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OBJECTIVE: Type IX collagen is an important component of the intervertebral disc extracellular matrix. Mutations in type IX collagen are associated with premature disc degeneration in mice and a predisposition to disc disorders in humans. The aim of this study was to assess the prevalence and timeline of intervertebral disc degeneration in mice homozygous for an inactivated Col9a1 gene. METHODS: Intact spine segments were harvested from wild-type (WT) and type IX collagen-knockout (Col9a1(-/-)) mice at 3, 6, and 12 months of age. Sagittal spine sections were evaluated for evidence of histologic changes, by 2 blinded graders, using a semiquantitative grading method. RESULTS: There was evidence of more degeneration of the disc and end plate in the spines of Col9a1(-/-) mice compared with those of WT controls, at most time points. These findings were significant for the disc region at 3 and 6 months (P < 0.01) and at 12 months (P < 0.10) and for the end plate region only at 6 months (P < 0.10). Degenerative changes in the disc consisted of cellular changes and mucous degeneration. Degeneration in the end plates was associated with more cell proliferation, cartilage disorganization, and new bone formation. CONCLUSION: A deletion mutation for type IX collagen is associated with connective tissue changes characteristic of musculoskeletal degeneration in bony and cartilaginous tissue regions. Some of the observed changes were similar to cartilage changes in osteoarthritis, while others were more similar to disc degenerative changes in humans. The finding of premature onset of intervertebral disc degeneration in this mouse model may be useful in studies of the pathology and treatment of human disc degeneration. [ABSTRACT FROM AUTHOR]

Background: Perinatal mental health disorders affect up to 20% of all women. Women of refugee background are likely to be at increased risk, yet little research has explored this. This study aimed to assess if women of refugee background are more likely to screen risk positive for depression and anxiety than non-refugee women, using the Edinburgh Postnatal Depression Scale (EPDS); and if screening in pregnancy using the EPDS enables better detection of depression and anxiety symptoms in women of refugee background than routine care., Methods: This implementation study was conducted at an antenatal clinic in Melbourne, Australia. Women of refugee and non-refugee backgrounds were screened for depression using English or translated versions of the EPDS and a psychosocial assessment on a digital platform. The psychosocial assessment records of 34 women of refugee background receiving routine care (no screening) were audited., Results: Overall, 274 women completed the EPDS; 43% of refugee background. A similar proportion of women of refugee and non-refugee backgrounds had EPDS scores of ≥9 (39% vs. 40% p = 0.93). Women receiving the combined EPDS and psychosocial screening were more likely to receive a referral for further support than women receiving routine care (41% vs. 18%, p = 0.012)., Conclusion: Similarly, high proportions of women of refugee and non-refugee backgrounds were at increased risk of experiencing a current depressive disorder in early pregnancy, suggesting pregnancy care systems should acknowledge and respond to the mental health needs of these women. Screening appeared to facilitate the identification and referral of women compared to routine care., (© 2023 The Authors. Birth published by Wiley Periodicals LLC.)

Pregnancy carries substantial risk for developing lower urinary tract symptoms (LUTSs), with potential lifelong impacts on bladder health. Little is known about modifiable psychosocial factors that may influence the risk of postpartum LUTSs. We examined associations between depressive symptoms, perceived stress, and postpartum LUTSs, and the moderating effects of perceived social support, using data from a cohort study of Expect With Me group prenatal care (n = 462). One year postpartum, 40.3% participants reported one or more LUTS. The most frequent LUTS was daytime frequency (22.3%), followed by urinary incontinence (19.5%), urgency (18.0%), nocturia (15.6%), and bladder pain (6.9%). Higher odds of any LUTS were associated with greater depressive symptoms (adjusted odds ratio (AOR) 1.08, 95% confidence interval (CI) 1.04-1.11) and perceived stress (AOR 1.12, 95% CI 1.04-1.19). Higher perceived social support was associated with lower odds of any LUTS (AOR 0.94, 95% CI 0.88-0.99). Perceived social support mitigated the adverse effects of depressive symptoms (interaction AOR 0.99, 95% CI 0.98-0.99) and perceived stress (interaction AOR 0.97, 95% CI 0.95-0.99) on experiencing any LUTS. Greater depressive symptoms and perceived stress may increase the likelihood of experiencing LUTSs after childbirth. Efforts to promote bladder health among postpartum patients should consider psychological factors and social support.

Background Despite guideline-recommended use of oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF), OAC medication adherence among patients with AF in the United States ranges from 47% to 82%. To characterize potential causes of nonadherence, we analyzed associations between community and individual social risk factors and OAC adherence for stroke prevention in AF. Methods and Results A retrospective cohort analysis of patients with AF was conducted using the IQVIA PharMetrics Plus claims data from January 2016 to June 2020, and 3-digit ZIP code-level social risk scores were calculated using American Community Survey and commercial data. Logistic regression models evaluated associations between community social determinants of health, community social risk scores for 5 domains (economic climate, food landscape, housing environment, transportation network, and health literacy), patient characteristics and comorbidities, and 2 adherence outcomes: persistence on OAC for 180 days and proportion of days covered ≥0.80 at 360 days. Of 28 779 patients with AF included in the study, 70.8% of patients were male, 94.6% were commercially insured, and the average patient age was 59.2 years. Multivariable regression found that greater health literacy risk was negatively associated with 180-day persistence (odds ratio [OR]=0.80 [95% CI, 0.76-0.83]) and 360-day proportion of days covered (OR, 0.81 [95% CI, 0.76-0.87]). Patient age and higher AF stroke risk score and AF bleeding risk scores were positively associated with both 180-day persistence and 360-day proportion of days covered. Conclusions Social risk domains, such as health literacy, may affect OAC adherence among patients with AF. Future studies should explore associations between social risk factors and nonadherence with greater geographic granularity.

Objectives: Community health worker (CHW) programs are a promising strategy to improve maternal and child health outcomes, particularly among low-resource women. Yet, little is known about which aspects of CHW-client relationships are most salient for promoting positive change. This paper examines features of the CHW-client relationship that perinatal women with chronic conditions reported as being beneficial for their experience of prenatal care and pregnancy., Methods: Focus groups and interviews were conducted with 18 CHWs and 39 clients from three Merck for Mothers-funded programs in the Eastern United States. Data were analyzed using a grounded theory-informed thematic approach., Results: CHWs built trust-based relationships through emotional attendance, authenticity, and prioritization of clients' needs. They provided instrumental, informational, and emotional support that clients reported facilitated greater engagement with the healthcare system, improved health behaviors, and reduced stress. CHWs and clients alike viewed their relationships as having long-lasting impacts, made possible by the trust-based bond between them., Discussion: Strong, trusting relationships with CHWs may be one avenue through which to improve maternal and infant health for vulnerable perinatal women. Community health care programs should promote trust-building as an explicit program goal. Trust-based CHW-client relationships may serve as an exemplar for transforming traditional care relationships between providers and clients, leading to greater client engagement in care and improved health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pronounced racial disparities in maternal and infant health outcomes persist in the United States. Using an ecosocial and intersectionality framework and biopsychosocial model of health, we aimed to understand Black pregnant women's experiences of gendered racism during pregnancy., Methods: We conducted semistructured interviews with 24 Black pregnant women in New Haven, Connecticut. We asked women about their experience of being pregnant, experiences of gendered racism, and concerns related to pregnancy and parenting Black children. Transcripts were coded by three trained analysts using grounded theory techniques., Results: Women experienced gendered racism during pregnancy-racialized pregnancy stigma-in the form of stereotypes stigmatizing Black motherhood that devalued Black pregnancies. Women reported encountering assumptions that they had low incomes, were single, and had multiple children, regardless of socioeconomic status, marital status, or parity. Women encountered racialized pregnancy stigma in everyday, health care, social services, and housing-related contexts, making it difficult to complete tasks without scrutiny. For many, racialized pregnancy stigma was a source of stress. To counteract these stereotypes, women used a variety of coping responses, including positive self-definition., Conclusions: Racialized pregnancy stigma may contribute to poorer maternal and infant outcomes by way of reduced access to quality health care; impediments to services, resources, and social support; and poorer psychological health. Interventions to address racialized pregnancy stigma and its adverse consequences include anti-bias training for health care and social service providers; screening for racialized pregnancy stigma and providing evidence-based coping strategies; creating pregnancy support groups; and developing a broader societal discourse that values Black women and their pregnancies., (Copyright © 2020 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Problem: National guidelines recommending mental health screening in pregnancy have not been implemented well in routine maternity care. Women of refugee background are likely to have experienced traumatic events and resettlement stressors, yet are not often identified with mental health issues in the perinatal period., Background: Globally, perinatal mental health conditions affect up to 20% of women. Many difficulties in accessing mental health care in pregnancy exist for women of refugee background including stigma, and cultural and language barriers. Technology can provide an efficient and effective method to overcome some of these barriers., Aim: To determine if a digital perinatal mental health screening program is feasible and acceptable for women of refugee background., Methods: This qualitative evaluation study used focus group and semi-structured telephone interviews with refugee and migrant women from four communities. Interpreters were used with women who spoke little or no English. Data were analysed using both an inductive and deductive approach to thematic analysis., Findings: Under the three key themes: 'Women's experiences of perinatal mental health screening in pregnancy'; 'Barriers and enablers to accessing ongoing mental health care' and 'Improvements to the program: the development of audio versions', women found the program feasible and acceptable., Discussion: Screening using a mobile device offered women more privacy and opened up discussions with midwives on emotional health. Improvements in service coordination and access to further mental health management for women is required., Conclusion: Perinatal mental health screening is an acceptable and feasible option for women of refugee background. Integrated models of care, case management, and patient navigators are options for improvements in uptake of referral and treatment services., (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Problem: National guidelines recommend repeated screening for depression and anxiety for all women in the perinatal period. Routine screening in pregnancy is limited due to service, community and individual barriers., Background: Perinatal depression and perinatal anxiety affect up to 20% of all women. Women of refugee background are at even greater risk for perinatal mental health conditions due to refugee experiences and resettlement stressors., Aim: To evaluate the acceptability and feasibility of a perinatal mental health screening program for women of refugee background from the perspective of health professionals., Methods: A mixed methods design guided by the Normalization Process Theory was used. Data were collected at a dedicated refugee antenatal clinic in the south-eastern suburbs of Melbourne, Australia. An online survey (n=38), focus groups (n=2; 13 participants) and semi-structured interviews (n=8; 11 participants) with health professionals were conducted., Findings: Under the four constructs of the Normalization Process Theory, health professionals reported improvements in identifying and referring women with mental health issues, more open and in-depth conversations with women about mental health and valued using an evidenced-based measure. Key issues included professional development, language barriers and time constraints., Discussion: Implementing a perinatal mental health screening program has been positively received. Strategies for sustainability include professional development and the addition of audio versions of the measures., Conclusion: This perinatal mental health screening program is acceptable and a feasible option for health professionals. Health professionals value providing more holistic care and have more open discussion with women about mental health., (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objectives: Community health workers (CHWs) are a critical part of the healthcare workforce and valuable members of healthcare teams. However, little is known about successful strategies for sustaining CHW programs. The aim of this study is to identify institutional and community factors that may contribute to the sustainability of CHW programs to improve maternal health outcomes., Methods: We conducted focus groups and in-depth interviews with 54 CHWs, CHW program staff, and community partners involved in implementing three Merck for Mothers-funded CHW programs in the United States serving reproductive-age women with chronic health conditions. Additionally, a review of documents submitted by CHW programs during the evaluation process provided context for our findings. Data were analyzed using an inductive qualitative approach., Results: Three themes emerged in our analysis of factors that may influence the sustainability of CHW programs to improve maternal health: CHW support from supervisors, providers, and peers; relationships with healthcare systems and insurers; and securing adequate, continuous funding. Key findings include the need for CHWs to have strong supervisory structures, participate in regular care team meetings, and interact with peers; advantages of CHWs having access to electronic health records; and importance of full-cost accounting and developing a broad base of financial support for CHW programs., Conclusion: Research should continue to identify best practices for implementation of such programs, particularly regarding effective supervisory support structures, integration of programs with healthcare systems, and long-term revenue streams.

Background: Group prenatal care is a promising strategy to improve perinatal outcomes. Research in larger more diverse populations with attention to adherence is needed to inform clinical practice recommendations. We examined the impact of group prenatal care on preterm birth and low birth weight in a large metropolitan hospital, accounting for patient adherence, over an 8.5-year period., Materials and Methods: We analyzed data from 9,348 pregnant women with a live, singleton birth who received group (CenteringPregnancy or Expect With Me) or individual prenatal care at Vanderbilt University Medical Center from January 2009 through June 2016. Propensity scores were used for matching based on year of delivery, age, race, pregnancy risk, and adequacy of care. The propensity score matched sample included 1,384 group and 5,055 individual prenatal care patients (total = 6,439 women). Preterm birth (<37 weeks gestation) and low birth weight (<2,500 g) were obtained from systematic medical review. Risks were estimated using Poisson regression., Results: Controlling for individual visits, receiving group prenatal care resulted in significantly lower risk of having a preterm birth (Rate ratio [RR] 0.63, 95% confidence interval [CI] 0.49-0.81) and low birth weight baby (RR 0.62, 95% CI 0.47-0.81), compared to receiving individual care only. Women with ≥5 group prenatal care visits experienced even greater benefits: 68% (RR = 0.32; 95% CI 0.22-0.45) and 66% (RR = 0.34; 95% CI 0.23-0.50) risk reduction in preterm birth and low birth weight, respectively., Conclusions: Participation in group prenatal care may improve birth outcomes. Efforts to promote adoption and sustainability of group prenatal care by health systems may be warranted.

Adolescents in stepfamilies and single-parent families tend to report lower levels of well-being than adolescents who live with two biological parents. Using data from Add Health ( n = 16,684), the present study builds upon this literature by examining family-level predictors of adolescent depressive symptoms, delinquency, failing a class, heavy alcohol use, tobacco use, and marijuana use. We focus on feelings of family belonging as a predictor of adolescent well-being and find that this measure is significantly associated with well-being in all family types, and particularly in two-biological-parent families. In addition, results indicate that family belonging mediates associations between parent-adolescent closeness and well-being for most outcomes.

Objectives Culture and religion are important in advance care planning (ACP), yet it is not well understood how this is represented in ACP online resources. The aim of the present study was to identify the availability of Australian-based ACP websites and online informational booklets containing cultural and religious information. Methods An environmental scanning framework was used with a Google search conducted from 30 June 2015 to 5 July 2015. Eligible Australian-based ACP websites and online informational booklets were reviewed by two analysts (APS & PM) for information pertaining to at least one culture or religion. Common characteristics were agreed upon and tabulated with narrative description. Results Seven Australian-based ACP websites were identified with varying degrees of cultural and religious information. Seven Australian-based ACP informational booklets were identified addressing culture or religion, namely of Aboriginal and Torres Strait Islander (n=5), Sikh (n=1) and Italian (n=1) communities. Twenty-one other online resources with cultural and religious information were identified, developed within the context of health and palliative care. Conclusions There is no comprehensive Australian-based ACP website or informational booklet supporting ACP across several cultural and religious contexts. Considering Australia's multicultural and multifaith population, such a resource may be beneficial in increasing awareness and uptake of ACP. What is known about the topic? Health professionals and consumers frequently use the Internet to find information. Non-regulation has resulted in the proliferation of ACP online resources (i.e. ACP websites and online informational booklets). Although this has contributed to raising awareness of ACP, the availability of Australian-based ACP online resources with cultural and religious information is not well known. What does this paper add? This paper is the first to use an environmental scanning methodology to identify Australian-based ACP websites and online informational booklets with cultural and religious information. What are the implications for practitioners? The results of this environmental scan present the availability of Australian-based ACP websites and online informational booklets containing cultural and religious information. A thorough understanding may assist in identifying gaps for future ACP project planning and policy objectives, consistent with meeting cultural and religious needs. This may be beneficial for health professionals, consumers, health associations, organisations and government policy makers concerned with ACP.

Rationale: Persistent racial disparities in adverse birth outcomes are not fully explained by individual-level risk factors. Racial residential segregation-degree to which two or more groups live apart from one another-may contribute to the etiology of these birth outcome disparities. Our aim was to assess associations between segregation and adverse birth outcomes by race. This review focused on formal measures of segregation, using Massey and Denton's framework (1998) that identifies five distinct operationalizations of segregation, in addition to proxy measures of segregation such as racial composition, in order to gain a deeper understanding of the operationalizations of segregation most salient for birth outcomes., Method: Review and meta-analyses were conducted using PubMed, PsycINFO and Web of Science and included articles from inception through April 30, 2017., Results: Forty-two articles examined associations between segregation and adverse birth outcomes among Black and White mothers separately. Meta-analyses showed that among Black mothers, exposure was associated with increased risk of preterm birth (OR = 1.17, 95% CI = 1.10, 1.26), and low birth weight (OR = 1.13, 95% CI=1.06, 1.21), and Black racial composition was associated with increased risk of preterm birth (OR = 1.20, 95% CI=1.05, 1.37), among those living in most- compared to least-segregated neighborhoods. Few studies were conducted among White mothers and only exposure was associated with increased risk of preterm birth and low birth weight. Qualitative analyses indicated that among Black mothers, exposure and hypersegregation were associated with multiple adverse birth outcomes; findings were mixed for evenness and clustering., Conclusions and Future Directions: Associations between segregation and adverse birth outcomes differ by race. Methodological heterogeneity between studies may obscure true associations. Research can be advanced through use of multilevel frameworks and by examining mechanistic pathways between segregation and adverse birth outcomes. Elucidation of pathways may provide opportunities to intervene to reduce seemingly intractable racial disparities in adverse birth outcomes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adolescents' perceptions of family belonging are associated with several well-being indicators, yet we know little about which factors influence these perceptions or how they differ by family structure. The current study uses nationally representative data from Add Health to examine predictors of adolescents' perceptions of family belonging in two-biological-parent families ( n = 9686). The results are compared to a recent study using Add Health that examined family belonging in married mother-stepfather families. Findings suggest both similarities and differences across family structure in the factors associated with family belonging.

We used FDA-approved, edible materials to fabricate superhydrophobic coatings in a simple, low cost, scalable, single step process. Our coatings display high contact angles and low roll off angles for a variety of liquid products consumed daily and facilitate easy removal of liquids from food containers with virtually no residue. Even at high concentrations, our coatings are nontoxic, as shown using toxicity tests.

Prior research has established that adolescents' perceptions of family belonging are associated with a range of well-being indicators and that adolescents in stepfamilies report lower levels of family belonging than adolescents in two-biological-parent families. Yet, we know little regarding what factors are associated with adolescents' perceptions of family belonging in stepfamilies. Guided by family systems theory, the authors addressed this issue by using nationally representative data (Add Health) to examine the associations between family characteristics and adolescents' perceptions of family belonging in stepfather families ( N = 2,085). Results from structural equation models revealed that both the perceived quality of the stepfather-adolescent relationship, and in particular the perceived quality of the mother-adolescent relationship, were the factors most strongly associated with feelings of family belonging.

Objective: In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be associated with these pathologies., Methods: Col9a1(-/-) and wild-type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration., Results: Col9a1(-/-) mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1(-/-) mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1(-/-) mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1(-/-) mice having an increased incidence of disc tears., Conclusion: These data describe a Col9a1(-/-) behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1(-/-) mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1(-/-) mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.

Background: Duration of survival of cats with naturally occurring chronic kidney disease (CKD) is poorly characterized., Hypothesis: Stage of kidney disease based on serum creatinine concentration (SCr) at the time of diagnosis and after correction of prerenal azotemia is strongly associated with duration of survival in cats., Animals: Two hundred and eleven client-owned cats with naturally occurring CKD evaluated between April 2000 and January 2002., Methods: Retrospective case review of 733 cats with SCr > 2.3 mg/dL. Examination of the medical records identified 211 cats that met all other inclusion and exclusion criteria for this study. Clinical characteristics, clinicopathologic data, and survival times were extracted from the medical record. Owners and referring veterinarians were contacted by phone to obtain follow-up if it was not documented in the record. Kaplan-Meier survival curves were performed to determine survival times for International Renal Interest Society (IRIS) stage both at diagnosis and at baseline (ie, after correction of prerenal azotemia)., Results: Median survival for cats in IRIS stage IIb at the time of diagnosis was 1,151 days (range 2-3,107), and was longer than survival in stage III (median 778, range 22-2,100) or stage IV (median 103, range 1-1,920) (P-value< .0001). P-value for effect of stage at diagnosis was < .0001., Conclusions and Clinical Importance: IRIS stage of CKD based on serum creatinine at the time of diagnosis is strongly predictive of survival in cats with naturally occurring CKD.

Listeria innocua M1 has been used by many researchers as a nonpathogenic thermal processing surrogate for Listeria monocytogenes. However, L. innocua M1 has been criticized because its thermal survivability characteristics are not as closely parallel to L. monocytogenes as some would like in a variety of foods and processing conditions. The present study was conducted to compare multiple L. innocua and L. monocytogenes strains to validate L. innocua M1 as the ideal surrogate under high-temperature thermal processing conditions for L. monocytogenes. The D- and z-values of L. innocua M1, L. innocua strain SLCC 5639 serotype (6a), SLCC 5640 (6b), SLCC 2745 (4ab), and L. monocytogenes F4243 (4b) were calculated for raw hamburger patties. Hamburger patties were inoculated with 10(7-8) CFU/g of L. monocytogenes or L. innocua. Samples were heat treated at 4 temperatures (62.5 to 70 degrees C). At each temperature, the decimal reduction time (D-value) was obtained by linear regression of survival curves. The D- and z-values were determined for each bacterium. The D-values of L. innocua and L. monocytogenes serotypes ranged from 3.17 to 0.13 min at 62.5 to 70 degrees C, and the z-values of L. innocua and L. monocytogenes were 7.44 to 7.73 degrees C. Two of the 4 L. innocua serotypes used in this experiment have the potential for use as surrogates in hamburger meat with varying margins of safety. L. innocua M1 should serve as the primary nonpathogenic surrogate with the greatest margin of safety in verifying a new thermal process to destroy L. monocytogenes.

The objectives of augmentation of the nucleus pulposus following disc removal are to prevent disc height loss and the associated biomechanical and biochemical changes. Flowable materials may be injected via a small incision, allowing minimally invasive access to the disc space. Fluids can interdigitate with the irregular surgical defects and may even physically bond to the adjacent tissue. Injectable biomaterials allow for incorporation and uniform dispersion of cells and/or therapeutic agents. Injectable biomaterials have been developed that may act as a substitute for the disc nucleus pulposus. Our work has focused on the evaluation of a recombinant protein copolymer consisting of amino acid sequence blocks derived from silk and elastin structural proteins as an injectable biomaterial for augmentation of the nucleus pulposus. This implant, NuCoretrade mark Injectable Nucleus is being developed by Spine Wave (Shelton, CT). The NuCoretrade mark material is comprised of a solution of the protein polymer and a polyfunctional cross-linking agent. The material closely mimics the protein content, water content, pH and complex modulus of the natural nucleus pulposus. Extensive mechanical testing, biocompatibility and toxicology testing have been performed on the material. Characterization studies indicate that the NuCoretrade mark Injectable Nucleus is able to restore the biomechanics of the disc following a microdiscectomy. Extensive biomaterial characterization shows the material to be non-toxic and biocompatible. The mechanical properties of the material mimic those of the natural nucleus pulposus. Thus NuCoretrade mark Injectable Nucleus is suitable to replace the natural nucleus pulposus following a discectomy procedure. Human clinical evaluation is underway in a multi center clinical study on the use of the material as an adjunct to microdiscectomy. Further clinical studies of the use of NuCoretrade mark Injectable Nucleus for treatment of early stage degenerative disc disease are planned in the near future. On-going efforts are characterizing the use of the material as a cell delivery vehicle for disc repair and reconstruction. Related development efforts are exploring methods for repair and regeneration of the cartilage endplate that are implemented to enhance the host-implant interface. Prior to the introduction of the above-mentioned biomaterial, our work proposes to utilize a process for the treatment of the vertebral endplates. The goal of this process is to restore the endplates as closely as possible to their natural state prior to disease or degeneration. The nature of the treatment will depend upon the form of the endplate degeneration and on the type of scaffolding that is intended to be introduced in the nuclear cavity. Endplate therapy is a potential means of enhancing biomaterial integration and cell survival, but remains a long-term and currently untested methodology.

Intervertebral disc (IVD) cells experience a broad range of physicochemical stimuli under physiologic conditions, including alterations in their osmotic environment. Cellular responses to altered osmolarity have been documented at the transcriptional and post-translational level, but mainly for extracellular matrix proteins. In this study, the gene expression profile of human IVD cells was quantified with gene array technology following exposure to increased osmolarity in order to capture the biological responses for a broad set of targets. A total of 42 genes were identified in IVD cells as significantly changed following culture under hyper-osmotic conditions. Gene expression patterns were verified using RT-PCR. Genes identified in this study include those related to cytoskeleton remodeling and stabilization (ephrin-B2, muskelin), as well as membrane transport (ion transporter SLC21A12, osmolyte transporter SLC5A3, monocarboxylic acid SLC16A6). An unexpected finding was the differential regulation of the gene for the neurotrophin, brain-derived neurotrophic factor, by hyper-osmotic stimuli that suggests a capability of IVD cells to respond to physicochemical stimuli with factors that may regulate discogenic pain.

Study Design: Matrix protein gene expression was determined for cells of the anulus fibrosus (AF) and nucleus pulposus (NP) regions of the intervertebral disc when cultured in AF or NP cell-conditioned medium., Objectives: To investigate changes in mRNA levels for type I collagen, type II collagen and aggrecan in cells of the AF and NP in response to cell-conditioned medium., Summary of Background Data: Cells of the intervertebral disc have been shown to respond to exogenous soluble mediators such as the growth factors TGF-beta and IGF-1. Little is known of their biologic response to endogenous factors that may be secreted locally or by cells of neighboring regions., Methods: Porcine cells were cultured for 48 hours in alginate gel in the presence or absence of conditioned medium. Gene expression for aggrecan and collagens was quantified using real-time reverse transcriptase-polymerase chain reaction. RESULTS.: AF cell gene expression was generally stimulated by the conditioned medium of either AF or NP cells. In contrast, the notochordal cell-containing NP cells showed little change in gene expression with either source of conditioned medium., Conclusions: Cells of the NP and AF secrete soluble factors in culture at similarly effective doses to stimulate matrix protein gene expression in AF cells of the intervertebral disc. Unlike AF cells, however, NP cell gene expression was not stimulated by any conditioned medium, suggesting that differences exist in the responsiveness of cells of notochordal (NP) and fibrocartilaginous (AF) phenotypes. Understanding these differences between cells of the intervertebral disc may reveal unique stimulatory factors important to repair and regeneration of the degenerated intervertebral disc.

The polybutester (PBE) suture has been coated with an absorbable polytribolate polymer that is composed of glycolide (9%), epsilon-caprolactone (51%), and poloxamer 188 (40%) to reduce its drag forces. It is the purpose of this study to document the influence of this coating on the biomechanical performance of both PBE sutures and polypropylene (PP) sutures. The performance parameters evaluated were breaking strength, elongation, stiffness, knot security, knot run down, and tissue drag. The breaking strength of PP sutures was remarkably similar to that of coated and uncoated PBE sutures. In size 5/0 PP sutures, the sutures exhibited considerably greater elongation at knot break than did comparably sized PBE sutures. The PBE suture elongated under low loads, but returned to its original length when the load was removed. In contrast, the PP suture elongated irreversibly at high loads, exhibiting creep. Coated and uncoated PBE sutures exhibited less stiffness than PP sutures and exhibited limited memory after removal from the suture package. Coating the PBE suture markedly reduced its drag forces in musculoaponeurotic, colonic, and vascular tissue. Knot security with the coated PBE suture was achieved with only one more throw than with comparably sized uncoated PBE sutures. On the basis of the results of this study, coating the PBE suture represents another major advance in suture performance.

Study Design: A variety of interbody implants were imaged by computed tomography and plain radiography within cadaveric spines to evaluate their basic imaging characteristics., Objectives: Sources of interpretation error by both computed tomography and plain radiography of interbody implants were investigated., Summary of Background Data: Lucencies have been reported around bone dowel implants in the postoperative period, which have been shown to resolve. The diagnosis of fusion through metallic implants has been difficult with both false-positive and false-negative results. The literature of imaging these implants is very sparse., Methods: Four interbody constructs were placed in cadaveric spines under different conditions and imaged using both computed tomography and plain film radiography., Results: Plain radiographs could not predict the presence of intraimplant bone whereas computed tomography was accurate. Metallic implants had a 1-3-mm computed tomography artifact limiting peri-implant interpretation. Lucencies could be seen on computed tomography but not on plain radiographs. However, the opposite was also seen. Lucencies around nonmetallic implants were more visible by a 4:1 ratio., Conclusions: Potential errors in interpretation were identified including assessment for bridging bone, assessment for lucency, and obscuration of peri-implant detail from metallic artifact. Lucencies were more visible with nonmetallic implants than with metallic constructs. Plain radiograph analysis of metallic implants tended to underestimate lucencies, whereas analysis of nonmetallic implants tended to overestimate lucencies.

Prior studies have demonstrated the presence of inhomogeneities in myocardial [K+]e after serial 10-minute occlusions of the left anterior descending coronary artery in the pig, even within restricted locations of an ischemic zone. These inhomogeneities are thought to underlie the electrophysiological abnormalities responsible for lethal ventricular arrhythmias through reentrant and nonreentrant pathways, but a clear association has not been demonstrated. As a prerequisite to establishing this association, these studies were performed to establish measurement standards for [K+]e inhomogeneity, to quantify the magnitude and time course of these inhomogeneities, to determine whether the inhomogeneities are greater in the ischemic border where lethal ventricular arrhythmias are known to originate, and to assess the effect of a known antifibrillatory drug on [K+]e inhomogeneities. [K+]e (expressed as the change in potassium equilibrium potential, dEK [mV]) was measured in 15 preparations using an average of 17 closely spaced, critically calibrated K(+)-sensitive electrodes having stable response characteristics. A series of four 10-minute occlusions each separated by a 50-minute reperfusion period were performed in each study. In half of the studies, intravenous verapamil (0.2 mg/kg bolus followed by 0.0065 mg/kg/hr) was administered before the fourth occlusion. In nine studies (five control and four verapamil), electrodes were placed in the marginal ischemic zone (from 2 mm outside to 5 mm inside the visible cyanotic border). In six other studies (three control and three verapamil), electrodes were placed in the central ischemic zone (10-20 mm within the ischemic region). We determined that the standard deviation is the best measure of inhomogeneity and that 12 equivalent measurement sites are required to estimate it with a satisfactory degree of statistical confidence. We found that after 10 minutes of ischemia, mean dEK was 1.6 times greater in the central than in the marginal ischemic zone, whereas mean standard deviation at the same time was 1.5 times greater in the marginal than in the central ischemic zone. Verapamil reduced mean dEK and mean standard deviation in both ischemic zones for most of the occlusion by delaying the rise in [K+]e and the inhomogeneity of that rise by 3-5 minutes. Comparisons of mean dEK with mean standard deviation revealed a steep linear relation in the marginal zone and a curvilinear relation in the central zone where higher mean dEK values were not accompanied by higher values for mean standard deviation. Furthermore, we determined that these relations were not altered by verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)

According to the literature one of the primary failure models of percutaneous devices (PDs) in soft tissue implantation sites is that of mechanically induced trauma along the implant/tissue interface. In order to avoid such avulsion, subcutaneous flanges have been incorporated into PD designs to provide a better distribution of stresses along the implant/tissue interface. Tissue necrosis and inflammation were then observed to be most pronounced around the rim of the subcutaneous flange. It was the goal of this study to develop and test PDs with subcutaneous flanges of varying stiffnesses in order to allow the flange to distribute stresses into the surrounding tissues more evenly, thereby reducing the likelihood of failure due to avulsion. PDs were tested with flanges of constant thickness or varying linearly, reducing toward the flange rim. They were evaluated using an in-vitro testing method which was designed to simulate the situation of an implanted PD subjected to external loading. The results indicated that the stiffness characteristics of the subcutaneous flange had a substantial effect on the behavior of the devices under loading. A PD having a radial stiffness decrease would improve the likelihood of implant survival in the clinical situation due to the reduction of mechanically induced trauma along the implant/tissue interface.

Studies were conducted to determine the effects of adenosine on transmural myocardial blood flow distribution. Both maximal and submaximal vasodilatory doses of adenosine were infused into awake resting dogs chronically instrumented with coronary flow probes and aortic and left atrial pressure catheters. Radioactive microspheres (8-10 micron) were used to determine regional coronary blood flow. Four experimental protocols were evaluated: 1) the effects of maximal (1.00 mg . kg-1 . min-1) as well as submaximal (0.45 mg . kg-1 . min-1) vasodilatory levels of adenosine, 2) the dose-response characteristics of adenosine, 3) the dose-response characteristics of dipyridamole, and 4) the effects of adenosine in the presence of an increased arterial PO2. The data indicate that maximal vasodilatory doses of adenosine have little effect on the endocardial-to-epicardial blood flow ratio, whereas submaximal doses result in a marked preferential endocardial perfusion. This relative increase in endocardial perfusion was not altered by hyperoxia. Dipyridamole, in submaximal doses, produced a similar preferential flow to the endocardial layer. These data demonstrate that the vasodilator reactivity to adenosine infusion is greater in the endocardial layer,

Leukotrienes are naturally occurring vasoactive metabolites of arachidonic acid that increase during inflammatory reactions and anaphylaxis. Coronary constriction and reduced myocardial contractility after leukotriene C4 and D4 administration were demonstrated in the isolated guinea pig heart. To explore the effects of leukotrienes in the in situ, blood-perfused heart, we administered leukotrienes C4, D4, and E4 into the coronary artery of the domestic pig. Increasing doses (0.1, 0.3, 1.0, and 3.0 micrograms) of leukotrienes C4, D4, and E4 were injected into the left anterior descending coronary artery of 8 open-chest domestic pigs. Significant dose-related reduction in coronary blood flow was observed after each leukotriene administration. Three micrograms of each leukotriene produced the following maximal decreases (mean +/- standard error); C4 = 80 +/- 9%, p less than 0.001; D4 = 81 +/- 3%, p less than 0.001; E4 = 64 +/- 12%, p less than 0.005. In several instances, surface electrograms recorded from the myocardial region exposed to leukotrienes showed signs of focal myocardial ischemia, sometimes accompanied by ventricular arrhythmia. Significant elevation of left ventricular end-diastolic pressure was observed after large doses (1 or 3 micrograms) of leukotrienes C4 and D4. Minimal (5 to 10%) decreases in mean arterial pressure and no change in heart rate were observed after leukotriene injection. We conclude that leukotrienes C4, D4, and E4 are extremely potent coronary constrictors in the in situ heart. The intensity of response and associated electrocardiographic signs of ischemia suggest that constriction is mainly due to a primary effect on vascular smooth muscle. However, coronary flow reduction may also reflect consequences of a primary negative inotropic action. Leukotrienes may play a significant role in the pathogenesis of a variety of cardiac disorders, particularly those associated with extensive inflammatory changes.

Intracoronary leukotriene D4, 0.1-3.0 micrograms (0.2-6.0 nmol), produced dose-dependent decreases in coronary flow of anesthetized pigs. Pretreatment with intracoronary FPL-55712 (0.1, 0.3 and 1.0 mg) reduced coronary constriction due to 1.0 micrograms leukotriene D4 by up to 77%. FPL-55712 did not produce sustained alterations in coronary flow, left ventricular end-diastolic pressure, systemic arterial pressure, or heart rate. Indomethacin pretreatment (6 mg/kg i.v.) had no effect on leukotriene-induced coronary constriction. Inhibition produced by FPL-55712 may be useful in disease states involving leukotriene-mediated coronary constriction.

The platelet-activating factor released by white blood cells and platelets has been shown to be 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). To fully understand the cardiovascular actions of this substance, we examined the effects of AGEPC on coronary blood flow (CBF) and other hemodynamic parameters in anesthetized open-chest domestic pigs. Mean arterial blood pressure (MBP), electrocardiogram, heart rate (HR), left ventricular pressure, and CBF were continuously recorded. AGEPC was injected (bolus, 0.1 ml) into the left anterior descending coronary artery at increasing doses of 0.03-10 nmol. Intracoronary AGEPC produced biphasic changes in CBF: a dose-dependent increase in CBF (up to 50%) followed by a decrease (up to 92%) in CBF. The changes in CBF were not directly related to any systemic effect, although MBP was reduced consistently after a dose higher than 1 nmol of AGEPC. The increase in CBF produced by AGEPC was not affected by pretreatment with indomethacin (6 mg/kg) or FPL 55712 (1 or 3 mg), an inhibitor of slow-reacting substance of anaphylaxis (SRS-A). The decrease in CBF produced by AGEPC was attenuated by FPL 55712 and blocked by indomethacin. These data suggest that AGEPC release from aggregating platelets might play a major role in modulating CBF and cardiac function in states involving platelet-coronary interaction.

Recent studies show that leukotrienes (LTs) produce profound coronary artery constriction. Although calcium entry blockers are commonly used to remedy coronary vasospasm, their capacity to interfere with LT-mediated coronary constriction is unknown. Therefore, we compared effects of intracoronary LTD4 before and during treatment with calcium entry blockers in the in situ, blood-perfused hearts of domestic pigs. Intravenous administration of verapamil (0.1-1.6 mg/kg), nifedipine (10 or 100 micrograms/kg) or diltiazem (0.6-2.0 mg/kg) sufficient to increase base-line coronary blood flow (CBF) and decrease mean arterial pressure did not change decrement in CBF after LTD4. Infusion of verapamil (0.01-0.04 mg/min) into the left anterior descending coronary artery raised pre-LTD4 CBF almost 2-fold without alteration in mean arterial pressure, heart rate or left ventricular end-diastolic pressure. Intracoronary boluses of LTD4 (0.3, 1.0 and 3.0 micrograms) during verapamil infusion into the same vessel caused dose-dependent decreases in CBF identical to those observed when LTD4 was injected during control infusion. ECGs showed myocardial ischemia during severe flow reduction after high dose intracoronary LTD4 (3.0 or 10.0 micrograms). When the same LTD4 doses were injected during intracoronary verapamil, electrocardiographic changes did not occur despite similar decreases in CBF. The capacity of verapamil to prevent LTD4-induced ischemia may be caused by higher residual CBF after LTD4 even though the magnitude of LTD4-induced CBF decrement was unaltered. LTD4-induced coronary constriction seems to be mediated by a mechanism unrelated to calcium entry channels blocked by verapamil, nifedipine or diltiazem.