergoing multi-differentiation. In addition, both paratenon and IFM cells expressed elastin, osteocalcin, tubulin polymerization promoting protein (TPPP), and collagen IV, whereas fascicle cells expressed none of these markers, except collagen I. The neurotransmitter substance P (SP) was also found in the paratenon and IFM-localized surrounding blood vessels. The findings of this study will help us to better understand the vascular and cellular mechanisms of tendon homeostasis, injury, healing, and regeneration.

Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo.

To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon.

Synthesis of non-nucleoside anti-viral cyclopropylcarboxacyl hydrazones and initial anti-HSV-1 structure-activity relationship studies.

The synthesis of a lead anti-viral cyclopropyl carboxy acyl hydrazone 4F17 (5) and three sequential arrays of structural analogues along with the initial assessment and optimization of the antiviral pharmacophore against the herpes simplex virus type 1 (HSV-1) are reported.

The Implementation of a National Multifaceted Emergency Medicine Resident Wellness Curriculum Is Not Associated With Changes in Burnout.

BACKGROUND: The Accreditation Council for Graduate Medical Education Common Program Requirements effective 2017 state that programs and sponsoring institutions have the same responsibility to address well-being as they do other aspects of resident competence. OBJECTIVES: The authors sought to determine if the implementation of a multifaceted wellness curriculum improved resident burnout as measured by the Maslach Burnout Inventory (MBI). METHODS: We performed a multicenter educational interventional trial at 10 emergency medicine (EM) residencies. In February 2017, we administered the MBI at all sites. A year-long wellness curriculum was then introduced at five intervention sites while five control sites agreed not to introduce new wellness initiatives during the study period. The MBI was readministered in August 2017 and February 2018. RESULTS: Of 523 potential respondents, 437 (83.5%) completed at least one MBI assessment. When burnout was assessed as a continuous variable, there was a statistically significant difference in the depersonalization component favoring the control sites at the baseline and final survey administrations. There was also a higher mean personal accomplishment score at the control sites at the second survey administration. However, when assessed as a dichotomous variable, there were no differences in global burnout between the groups at any survey administration and burnout scores did not change over time for either control or intervention sites. CONCLUSIONS: In this national study of EM residents, MBI scores remained stable over time and the introduction of a multifaceted wellness curriculum was not associated with changes in global burnout scores.

The Correlation Between Emergency Medicine Residents' Grit and Achievement.

BACKGROUND: Early identification of emergency medicine (EM) residents who struggle with educational attainment is difficult. In-training examination (ITE) scores predict success on the American Board of Emergency Medicine (ABEM) Qualifying Examination; however, results are not available until late in the academic year. The noncognitive trait "grit," defined as "perseverance and passion for long-term goals," predicts achievement in high school graduation rates, undergraduate GPA, and gross anatomy. Grit-S is a validated eight-question scale scored 1 to 5; the average of responses represents a person's grit. Our objective was to determine the correlation between EM resident Grit-S scores and achievement, as measured by MCAT percentiles, ITE scores, and remediation rates. STUDY DESIGN AND METHODS: This was a 1-year prospective, multicenter trial involving ten EM residencies from 2017 to 2018. Subjects were PGY-1 to -4 EM residents. Grit-S scores, MCAT percentile, remediation rates, ITE scores, and the ITE score's prediction of passing the ABEM Qualifying Examination were collected. Correlation coefficients were computed to assess the relationship between residents' grit and achievement. RESULTS: A total 385 of 434 (88.7%) residents participated who completed the Grit-S as part of a larger study. The mean Grit-S score was 3.62. Grit positively correlated with the predicted likelihood of passing the ABEM Qualifying Examination (r = 0.134, n = 382, p = 0.025). There was no correlation between grit and remediation (r = -0.04, n = 378, p = 0.46) or grit and MCAT percentiles (r =- 0.08, n = 262, p = 0.22). CONCLUSIONS: The positive correlation between Grit-S scores and percent likelihood of passing the ABEM Qualifying Examination demonstrates grit's potential to assist residency leadership in early identification of residents who may attain a lower ITE score.

Standardized Letters of Concern and Remediation Contracts: Templates for Program Directors.

BACKGROUND: Remediation of the struggling resident is a universal phenomenon, and the majority of program directors will remediate at least 1 resident during their tenure. OBJECTIVE: The goal of this project was to create a standardized template for program directors to use at all stages of remediation. METHODS: Between 2017 and 2018, the Council of Residency Directors in Emergency Medicine (CORD-EM) Remediation Committee searched for best practices in the medical literature and compiled a survey that was e-mailed to the CORD-EM listserv. After reviewing all information, a standardized remediation contract was created, reviewed by legal counsel, and distributed to members. RESULTS: Forty-two percent (110 of 263) of program directors or assistant program directors on the CORD-EM listserv answered the initial survey and provided guidance on current remediation practices. The committee created formal and informal standard remediation contracts as both fillable templates and alterable documents. These were reviewed by CORD-EM general legal counsel and approved by the CORD-EM Board of Directors for distribution. The project took approximately 20 hours to complete over 8 months and involved a cost of $480 for legal fees. CONCLUSIONS: With program director input and legal counsel review, the CORD-EM Remediation Committee produced standardized remediation contracts, which can be used by all emergency medicine programs after comparison to local institutional policy and local legal review. This process was feasible and can be replicated by other specialties.

An Emergency Medicine Remediation Consult Service: Access to Expert Remediation Advice and Resources.

Resident remediation is a complex and common issue in emergency medicine programs and requires a specific knowledge base. The Remediation Task Force (RTF) of the Council of Residency Directors in Emergency Medicine (CORD-EM) was created to identify remediation best practices and to develop tools for program directors. Initially housed on a Wiki page, and now located within the CORD-EM website, the RTF provides resources including accepted universal language for documentation and sample remediation plans. The RTF also created a remediation consult service composed of experienced educators to provide real-time structured feedback and advice to submitted remediation scenarios with consultation outcomes and conclusions uploaded to the website. CORD-EM members now have easy access to online resources and expert advice for remediation queries through the consult service. The combination of online resources and access to real-time expert advice is an innovative approach to improving resident remediation and recognizing best practices.

Selectively activated PRP exerts differential effects on tendon stem/progenitor cells and tendon healing.

To understand the variable efficacy with platelet rich plasma (PRP) treatments for tendon injury, we determined the differential effects of proteinase-activated receptor (PAR)1- or PAR4-activated PRP (PAR1-PRP, PAR4-PRP) from humans on human patellar tendon stem/progenitor cells (TSCs) and tendon healing. We show that PAR1-PRP released VEGF, whereas PAR4-PRP released endostatin. Treatment of TSCs with PAR1-PRP increased collagen I expression and matrix metalloproteinase-1 (MMP-1), but cells treated with PAR4-PRP increased less collagen I and higher MMP-2 expression. The wound area treated with PAR4-PRP formed tendon-like tissues with well-organized collagen fibers and fewer blood vessels, while PAR1-PRP treatment resulted in the formation of blood vessels and unhealed tissues. These findings indicate that differential activation of PRP leads to different effects on TSCs and tendon healing. We suggest that based on acute or chronic type of tendon injury, selective activation of PRP should be applied in clinics in order to treat injured tendons successfully.