Racial Hate at the Intersection of Online and Offline Worlds: The Joint Impact of Online and Offline Racism on the Mental Health of Racially Minoritized Individuals.

With the everyday influence of social media and online platforms, racially minoritized individuals face the risk of experiencing racial discrimination in both offline and online contexts. Yet, there is scant research on how online and offline racism could jointly impact the mental health of racially minoritized individuals. Thus, the study examined online racism as a moderator in the link between offline racism and mental health issues. Using data from 651 racially minoritized emerging adults (Mage = 22.15, SD = 3.39), a moderation analysis was conducted using the PROCESS macro with bias-corrected bootstrapping (10,000 resamples). Experiencing more offline racism was significantly associated with greater mental health issues. Online racism was a significant moderator in the link between offline racism and mental health issues. The link between offline racism and mental health issues was not significant at low levels of online racism. However, the link was significant and strengthened at mean to high levels of online racism. The results suggest complex interactions in understanding the compounding impact of online and offline racism on mental health costs among racially minoritized individuals. Implications for future research on understanding the interplay between online and offline racism are discussed.

Analysis of Personalized Interbody Implants in the Surgical Treatment of Adult Spinal Deformity.

STUDY DESIGN: Multicenter cohort. OBJECTIVES: A report from the International Spine Study Group (ISSG) noted that surgeons failed to achieve alignment goals in nearly two-thirds of 266 complex adult deformity surgery (CADS) cases. We assess whether personalized interbody spacers are associated with improved rates of achieving goal alignment following adult spinal deformity (ASD) surgery. METHODS: ASD patients were included if their surgery utilized 3D-printed personalized interbody spacer(s) and they met ISSG CADS inclusion criteria. Planned alignment was personalized by the surgeon during interbody planning. Planned vs achieved alignment was assessed and compared with the ISSG CADS series that used stock interbodies. RESULTS: For 65 patients with personalized interbodies, 62% were women, mean age was 70.3 years (SD = 8.3), mean instrumented levels was 9.9 (SD = 4.1), and the mean number of personalized interbodies per patient was 2.2 (SD = .8). Segmental alignment was achieved close to plan for levels with personalized interbodies, with mean difference between goal and achieved as follows: intervertebral lordosis = .9° (SD = 5.2°), intervertebral coronal angle = .1° (SD = 4.7°), and posterior disc height = -0.1 mm (SD = 2.3 mm). Achieved pelvic incidence-to-lumbar lordosis mismatch (PI-LL) correlated significantly with goal PI-LL (r = .668, P < .001). Compared with the ISSG CADS cohort, utilization of personalized interbodies resulted in significant improvement in achieving PI-LL <5° of plan (P = .046) and showed a significant reduction in cases with PI-LL >15° of plan (P = .012). CONCLUSIONS: This study supports use of personalized interbodies as a means of better achieving goal segmental sagittal and coronal alignment and significantly improving achievement of goal PI-LL compared with stock devices.

Scoping review of the association of plant-based diet quality with health outcomes.

Introduction: The association of plant-based dietary patterns with health outcomes has traditionally been assessed without considering nutritional value. The plant-based dietary index (PDI), first published in 2016, overcomes this limitation with both a healthful PDI (hPDI) and an unhealthful PDI (uPDI), based on the quality of plant foods consumed plus the frequency of animal foods. We sought to summarize the breadth of research using the hPDI and uPDI to gain insight into how the quality of plant-based dietary patterns might be associated with health outcomes. Methods: Scoping review of studies that used the PDI, hPDI, or uPDI to report associations with health outcomes. Multiple databases were searched from 2010 through April 2023 with 2 authors independently assessing eligibility and extracting data. In addition to assessing the association of the indices to health outcomes, we determined the frequency of concordant or discordant findings for hPDI versus PDI and for hPDI versus uPDI. Results: We included 95 articles (54% longitudinal, 37% cross-sectional, and 9% case-control) with a median sample size of 3,646. Higher hPDI levels were associated with favorable health outcomes in 36% of comparisons (most often for obesity, mortality, diabetes, cardiovascular disease, and psychiatric disorders), compared to 25% for the PDI and only 2% for the uPDI. Conversely, higher levels of the uPDI were associated with unfavorable health outcomes in 33% of comparisons, in contrast to under 1% for the hPDI and 2% for the PDI. When the hPDI association to an outcome was discordant with the uPDI or PDI, the significance and directionality always favored the hPDI over the uPDI, and nearly always favored the hPDI over the PDI. Discussion: Dietary indices that account for the quality of plant foods can show health benefits that might be missed by a generic plant-based index. A greater focus on the quality of plant foods could improve nutrition guidelines, raise awareness about the benefits of adding unrefined plant foods to the diet, and empower consumers to make incremental additions of such foods to displace unhealthy foods. We anticipate increasing use of indices that address food quality in future research.

An Overview of Acute Otitis Externa.

Acute otitis externa, cellulitis of the external auditory canal, is most frequently due to bacteria. Patients may present with otalgia, aural fullness, hearing loss, and otorrhea. Its diagnosis is a clinical one. Treatment is focused on analgesia, treating the underlying infection and preventing recurrence.

COVID-19 anti-Asian racism, perceived burdensomeness, thwarted belongingness, and suicidal ideation among Asian American Emerging Adults.

Since the start of the COVID-19 pandemic, there has been a significant surge in COVID-19 related anti-Asian racism and hate crimes. Given the ostracising and dehumanising narrative of COVID-19 related anti-Asian hate, we examined whether COVID-19 anti-Asian racism would be associated with suicidal ideation through increased thwarted belongingness and perceived burdensomeness among Asian American emerging adults. With data from 139 participants (Mage = 23.04), we conducted a path analysis of COVID-19 anti-Asian racism (four items) predicting suicidal ideation (item nine; Patient Health Questionnaire-9) via perceived burdensomeness and thwarted belongingness (Interpersonal Needs Questionnaire). COVID-19 anti-Asian racism significantly predicted suicidal ideation. The indirect effect through perceived burdensomeness was significant but not through thwarted belongingness; greater COVID-19 anti-Asian racism was associated with greater perceived burdensomeness, which in turn was associated with greater suicidal ideation. The significance of perceived burdensomeness was substantiated given the non-significant direct effect. The results suggest that the ongoing COVID-19 anti-Asian racism may be an alarming risk factor for suicidal ideation for Asian American emerging adults.

Gendered racial microaggressions, internalized racism, and suicidal ideation among emerging adult Asian American women.

BACKGROUND: Despite suicide being the leading cause of death among emerging adult Asian American women (AAW), little is known about the risk factors. AIM: We tested whether gendered racial microaggressions stress (GRMS) would be associated with AAW's suicidal ideation, and whether internalized racism (self-negativity, IRSN; weakness stereotypes, IRWS; and appearance bias, IRAB) would exacerbate this link based on self-devaluating implications of internalized racism. METHOD: Using a sample of 309 AAW (Mage = 20.00, SD = 6.26), we conducted a moderated logistic regression with GRMS predicting suicidal ideation (endorsement or no endorsement) and the three internalized racism factors (IRSN, IRWS, and IRAB) as moderators. RESULTS: GRMS significantly predicted suicidal ideation with a threefold increase in the odds of suicidal ideation. Only IRSN significantly exacerbated this link at low to mean levels. CONCLUSION: Gendered racial microaggressions is likely a risk factor for suicidal ideation among AAW, particularly for those who internalize negative images of themselves as Asian individuals.

Racial/ethnic differences in social support and health among Asian American and non-Hispanic White midlife women: Results from the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Although prior research suggests Asian Americans experience physical health advantages relative to other racial/ethnic groups, increasing evidence points to health inequalities within Asian American subgroups. Disparities are especially pronounced among middle-aged Asian American women, who remain an understudied population, despite studies showing that midlife corresponds with distinct social stressors and changes in the availability of protective resources, such as social support. Thus, the purpose of the study was to examine racial/ethnic differences in social support and self-rated health (SRH) among middle-aged women. DESIGN: With data from the Study of Women's Health Across the Nation (SWAN; N = 1258), we used modified Poisson regression models to estimate incidence rate ratios (IRR), examining how social support shaped the risk of fair-to-poor SRH by race/ethnicity. We tested interactions between perceived stress, social support and race/ethnicity to determine whether the stress-buffering role of social support varies by group. RESULTS: Results demonstrate racial/ethnic differences in SRH. Higher levels of social support were linked to higher fair-to-poor SRH among Chinese American women (IRR = 1.24; 95% CI [1.02, 1.52]); while greater social support conferred lower risk among White women. Interaction analyses revealed additional nuances in the stress-buffering effects of social support among Chinese American women, such that the health benefits of social support depended on levels of perceived stress (IRR = 0.75; 95% CI [0.57, 1.00]). CONCLUSIONS: These findings highlight important distinctions in the ways that psychosocial factors shape health across racial/ethnic groups. In particular, this study helps advance our understanding of important subgroup differences in the stress-buffering role of social support for Asian American midlife women. Interventions should focus on identifying sources of social strain among Asian American women that can increase the risk for poor health and identify alternative sources of support that mitigate stressors to improve health.

Witnessing racism against racial minority individuals online and loneliness among White emerging adults: Anti-racism advocacy as a moderator.

Extant literature suggests that racism is associated with difficult emotional reactions and feelings of social disconnect among White individuals. These feelings of social disconnect may be particularly salient in today's digital era in which racism against racial minority individuals is conveniently and frequently witnessed via online platforms. Thus, we examined whether witnessing racism online may be associated with feelings of loneliness among White emerging adults. We also tested whether anti-racism advocacy buffered loneliness given its potential for relationship building and community organizing to promote racial justice and equity. Using data from 227 White emerging adults (Mage = 20.86, SD = 4.82), we conducted a latent moderated structural equation modeling to test individual and institutional anti-racism advocacy as moderators in the link between witnessing racism online (racial victimization of racial minority individuals in online interactions and online content on cultural devaluation/systemic racism against racial minority individuals) and loneliness. Greater exposure to online content on systemic racism and cultural devaluation of racial minority groups significantly predicted greater loneliness. Engagement in individual anti-racism advocacy (mean to high levels) buffered this link. White allies must engage in anti-racism practice to address racism in our society, and our findings advance our understanding of the associated psychosocial costs. Implications for research and practice are discussed.

Congruence and discrepancy in Asian American women's perception and stress appraisal of gendered racial microaggressions: Relationships with depressive symptoms and internalized racism.

Prior research demonstrates significant links between discrimination and mental health by assessing either encounters with or stress appraisal of discrimination. However, research has yet to examine the dynamic interplay between frequency and stress appraisal (e.g., high frequency-low stress appraisal) and their linkage to depressive symptoms. Using a sample of 309 Asian American women (M age = 22.81, SD = 0.26), we used a polynomial regression and response surface analysis to model the congruence and discrepancy between frequency and stress appraisal of gendered racial microaggressions experienced by Asian American women and how they are related to depressive symptoms and internalized racism. The dynamics between frequency and stress in relation to depressive symptoms were further probed at low, mean, and high levels of internalized racism. Greater congruence between frequency and stress was significantly associated with depressive symptoms (medium to large effect) and internalized racism (small effect). A discrepancy between higher frequency and lower stress was significantly associated with greater internalized racism. Further, when looking across levels of internalized racism, greater congruence between frequency and stress was significantly associated with greater depressive symptoms at low and mean levels of internalized racism but not at high levels. Gendered racial microaggressions are associated with adverse mental health outcomes among Asian American women, contributing to greater depressive symptoms and internalized racism. Further consideration should be given toward how internalized racism shapes differences in the perceptions and stress appraisal of gendered racial microaggressions, and subsequent mental health outcomes among Asian American women.

Primary and Revision Anterior Cervical Discectomy and Fusion: A Study of Otolaryngologic Outcomes in a Large Cohort.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: To determine risk factors for postoperative otolaryngologic complications among patients who undergo primary and revision anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Swallowing and voice dysfunction are frequent postoperative complaints after ACDF surgery with a published incidence varying between 1.2% and 60%. A thorough understanding of the incidence and risk factors for these complications is needed. METHODS: Electronic medical records of adults who underwent ACDF with predicted difficult surgical site exposure performed by two-surgeon approach between 2008 and 2018 were reviewed. Patients were categorized by primary or revision ACDF status and by the number of levels addressed during the operation. Associations with postoperative otolaryngologic symptoms were assessed using simple and multivariable logistic regression. RESULTS: Participants included 718 adults with an average age of 55.8 years and 45% female sex. One hundred seventy-five patients (27%) underwent revision ACDF; ACDF status was unidentifiable for 74 patients. Seventy-nine cases (12%) involved one spinal level. New postoperative otolaryngologic symptoms among those who underwent primary and revision ACDF were 12.6% and 10.9% respectively. No evidence was found of an association between postoperative otolaryngologic symptoms and revision ACDF (OR, 0.84 [95% CI, 0.48-1.49]; P  = 0.55), but evidence was found of an association with prior thyroidectomy (aOR, 3.8 [95% CI, 1.53-8.94], P  = 0.0003). Significant evidence was found of increased odds for new postoperative dysphagia with increasing number of surgical levels (aOR, 1.5 [95% CI, 1.09-2.07]; P = 0.01). CONCLUSION: Prior thyroidectomy and number of spinal levels addressed during ACDF were identified as risk factors for postoperative otolaryngologic complications including dysphagia. Revision ACDF was not associated with increased odds of postoperative otolaryngologic symptoms or dysphagia.Level of Evidence: 4.

Effects of an articular cartilage lubrication with a viscosupplement in vitro and in vivo following osteochondral fractures in horses.

OBJECTIVE: To assess whether the combination of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine (HCSG) lubricates articular cartilage in vitro and modulates joint lubrication in vivo. ANIMALS: 16 healthy adult horses. PROCEDURES: The effects of HCSG injections on SF lubricant properties and joint health, immediately after injury and 2 weeks later, were analyzed by use an equine osteochondral fracture model of post-traumatic osteoarthritis (OA). Middle carpal joints of adult horses were randomly assigned to 1 of 4 surgical treatment groups as follows: normal nonsurgical group (n = 8), normal sham-surgical group (8), OA-induced surgical group with HCSG injection (8), or OA-induced surgical group with saline (0.9% NaCl) solution injection (8). Synovial fluid was aspirated periodically and analyzed for boundary lubrication function and lubricant molecules. At 17 days, joints were screened for gross pathological changes. RESULTS: Induction of OA led to an impairment of SF lubrication function and diminished hyaluronan concentration in a time-dependent manner following surgery, with HCSG injection lessening these effects. Certain friction coefficients approached those of unaffected normal equine SF. Induction of OA also caused synovial hemorrhage at 17 days, which was lower in joints treated with HCSG. CONCLUSIONS AND CLINICAL RELEVANCE: After induction of OA, equine SF lubricant function was impaired. Hyaluronan-sodium chondroitin sulfate-N-acetyl-d-glucosamine injection restored lubricant properties at certain time points and reduced pathological joint changes.

Variation in Mutant Prevention Concentrations.

Objectives:Understanding how phenotypic traits vary has been a longstanding goal of evolutionary biologists. When examining antibiotic-resistance in bacteria, it is generally understood that the minimum inhibitory concentration (MIC) has minimal variation specific to each bacterial strain-antibiotic combination. However, there is a less studied resistance trait, the mutant prevention concentration (MPC), which measures the MIC of the most resistant sub-population. Whether and how MPC varies has been poorly understood. Here, we ask a simple, yet important question: How much does the MPC vary, within a single strain-antibiotic association? Using a Staphylococcus species and five antibiotics from five different antibiotic classes-ciprofloxacin, doxycycline, gentamicin, nitrofurantoin, and oxacillin-we examined the frequency of resistance for a wide range of concentrations per antibiotic, and measured the repeatability of the MPC, the lowest amount of antibiotic that would ensure no surviving cells in a 1010 population of bacteria. Results: We found a wide variation within the MPC and distributions that were rarely normal. When antibiotic resistance evolved, the distribution of the MPC changed, with all distributions becoming wider and some multi-modal. Conclusion: Unlike the MIC, there is high variability in the MPC for a given bacterial strain-antibiotic combination.

Identification of early childhood caries in primary care settings.

Early childhood caries (ECC) is the most common chronic disease affecting young children in Canada. ECC may lead to pain and infection, compromised general health, decreased quality of life and increased risk for dental caries in primary and permanent teeth. A multidisciplinary approach to prevent and identify dental disease is recommended by dental and medical national organizations. Young children visit primary care providers at regular intervals from an early age. These encounters provide an ideal opportunity for primary care providers to educate clients about their children's oral health and its importance for general health. We designed an office-based oral health screening guide to help primary care providers identify ECC, a dental referral form to facilitate dental care access and an oral health education resource to raise parental awareness. These resources were reviewed and trialled with a small number of primary care providers.

SMELL-S and SMELL-R: Olfactory tests not influenced by odor-specific insensitivity or prior olfactory experience.

Smell dysfunction is a common and underdiagnosed medical condition that can have serious consequences. It is also an early biomarker of neurodegenerative diseases, including Alzheimer's disease, where olfactory deficits precede detectable memory loss. Clinical tests that evaluate the sense of smell face two major challenges. First, human sensitivity to individual odorants varies significantly, so test results may be unreliable in people with low sensitivity to a test odorant but an otherwise normal sense of smell. Second, prior familiarity with odor stimuli can bias smell test performance. We have developed nonsemantic tests for olfactory sensitivity (SMELL-S) and olfactory resolution (SMELL-R) that use mixtures of odorants that have unfamiliar smells. The tests can be self-administered by healthy individuals with minimal training and show high test-retest reliability. Because SMELL-S uses odor mixtures rather than a single molecule, odor-specific insensitivity is averaged out, and the test accurately distinguished people with normal and dysfunctional smell. SMELL-R is a discrimination test in which the difference between two stimulus mixtures can be altered stepwise. This is an advance over current discrimination tests, which ask subjects to discriminate monomolecular odorants whose difference in odor cannot be quantified. SMELL-R showed significantly less bias in scores between North American and Taiwanese subjects than conventional semantically based smell tests that need to be adapted to different languages and cultures. Based on these proof-of-principle results in healthy individuals, we predict that SMELL-S and SMELL-R will be broadly effective in diagnosing smell dysfunction.

Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration.

BACKGROUND: One potential mechanism for early superficial cartilage wear in normal joints is alteration of the lubricant content and quality of synovial fluid. The purpose of this study was to determine if the concentration and quality of the lubricant, hyaluronan, in synovial fluid: (1) was similar in left and right knees; (2) exhibited similar age-associated trends, whether collected postmortem or antemortem; and (3) varied with age and grade of joint degeneration. METHODS: Human synovial fluid of donors (23-91 years) without osteoarthritis was analyzed for the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, 0.5-1 MDa, and 0.03-0.5 MDa. Similarity of data between left and right knees was assessed by reduced major axis regression, paired t-test, and Bland-Altman analysis. The effect of antemortem versus postmortem collection on biochemical properties was assessed for age-matched samples by unpaired t-test. The relationships between age, joint grade, and each biochemical component were assessed by regression analysis. RESULTS: Joint grade and the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, and 0.5-1 MDa in human synovial fluid showed good agreement between left and right knees and were similar between age-matched patient and cadaver knee joints. There was an age-associated decrease in overall joint grade (-15 %/decade) and concentrations of hyaluronan (-10.5 %/decade), and hyaluronan in the molecular weight ranges of 2.5-7 MDa (-9.4 %/decade), 1-2.5 MDa (-11.3 %/decade), 0.5-1 MDa (-12.5 %/decade), and 0.03-0.5 MDa (-13.0 %/decade). Hyaluronan concentration and quality was more strongly associated with age than with joint grade. CONCLUSIONS: The age-related increase in cartilage wear in non-osteoarthritic joints may be related to the altered hyaluronan content and quality of synovial fluid.

Spirituality and religious coping in African American youth with depressive illness.

The research team completed a secondary data analysis of primary data from a 2 phase depression treatment engagement behavioral trial to assess African American adolescents reported experiences of spiritual and religious coping when dealing with depression. The team utilized data collected from twenty-eight youth who participated in focus groups or individual interviews. Qualitative data were analyzed using thematic techniques for transcript-based analysis to identify the key patterns and elements of the study participants' accounts and to extract 6 primary themes. The main themes are reported in this manuscript and include; "Religion as Treatment Incentive", "Prayer & Agency", "Mixed Emotions", "Doesn't Hurt, Might Help", "Finding Support in the Church", and "Prayer and Church: Barriers to Treatment?" Overall, the data suggested that religion and spirituality play a key role in African American adolescents' experiences of depression. As well, it is surmised that these factors may be important for improving treatment seeking behaviors and reducing racial mental health disparities in this population of youth.

Synovial Fluid Lubricant Properties are Transiently Deficient after Arthroscopic Articular Cartilage Defect Repair with Platelet-Enriched Fibrin Alone and with Mesenchymal Stem Cells.

BACKGROUND: Following various types of naturally-occurring traumatic injury to an articular joint, the lubricating ability of synovial fluid is impaired, with a correlated alteration in the concentration and/or structure of lubricant molecules, hyaluronan and proteoglycan-4. However, the effect of arthroscopic cartilage repair surgery on synovial fluid lubricant function and composition is unknown. HYPOTHESIS: Arthroscopic treatment of full-thickness chondral defects in horses with (1) platelet-enriched fibrin or (2) platelet-enriched fibrin+mesenchymal stem cells leads to equine synovial fluid with impaired lubricant function and hyaluronan and proteoglycan-4 composition. STUDY DESIGN: Controlled Laboratory Study. METHODS: Equine synovial fluid was aspirated from normal joints at a pre-injury state (0 days) and at 10 days and 3 months following fibrin or fibrin+mesenchymal stem cell repair of full thickness chondral defects. Equine synovial fluid samples were analyzed for friction-lowering boundary lubrication of normal articular cartilage (static and kinetic friction coefficients) and concentrations of hyaluronan and proteoglycan-4, as well as molecular weight distribution of hyaluronan. Experimental groups deficient in lubrication function were also tested for the ability of exogenous high-molecular weight hyaluronan to restore lubrication function. RESULTS: Lubrication and biochemical data varied with time after surgery but generally not between repair groups. Relative to pre-injury, kinetic friction was higher (+94%) at 10 days but returned to baseline levels at 3 months while static friction was not altered. Correspondingly, hyaluronan concentration was transiently lower (-64%) and shifted towards lower molecular weight forms, while proteoglycan-4 concentration was increased (+210%) in 10-day samples relative to pre-injury levels. Regression analysis revealed that kinetic friction decreased with increasing total and high molecular weight hyaluronan. Addition of high molecular weight hyaluronan to bring 10-day hyaluronan levels to 2.0mg/ml restored kinetic friction to pre-injury levels. CONCLUSION: Following arthroscopic surgery for cartilage defect repair, synovial fluid lubrication function is transiently impaired, in association with decreased hyaluronan concentration. This functional deficiency in synovial fluid lubrication can be counteracted in vitro by addition of high molecular weight hyaluronan. CLINICAL RELEVANCE: Synovial fluid lubrication is deficient shortly following arthroscopic cartilage repair surgery, and supplementation with high molecular weight hyaluronan may be beneficial.

In vivo efficacy of fresh versus frozen osteochondral allografts in the goat at 6 months is associated with PRG4 secretion.

The long-term efficacy of osteochondral allografts is due to the presence of viable chondrocytes within graft cartilage. Chondrocytes in osteochondral allografts, especially those at the articular surface that normally produce the lubricant proteoglycan-4 (PRG4), are susceptible to storage-associated death. The hypothesis of this study was that the loss of chondrocytes within osteochondral grafts leads to decreased PRG4 secretion, after graft storage and subsequent implant. The objectives were to determine the effect of osteochondral allograft treatment (FROZEN vs. FRESH) on secretion of functional PRG4 after (i) storage, and (ii) 6 months in vivo in adult goats. FROZEN allograft storage reduced PRG4 secretion from cartilage by ∼85% compared to FRESH allograft storage. After 6 months in vivo, the PRG4-secreting function of osteochondral allografts was diminished with prior FROZEN storage by ∼81% versus FRESH allografts and by ∼84% versus non-operated control cartilage. Concomitantly, cellularity at the articular surface in FROZEN allografts was ∼96% lower than FRESH allografts and non-operated cartilage. Thus, the PRG4-secreting function of allografts appears to be maintained in vivo based on its state after storage. PRG4 secretion may be not only a useful marker of allograft performance, but also a biological process protecting the articular surface of grafts following cartilage repair.

Effect of tibial plateau fracture on lubrication function and composition of synovial fluid.

BACKGROUND: Intra-articular fractures may hasten posttraumatic arthritis in patients who are typically too active and too young for joint replacement. Current orthopaedic treatment principles, including recreating anatomic alignment and establishing articular congruity, have not eliminated posttraumatic arthritis. Additional biomechanical and biological factors may contribute to the development of arthritis. The objective of the present study was to evaluate human synovial fluid for friction-lowering function and the concentrations of putative lubricant molecules following tibial plateau fractures. METHODS: Synovial fluid specimens were obtained from the knees of eight patients (twenty-five to fifty-seven years old) with a tibial plateau fracture, with five specimens from the injured knee as plateau fracture synovial fluid and six specimens from the contralateral knee as control synovial fluid. Each specimen was centrifuged to obtain a fluid sample, separated from a cell pellet, for further analysis. For each fluid sample, the start-up (static) and steady-state (kinetic) friction coefficients in the boundary mode of lubrication were determined from a cartilage-on-cartilage biomechanical test of friction. Also, concentrations of the putative lubricants, hyaluronan and proteoglycan-4, as well as total protein, were determined for fluid samples. RESULTS: The group of experimental samples were obtained at a mean (and standard deviation) of 11 ± 9 days after injury from patients with a mean age of 45 ± 13 years. Start-up and kinetic friction coefficients demonstrated similar trends and dependencies. The kinetic friction coefficients for human plateau fracture synovial fluid were approximately 100% higher than those for control human synovial fluid. Hyaluronan concentrations were ninefold lower for plateau fracture synovial fluid compared with the control synovial fluid, whereas proteoglycan-4 concentrations were more than twofold higher in plateau fracture synovial fluid compared with the control synovial fluid. Univariate and multivariate regression analysis indicated that kinetic friction coefficient increased as hyaluronan concentration decreased. CONCLUSIONS: Knees afflicted with a tibial plateau fracture have synovial fluid with decreased lubrication properties in association with a decreased concentration of hyaluronan.

Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation.

Costimulation-deficient dendritic cells (DCs) prevent autoimmune disease in mouse models. However, autoimmune-prone mice and humans fail to control expansion of peripheral autoreactive effector memory T cells (T(EMs)), which resist immunoregulation by costimulation-deficient DCs. In contrast, activation of DC costimulation may be coupled with regulatory capacity. To test whether costimulatory DCs control T(EMs) and attenuate established autoimmune disease, we used RelB-deficient mice, which have multiorgan inflammation, expanded peripheral autoreactive T(EMs), and dysfunctional Foxp3(+) regulatory T cells (Tregs) cells and conventional DCs. T(EMs) were regulated by Foxp3(+) Tregs when costimulated by CD3/CD28-coated beads or wild-type DCs but not DCs deficient in RelB or CD80/CD86. After transfer, RelB and CD80/CD86-sufficient DCs restored tolerance and achieved a long-term cure of autoimmune disease through costimulation of T(EM) and Foxp3(+) Treg IFN-γ production, as well as induction of IDO by host APCs. IDO was required for regulation of T(EMs) and suppression of organ inflammation. Our data challenge the paradigm that costimulation-deficient DCs are required to regulate established autoimmune disease to avoid T(EM) activation and demonstrate cooperative cross-talk between costimulatory DCs, IFN-γ, and IDO-dependent immune regulation. IFN-γ and IDO activity may be good surrogate biomarkers measured against clinical efficacy in trials of autoimmune disease immunoregulation.