Oshkibiimaates Wiidoogakewin: A Partnership between Matawa First Nations Management and St. Joseph's Care Group.

Many Indigenous young people who live in remote northern communities are required to relocate to larger urban centres to pursue their secondary education. These youth have often experienced significant hardships that are exacerbated by the stresses of relocation. When seeking help for these struggles, it can be complicated to navigate complex systems in an unfamiliar city and difficult to engage with services that may not be designed to address these unique needs. The question then becomes: what would happen if those specialized supports were easily accessible and provided in a space where the youth felt safe and valued? A unique program providing holistic and culturally sensitive mental health and substance use services has been developed through a partnership between the Matawa First Nations Management and St. Joseph's Care Group in Thunder Bay, ON. The Oshkibiimaates Wiidoogakewin program has eliminated barriers to accessing service, reduced stigma and met the individual wellness needs of hundreds of students since its inception, with continuous improvements to serve students better. Creativity, flexibility and collaboration are at the heart of this program's success, as well as a shared vision of building a community that helps youth thrive.

COVID-19 and disconnected youth: Lessons and opportunities from OECD countries.

AIMS: This paper highlights how the novel coronavirus pandemic (COVID-19) has amplified economic instability and health risks for disconnected youth and young adults (YYA). We offer a brief review of governmental policy responses in four OECD countries and how they may impact the disconnect YYA within those countries. METHODS: Literature was reviewed utilizing Cochrane Library, ERIC, PsychINFO, PubMed/MEDLINE and Web of Science to outline existing inequities among disconnected YYA and COVID-19 economic and health impacts. Government responses to COVID-19 from four OECD countries were reviewed. Using the social protection model, we highlighted significant policy changes and developments that influence the protection of vulnerable populations and evaluated the potential effect of long-term economic dislocations prompted by the COVID-19 pandemic. RESULTS: Disconnected YYA suffered significant financial and health burdens with no social protection floor in place. Lessons learned prior to and during the pandemic indicate that initiatives aimed at improving health and well-being among vulnerable YYA and their communities must be adequately funded, flexible, and comprehensive. Attempts to connect or reconnect YYA who were disconnected prior to the COVID-19 pandemic will require a re-envisioning of policy. CONCLUSIONS: Globally, governments must invest in social safety net programs that focus on supporting those most at-risk. A concentrated focus on job creation, education and training, and paid work experience, investments in early childhood care and education, housing, health and mental health care is necessary to not only offset the pandemic's effects but also support thriving in the future for YYA.

Folate rescues vitamin B12 depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability.

Clinical vitamin B12 deficiency can result in megaloblastic anemia, which results from the inhibition of DNA synthesis by trapping folate cofactors in the form of 5-methyltetrahydrofolate (5-methylTHF) and subsequent inhibition of de novo thymidylate (dTMP) biosynthesis. In the cytosol, vitamin B12 functions in the remethylation of homocysteine to methionine, which regenerates THF from 5-methylTHF. In the nucleus, THF is required for de novo dTMP biosynthesis, but it is not understood how 5-methylTHF accumulation in the cytosol impairs nuclear dTMP biosynthesis. The impact of vitamin B12 depletion on nuclear de novo dTMP biosynthesis was investigated in methionine synthase-null human fibroblast and nitrous oxide-treated HeLa cell models. The nucleus was the most sensitive cellular compartment to 5-methylTHF accumulation, with levels increasing greater than fourfold. Vitamin B12 depletion decreased de novo dTMP biosynthesis capacity by 5-35%, whereas de novo purine synthesis, which occurs in the cytosol, was not affected. Phosphorylated histone H2AX (γH2AX), a marker of DNA double-strand breaks, was increased in vitamin B12 depletion, and this effect was exacerbated by folate depletion. These studies also revealed that 5-formylTHF, a slow, tight-binding inhibitor of serine hydroxymethyltransferase (SHMT), was enriched in nuclei, accounting for 35% of folate cofactors, explaining previous observations that nuclear SHMT is not a robust source of one-carbons for de novo dTMP biosynthesis. These findings indicate that a nuclear 5-methylTHF trap occurs in vitamin B12 depletion, which suppresses de novo dTMP biosynthesis and causes DNA damage, accounting for the pathophysiology of megaloblastic anemia observed in vitamin B12 and folate deficiency.

Supporting Physical-Behavioral Health Integration Using Medicaid Managed Care Organizations.

This paper describes key findings of two states that sought to integrate physical and behavioral health services by delivering them through one Medicaid managed care contract. The purpose was to explore how managed care organizations (MCOs) could improve physical and behavioral health integration. Promising practices include leveraging data accumulated by MCOs about beneficiaries to support providers and enhanced case management, encouraging MCOs to pay providers for care coordination and care collocation, and offering protections to providers and beneficiaries. Finally, in the absence of a shared vision among key stakeholders regarding how to best promote integrated care, a state can make progress by promoting stakeholder innovation.

Social work intervention for women experiencing early pregnancy loss in the emergency department.

Often referred to as miscarriage, Early Pregnancy Loss (EPL) is the spontaneous death of a fetus experienced within the first 20 weeks of gestation and is the most common complication in pregnancy. Symptoms of an impending EPL are routinely managed in the Emergency Department (ED). EPL can have a substantial impact on women, potentially leading to psychological and emotional health issues and risks to future pregnancies. Despite the high prevalence of EPL, many women suffer in silence due to the common societal belief that EPL are insignificant. Many women experience EPL as an ambiguous loss and are at risk for disenfranchised grief. Compassionate, patient-centred care has been identified by women as an essential and often missing aspect of ED care and can have a profound impact on the overall well-being of women after EPL. Social workers play a critical role in the ED given that they prioritize the psychosocial well-being of patients in a system that is structured to primarily address trauma care. In an effort to reduce the psychological impact and complicated grief reactions of women experiencing EPL, specific recommendations for social work intervention to address the individual needs of women experiencing EPL in the ED are presented. These include acknowledging the loss, providing psychoeducation, honouring the loss, assessing resources, referral and additional information, and building capacity in the ED.

Parent Ratings of Health Insurance Adequacy for Children with Emotional, Behavioral, or Developmental Problems.

OBJECTIVE: Parents of children with special health care needs (CSHCN) report that private insurance is less adequate than public health coverage. Parents of CSHCN with emotional, behavioral, or developmental problems (EBDPs) may perceive private insurance to be especially inadequate due to higher need for a wider array of non-medical services and supports. This study's objective is to assess differences in parent ratings of insurance adequacy for public versus private health coverage between non-CSHCN, CSHCN, and CSHCN with EBDPs. METHODS: This study pooled publicly available data from the 2016 through 2019 National Survey of Children's Health. Multivariable fixed effects logistic regression models estimated the association between insurance type, CSCHN and EBDP status, and parent ratings of their child's insurance adequacy. Marginal effects were calculated for insurance type, CSHCN and EBDP status, and their interactions to estimate the size of the association. RESULTS: Among all subgroups, consistently more parents with publicly insured children rated their insurance as adequate compared to those with private insurance. Parents of privately insured CSHCN with EBDPs rated their insurance as adequate at significantly lower rates than any other group of parents (55%)-including those with privately insured children without EBDPs (non-CSHCN= 67%; CSHCN = 63%) and all other parents with publicly insured children (non-CSHCN = 87%; CSHCN = 83%; CSHCN with EBDPs = 84%). CONCLUSIONS: Future research should investigate if perceptions of insurance adequacy among families whose CSHCN has an EBDP aligns with reports of service access and unmet health care needs.

The Impact of COVID-19 on Pregnant Women and Children: Recommendations for Health Promotion.

COVID-19 continues to have severe repercussions on children and pregnant women. The repercussions include not only the direct impact of COVID-19 (ie, children getting infected by COVID-19) but also indirect impacts (eg, safeguarding from child maltreatment, obesogenic behaviors, language and socioemotional development, educational consequences [eg, interrupted learning]; social isolation; mental health; behavioral health [eg, increased substance use in adolescence]; health and economic impact of COVID-19 on caregivers and family relationships. It has also shed light on long-standing structural and socioeconomic issues, including equity in nutrition and food security, housing, childcare, and internet access. Using a socioecological, life course, and population health approach, we discuss the implications for pregnant women and children's health and well-being and give recommendations for mitigating the short and long-term deleterious impact COVID- 19 on women, children, and their families.

Identification of PADI2 as a potential breast cancer biomarker and therapeutic target.

BACKGROUND: We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects. METHODS: RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes. RESULTS: We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 × 106) in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu) mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of Cl-amidine treated and control MCF10DCIS cells, and found that the PADI inhibitor strongly affects the expression of several cell cycle genes implicated in tumor progression, including p21, GADD45α, and Ki67. CONCLUSION: Together, these results suggest that PADI2 may function as an important new biomarker for HER2/ERBB2+ tumors and that Cl-amidine represents a new candidate for breast cancer therapy.

Beyond "Disconnected Youth": Characterizing Developmental Heterogeneity in School or Work Connections During Emerging Adulthood.

Prior research on disconnected youth has defined connectedness to school or work during emerging adulthood as an either/or outcome, conflicting with research on emerging adulthood, which suggests varied, individualized pathways. This study used a growth mixture model method with data from the Panel Study of Income Dynamics Transition into Adulthood Supplement to elucidate developmental heterogeneity in connectedness to school or work during emerging adulthood (n = 1,977). Results indicated distinct subgroups of connectedness to school or work with additional variation within groups. Racialized group and parenting status differentiated between being fully connected or not but did not explain differences among those with less consistent connectedness. Policy implications include that the timing and duration of policies targeting disconnected youth may be missing a substantial minority of young people. Re-thinking supports for disconnected youth can be further informed by future research focused on examining factors related to individual differences in the timing and nature of connectedness to school or work.

The impacts of COVID-19 on LGBTQ+ foster youth alumni.

BACKGROUND: LGBTQ+ youth frequently experience disparities in outcomes related to permanency and overall well-being while in out-of-home care. These negative outcomes often persist after youth have transitioned out of care, particularly in the domains of housing, education, employment, and mental health. Initial research has found that the ongoing COVID-19 pandemic has exacerbated negative physical and mental health outcomes, as well as decreased economic stability among transition age youth. OBJECTIVE: This study seeks to determine if COVID-19 has resulted in unique impacts on foster care alumni, and if these impacts are the same for LGBTQ+ and non-LGBTQ+ transition age youth. PARTICIPANTS AND SETTING: This study used data from the 2020 Jim Casey Youth Opportunities Initiative Opportunity Passport Survey to explore these questions. METHODS: This survey was administered electronically to a national sample of 1223 youth ages 18-26 with lived experience in foster care. RESULTS: Results indicate that relative to non-LGBTQ+ foster care alumni, LGBTQ+ foster care alumni experienced more negative outcomes in housing stability, employment, and mental health/trauma due to COVID-19. No significant differences were found for education-related impacts. Outcomes varied by sex assigned at birth, ethnicity, and sexual orientation, gender identity and expression (SOGIE) of respondents, with female respondents, black, indigenous and other people of color (BIPOC) youth and LGBTQ+ youth being most frequently impacted. CONCLUSIONS: Results indicate that relative to non-LGBTQ+ foster care alumni, LGBTQ+ foster care alumni experienced more negative outcomes in housing stability, employment, and mental health/trauma due to COVID-19. No significant differences were found for education-related impacts. Outcomes varied by sex assigned at birth, ethnicity, and sexual orientation, gender identity and expression (SOGIE) of respondents, with female respondents, BIPOC youth and LGBTQ+ youth being most frequently impacted. Implications for practice and policy are explored.

Experiences of discrimination among young adults experiencing homelessness: Relationship to mental health outcomes.

Young adults experiencing homelessness (YAEH) are at high risk for discrimination. Limited research has documented the extent of discrimination experiences and their relationship to mental health outcomes among this group. This study used data from YAEH who completed self-administered surveys across seven U.S. cities (N = 1,426) to examine the rates and correlates of discrimination experiences and their association with psychological distress and suicidal ideation. Chi-square and multivariate logistic regressions were used to examine the relations between perceived discrimination and race, gender identity, sexual orientation, foster care history, criminal justice history, reasons for homelessness, and length of time homeless. Then, logistic regression was used to examine whether discrimination increased the odds of psychological distress and suicidal ideation, controlling for other factors. Three-fourths (75.8%) of the sample (n = 1,055) reported experiencing at least one of the five forms of everyday discrimination experiences at least a few times a year, with the most common reason attributed to their housing situation (46%). Sexual orientation, juvenile justice involvement, and having been homeless for 2 years or more were associated with increased odds of experiencing discrimination. Discrimination was a strong predictor of psychological distress but was significant only at the bivariate level for suicidal ideation. Study results suggest that experiences of discrimination are common among YAEH and that these experiences increase risk for psychological distress. Providers working with YAEH need to validate and acknowledge the impact of these experiences on mental health. And, communities need to work to reduce discrimination experiences by targeting stigma against YAEH. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1-/- mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. METHODS: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1-/- (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. FINDINGS: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1-/- mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. INTERPRETATION: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. FUNDING: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust.

Characteristics of Emergency Department Visits by Homeless Young Adults in the U.S.

PURPOSE: Homeless young adults often seek health care at emergency departments (EDs) after they are no longer able to ignore a pressing health problem. However, a dearth of literature examines homeless young adults' ED visits. This study aimed to increase understanding of ED visits among homeless young adults within the U.S. METHODS: Data for this study were obtained from the 2011-2015 National Hospital Ambulatory Medical Care Survey. The sample for this study included all ED visits made by homeless and housed young adults aged 18-29 years (unweighted N = 25,068). RESULTS: ED visits by homeless young adults were distinguished in terms of gender, region, payment sources, and triage level. Furthermore, ED visits made by homeless young adults were more likely related to mental health and suicide. Homeless young adults' ED visits were characterized by a longer average length of stay and were less likely to be referred to a physician or clinic for follow-up, given medication, or have a procedure performed in the ED. CONCLUSIONS: This study highlighted differences in ED utilization for homeless young adults. The findings of this study suggest a need to further examine the characteristics of ED services received by homeless young adults to better understand differences in ED service receipt related to housing status. This knowledge can inform efforts to reduce costs through improving access to housing and outpatient mental health care and reducing stigma among health care professionals to ensure continuity of care.

A Pilot Study of Peer-to-Peer SBIRT Simulation as a Clinical Telehealth Training Tool During COVID-19.

Screening, Brief Intervention and Referral to Treatment (SBIRT), is an evidence-based approach to screening and early intervention for those at risk of substance use disorders. With the ongoing health concerns related to COVID-19, there is an increased need for social workers who can competently deliver evidence-based interventions, such as SBIRT, via telehealth. Due to the COVID-19 pandemic, traditional SBIRT training approaches using face-to-face (FTF) instruction and FTF simulated practice may not be a safe or feasible way to develop students' SBIRT- related skills. This study explores 35 social work graduate students' experiences of learning SBIRT skills in a remote learning format and subsequently delivering a SBIRT intervention to a live "client" via a peer-to-peer simulated telehealth session. Overall, students reported that the shift from FTF to remote learning made learning SBIRT skills difficult, and that providing brief intervention and referral was the most difficult step of the simulated SBIRT telehealth intervention. Qualitative feedback indicates that overall, students found the simulated telehealth sessions a valuable learning experience, but also reported that richer educational experiences would have resulted from additional practice opportunities and real time feedback. Implications for future research, simulation-based education and clinical practice are discussed.

Screening for trauma and behavioral health needs in child welfare: Practice implications for promoting placement stability.

BACKGROUND: Although the child welfare field has initiated efforts to use standardized screening for trauma and behavioral health needs, research has rarely examined whether these screenings have influenced permanency outcomes. OBJECTIVE: Using data from three states' federal demonstration projects, we examined whether receipt of trauma and behavioral health screening and results of screening were associated with placement stability (i.e., fewer placements). Our inquiry focused on whether similar patterns of statistical associations would be observed in three distinct state settings. PARTICIPANTS AND SETTING: Samples comprised children in out-of-home care in three states newly implementing trauma and behavioral health screening. The states included a South Central state, New England state, and a Central Midwestern state. RESULTS: In all three states, findings showed children who received screening had a higher number of placements (i.e., placement instability). Likewise, all three states found that children whose screening results indicated greater need, such as higher number of trauma symptoms or lower behavioral health functioning, were more likely to experience a higher number of placements (i.e., placement instability). CONCLUSION: Despite differences in screening tools and state-specific approaches, findings suggest that early screenings may provide important information that could be used to identify children's needs, make appropriate service referrals, establish well-matched placements, and support resource parents and birth parents toward better permanency outcomes. Regardless of potential benefits of early screening, it may be underutilized in the field. Future research is needed to replicate these findings and continue to build an evidence base for trauma and behavioral health screening.

Does it all add up?

Flaws in Schedule H community benefit reporting will affect systems.

Investigating the Relationship between Trauma Symptoms and Placement Instability.

BACKGROUND: Placement stability while in foster care has important implications for children's permanency and well-being. Though a majority of youth have adequate placement stability while in foster care, a substantial minority experience multiple moves during their time in care. Research on correlates of placement instability has demonstrated a relationship between externalizing behaviors and placement instability. Likewise, evidence suggests higher levels of trauma are associated with increased externalizing behaviors. However, few studies have examined the relationship between trauma symptoms and placement instability. OBJECTIVE: The purpose of this study was to investigate whether children with clinically significant trauma symptoms had higher odds of placement instability. PARTICIPANTS AND SETTING: Administrative data collected as a part of a summative evaluation for a federally-funded trauma III grant project were used. The sample included 1,668 children ages 5 and older who entered foster care during a 30-month period in a Midwestern state and completed a self-reported trauma screen within 120 days of entering care. METHODS: Hierarchical logistic regression was conducted to examine the contributions of trauma symptoms scores to placement instability, above and beyond demographic characteristics and case characteristics. RESULTS: Results from the final analytic model, which controlled for demographic and case characteristics, showed that children with clinically significant trauma symptoms (i.e., scores ≥19) had 46% higher odds of experiencing placement instability (OR = 1.46, 95% CIs [1.16, 1.82], p = .001). Findings support the need to screen for and treat trauma symptomology among youth in foster care.

Barriers Faced by Physicians in Screening for Substance Use Disorders Among Adolescents.

OBJECTIVE: This study identifies key barriers faced by primary care providers (PCP) in implementation of screening, brief intervention, and referral to treatment (SBIRT) services for substance use disorders among adolescents. METHODS: The authors used mixed methods, including 12 key informant interviews and a survey with 75 PCPs, to identify key barriers to PCP implementation of SBIRT services. RESULTS: Time constraints, challenges related to parental involvement, a perceived lack of effectiveness of brief intervention services, and lack of training in providing brief intervention were barriers to screening and brief intervention. Referral to treatment was frequently perceived as a challenge. Increased reimbursement and dedicated resources were important interventions for improving screening rates. CONCLUSIONS: Increased reimbursement could support workflow enhancements to improve the consistency of SBIRT procedures and alleviate time constraints. Consistent SBIRT applications for all adolescents could also be supported by increasing PCP training in brief intervention.

3D imaging of tissue integration with porous biomaterials.

Porous biomaterials designed to support cellular infiltration and tissue formation play a critical role in implant fixation and engineered tissue repair. The purpose of this Leading Opinion Paper is to advocate the use of high resolution 3D imaging techniques as a tool to quantify extracellular matrix formation and vascular ingrowth within porous biomaterials and objectively compare different strategies for functional tissue regeneration. An initial over-reliance on qualitative evaluation methods may have contributed to the false perception that developing effective tissue engineering technologies would be relatively straightforward. Moreover, the lack of comparative studies with quantitative metrics in challenging pre-clinical models has made it difficult to determine which of the many available strategies to invest in or use clinically for companies and clinicians, respectively. This paper will specifically illustrate the use of microcomputed tomography (micro-CT) imaging with and without contrast agents to nondestructively quantify the formation of bone, cartilage, and vasculature within porous biomaterials.

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties.

Articular cartilage undergoes matrix degradation and loss of mechanical properties when stimulated with proinflammatory cytokines such as interleukin-1 (IL-1). Aggrecanases and matrix metalloproteinases (MMPs) are thought to be principal downstream effectors of cytokine-induced matrix catabolism, and aggrecanase- or MMP-selective inhibitors reduce or block matrix destruction in several model systems. The objective of this study was to use metalloproteinase inhibitors to perturb IL-1-induced matrix catabolism in bovine cartilage explants and examine their effects on changes in tissue compression and shear properties. Explanted tissue was stimulated with IL-1 for up to 24 days in the absence or presence of inhibitors that were aggrecanase-selective, MMP-selective, or non-selective. Analysis of conditioned media and explant digests revealed that aggrecanase-mediated aggrecanolysis was delayed to varying extents with all inhibitor treatments, but that aggrecan release persisted. Collagen degradation was abrogated by MMP- and non-selective inhibitors and reduced by the aggrecanase inhibitor. The inhibitors delayed but did not reduce loss of the equilibrium compression modulus, whereas the losses of dynamic compression and shear moduli were delayed and reduced. The data suggest that non-metalloproteinase mechanisms participate in IL-1-induced matrix degradation and loss of tissue material properties.