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The diversity of racial/ethnic representation in the health services and policy research (HSPR) workforce plays a crucial role in addressing the health needs of underserved populations. We assessed changes (between 2012 and 2022) in the racial/ethnic composition of students and faculty from departments of Health Policy & Management (HPM) and Health Education & Behavioral Sciences (HEBS) among the Association of Schools and Programs of Public Health member institutions. We analyzed annual data from over 40 institutions that reported student and faculty data in 2012 and 2022 within each department. Racial/ethnic populations included American Indian/Alaska Native (AI/AN), Asian, Hispanic, Native Hawaiian/Pacific Islander (NH/PI), Black, White, Unknown, and Multiracial. We conducted analyses by department and examined racial/ethnic composition by student status, degree level, faculty rank, and tenure status. We found statistically significant increases in Black assistant professors (HPM and HEBS) and tenured faculty (HPM), Hispanic graduates and tenure-track faculty (HPM), Asian professors (HPM: full and tenured, HEBS: associate and tenured), and Multiracial students and graduates (HPM and HEBS). Statistically significant decreases were observed in White professors (HPM: assistant and full, HEBS: all ranks) and tenure-track faculty (HPM and HEBS), AI/AN associate professors and tenured faculty (HEBS), Hispanic associate professors (HPM), Asian assistant professors (HEBS), and NH/PI students (HPM and HEBS). Our findings highlight the importance of increasing racial/ethnic representation. Strategies to achieve this include facilitating workshops to raise awareness about the structural barriers encountered by Hispanic faculty, providing research support, evaluating promotion processes, establishing more pathway programs, and fostering interdisciplinary academic environments studying AI/AN or NH/PI populations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The relationship between the onset of the COVID-19 pandemic and interest in master of public health (MPH) programs is unknown. We examined trends in MPH application rates for 31 MPH concentrations and specifically for the MPH concentration in epidemiology and differences by race and ethnicity before and after the onset of the COVID-19 pandemic., Methods: We constructed a quasi-experimental design to examine trends in MPH application rates from academic years 2015-2016 through 2022-2023 by using Centralized Application Service for Schools and Programs of Public Health data. We used an interrupted time-series analysis to test whether application rates surged after the pandemic's onset (academic years 2019-2020 through 2020-2021) and whether this increase persisted during the pandemic (academic years 2020-2021 through 2022-2023). We fit models for the overall sample, a combined racially and ethnically minoritized sample, each racial and ethnic group separately, and a non-US citizen sample., Results: The pandemic's onset correlated with an immediate increase in application rates across most samples: overall (38%) and among American Indian/Alaska Native/Native Hawaiian/Pacific Islander (91%), Asian (35%), Black (42%), Hispanic (60%), multiracial (30%), racially and ethnically minoritized (44%), and White (53%) samples. However, this trend was not sustained; application rate trends during the pandemic were significantly lower than prepandemic trends. Application rate trends for all MPH concentrations and the MPH in epidemiology concentration among non-US citizens were significantly higher during the pandemic than prepandemic., Conclusions: Our results highlight the need for innovative strategies to sustain MPH degree interest and a diverse applicant pool., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: This study was designed to determine whether a virtual, self-care activity improved knowledge and confidence in third-year student pharmacists., Educational Activity and Setting: Third-year student pharmacists (n = 386) from three institutions participated in the virtual self-care simulation during their respective practice laboratory course. A pre- and post-assessment collected 10 knowledge and five confidence questions, self-reported on 0-100 scale, mapped to learning outcomes and pharmacy standards. Responses for participants who provided consent and had linked assessments were analyzed. Additionally, students participated in a perception assessment following the simulation with the post-assessment. Each knowledge question was scored as binary (correct/incorrect), presented as percentage, and significance identified with a McNemar's test. Total knowledge score and confidence changes were presented as means with standard deviations and significance with a paired t-test. Student perceptions were presented as frequencies and percentages., Findings: Total knowledge assessment demonstrated a significant improvement (p < 0.001) for the entire cohort of 198 study participants. Upon additional analysis, a single institution led the cohort to significant increase, with variable improvement and significance for each individual question. Confidence improved for the entire cohort of students and at each institution individually. The students perceived the virtual self-care activity favorably., Summary: The third-year student virtual self-care activity improved knowledge and confidence with varying significance between institutions. Future studies will focus on the impact of continued reinforcement of self-care activities on student growth in knowledge and confidence., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To analyze the current public health labor market for bachelor's-level graduates., Methods: Public health-related job postings ( N  = 365) from across the United States were collected from an online job portal, Indeed.com, from November 7-14, 2022. Job titles, organization type, degree requirements, work experience, job location, and preferred skills for bachelor's-level public health positions were analyzed., Results: Thirty-one job titles were identified. Approximately one-third (32.33%) of postings were from the Northeastern US; 23.56% were from the Southeastern region. Thirty-five job skill categories were identified. Most jobs (92.33%) required oral and written communication skills, and 85.21% specified educational skills for public health promotion. Cultural competency, project management, and case management abilities were also highly sought., Conclusion: This study revealed the needs of the public health workforce and bolstered the case that public health degree-seekers should be equipped with a set of strategic skills applicable to a range of multisectoral and multidisciplinary public health jobs., Policy Implications: Given the rapid changes in the field of public health, ongoing analysis of the labor market benefits educators, employers, and policymakers alike., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kedia, Entwistle, Lee, Magaña, Burke and Joshi.)

Background: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education., Methods: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers., Results: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results., Conclusion: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities., (© 2023. The Author(s).)

The lack of diversity among the environmental health sciences (EHS) workforce has been an ongoing concern. However, limited research exists on the racial and ethnic composition of EHS students and faculty over time. We analyzed 2011 and 2021 data on EHS students, graduates, and faculty to compare changes in the racial and ethnic composition among Association of Schools and Programs of Public Health-member institutions. Among the institutions that reported data in both years, we observed significant proportion increases among Hispanic enrolled students (overall and master's: both P  = .01), Multiracial enrolled students and graduates (overall: both P  < .05, master's level: both P  < .05), and Asian tenured professors ( P  = .01). Significant decreases were observed among Unknown enrolled students (overall: P  = .01, master's level: P  < .001), Unknown master's level graduates ( P  = .01), AI/AN enrolled students (overall and master's: both P  < .05), and White full professors ( P  < .001) and tenured faculty ( P  < .001). Despite these findings, no substantial change existed among the other racial and ethnic groups. More efforts are needed to recruit, train, and promote racial and ethnic minorities who can leverage their lived experiences to provide novel solutions to environmental challenges., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: Older adults are susceptible to cognitive declines that may limit independence. Though neuropsychologists opine about risk of functional decline, the degree to which cognitive testing and in-office simulations approximate everyday behavior is unclear. We assessed the complementary utility of cognitive testing and the face-valid Medication Management Ability Assessment (MMAA) to predict medication management among older adults., Method: This was a retrospective study of 234 older adults (age = 72 ± 7.7 years; 59% women) who completed the MMAA during outpatient neuropsychological evaluations. Based on comprehensive clinical assessment, most participants ( n = 186) were independent in medication management, while 48 received assistance. Demographically adjusted composite scores were derived for attention/processing speed (A/PS), executive functioning (EF), visuospatial/constructional ability (VC), language, and memory domains. Univariate differences in cognition were examined across Assisted versus Independent groups. Logistic regression assessed which cognitive domains independently predicted group status. The incremental value of the MMAA was assessed, holding uniquely associated cognitive test scores constant., Results: Those receiving assistance with medication management performed worse across all neurocognitive domains and the MMAA compared with independent counterparts. EF was the only unique cognitive predictor of medication management status. When modeled alone, EF and MMAA performance correctly classified 79.5% and 80.8% of cases, respectively. When modeled together, both were independently associated with medication management status and correctly classified 83.3% of cases., Conclusions: EF uniquely predicted medication management status beyond other cognitive domains. The MMAA provided complementary predictive utility. Concurrent interpretation of executive functioning and MMAA performance is advised when assessing older adults suspected of medication mismanagement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The visualization of intracranial epidermoid tumors is often limited by difficulties associated with distinguishing the tumor from the surrounding cerebrospinal fluid using traditional computed tomography (CT) or magnetic resonance imaging (MRI) modalities. This report describes our experience using CT cisternography to visualize intracranial epidermoid tumors in three illustrative cases. CT cisternography of the epidermoid tumor provides more clarity and precision compared to traditional neuroimaging modalities. We demonstrate the feasibility of using CT cisternography to produce high-resolution images with well-defined tumor margins that can be used effectively for precise SRS treatment planning., Competing Interests: Declaration of Competing Interest EB is employed by Superior Medical Experts. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The rise of neurointerventional devices has created a demand for guide systems capable of navigating to the carotid artery consistently regardless of tortuosity. The shift toward large distal access catheters (DACs) and desire for greater trackability have inspired the creation of flexible, supportive, large-lumen long guiding sheaths. Recently, the Ballast long guiding sheath was introduced to provide stability and flexibility while navigating neurointerventional devices through tortuous intracranial anatomy. Objective: To report our experience using the Ballast long guiding sheath in a series of patients undergoing a variety of neuroendovascular procedures. Methods: We retrospectively identified all patients who underwent neuroendovascular treatment with a long guiding sheath were selected from a prospectively maintained endovascular database from January 2019 to November 2019. Baseline clinical characteristics and procedural details were collected. Results: A total of 68 patients were included, mean patient age 67.6 ± 13.6 years. Of the patients treated, 52.9% (36/68) presented with stenosis, 25% (17/68) with aneurysms, 13.2% (9/68) with stroke or emboli, 1.5% (1/68) with a tumor, 1.5% (1/68) with an arteriovenous fistula (AVF), and 4.4% (3/68) with a carotid web. Of the patients with stenosis, 20/36 (55.6%) were extracranial, and 16/36 (44.4%) were intracranial. The Ballast long guiding sheath was used to deliver treatment devices for stenting (37/68, 54.4%), flow diversion (12/68, 17.6%), mechanical thrombectomy (8/68, 11.8%), endovascular coiling (5/68, 7.4%), liquid embolization (3/68, 4.4%), balloon angioplasty (2/68, 2.9%), and balloon angioplasty with stenting (1/68, 1.5%). No Ballast-related complications or adverse events were encountered. Conclusions: We demonstrate the feasibility of the Ballast long guiding sheath to successfully deliver modern neurointerventional treatment devices through tortuous anatomy., Competing Interests: AH serves as a consultant and speaker for GE Healthcare, Medtronic, Stryker, Microvention, Penumbra, Balt USA, and Genentech. EB contracts with Superior Medical Experts. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hassan, Burke, Monayao and Tekle.)

Case Presentation: A 67-year-old woman presented to her primary physician with a year of periumbilical abdominal discomfort with diarrhea, bloating, and unintentional weight loss. While undergoing workup for the abdominal pain, she presented to the ED with dyspnea that worsened over a few weeks. She had no associated chest pain, lower extremity edema, fevers, or chills, but endorsed orthopnea. The patient's medical history included hypothyroidism and diabetes mellitus. Her family history was significant for coronary disease in her father and hypertension in her mother. She had no recent travel; she is a nonsmoker and rare alcohol drinker. She worked in administration., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1-7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.

Introduction: This clinical trial aimed to determine whether in-car video feedback about unsafe driving events (UDE) to cognitively impaired older drivers and family members leads to a reduction in such driving behaviors., Methods: We randomized 51 cognitively impaired older drivers to receive either (1) a weekly progress report with recommendations and access to their videos, or (2) video monitoring alone without feedback over 3 months., Results: UDE frequency/1000 miles was reduced by 12% in feedback (rate ratio [RR] = 0.88, 95% confidence interval [CI] = .58-1.34), while remaining constant with only monitoring (RR = 1.01, 95% CI = .68-1.51). UDE severity/1000 miles was reduced by 37% in feedback (RR = 0.63, 95% CI = .31-1.27), but increased by 40% in monitoring (RR = 1.40, 95% CI = .68-2.90). Cognitive impairment moderated intervention effects ( P  = .03) on UDE frequency., Discussion: Results suggest the potential to improve driving safety among mild cognitively impaired older drivers using a behavior modification approach aimed at problem behaviors detected in their natural driving environment., Competing Interests: None of the authors have any conflicts of interest to disclose related to this research or the manuscript., (© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Objectives. To improve understanding of the future public health workforce by analyzing first-destination employment outcomes of public health graduates. Methods. We assessed graduate outcomes for those graduating in 2015-2018 using descriptive statistics and the Pearson χ 2 test. Results. In our analysis of data on 53 463 graduates, we found that 73% were employed; 15% enrolled in further education; 5% entered a fellowship, internship, residency, volunteer, or service program; and 6% were not employed. Employed graduates went to work in health care (27%), corporations (24%), academia (19%), government (17%), nonprofit (12%), and other sectors (1%). In 2018, 9% of bachelor's, 4% of master's, and 2% of doctoral graduates were not employed but seeking employment. Conclusions. Today's public health graduates are successful in finding employment in various sectors. This new workforce may expand public health's reach and lead to healthier communities overall. Public Health Implications. With predicted shortages in the governmental public health workforce and expanding hiring because of COVID-19, policymakers need to work to ensure the supply of public health graduates meets the demands of the workforce.

Purpose: Flow diverters (FD) have poor radiopacity, challenging visualization of deployment and vessel wall apposition with conventional neuroimaging modalities. We evaluated a novel cone beam computed tomography (CT) imaging technique that allows virtual dilution (VD) of contrast media to facilitate workflow and ensure accurate assessment of FD wall apposition., Methods: We retrospectively evaluated all patients treated for intracranial aneurysms with FD at our institution between November 2018 and November 2019. Undiluted injected dual cone beam CT acquisitions performed post-stenting were displayed with VD software (GE Healthcare). The resulting images were compared with conventional two-dimensional (2D) digital subtraction angiography (DSA) images. Two neurointerventionalists (Reader 1 and Reader 2, (R1, R2)) independently assessed FD deployment and wall apposition. Confidence in the diagnosis, inter-reader agreement, and X-ray exposure were assessed., Results: A total of 27 cases were reviewed. FD deployment and wall apposition scores were 4.2 ± 1.0 (R1) and 4.0 ± 1.1 (R2) for DSA and 3.7 ± 1.2 (R1) and 4.1 ± 1.0 (R2) for VD. Confidence in the diagnosis was improved with VD, with scores of 3.7 ± 0.7 (R1) and 4.0 ± 0.7 (R2) using DSA and 4.9 ± 0.2 (R1) and 4.9 ± 0.2 (R2) using VD (P < 0.001). Inter-reader agreement using 2D DSA was improved from moderate (0.49324) to good (0.7272) (P < 0.0001). There were no significant differences in inter-reader agreement in the deployment assessment (P = 0.68) or dose-area product (P = 0.54) between techniques., Conclusion: VD imaging with dual cone beam CT enables accurate assessment of FD wall apposition after deployment with greater confidence and improved inter-reader agreement versus conventional 2D DSA alone, with comparable X-ray exposure.

Purpose: To provide a comprehensive review to determine whether there is a class effect among angiotensin receptor blockers (ARBs) in relation to serum uric acid., Summary: A literature search was conducted and 8 articles were identified for inclusion in this review. In the studies reviewed, candesartan and valsartan were shown to have either a neutral or negative effect on serum uric acid. Azilsartan was shown to have a negative impact on serum uric acid while eprosartan appeared to have no impact on serum uric acid levels. Irbesartan demonstrated either a neutral or positive effect on serum uric acid while losartan exhibited a positive effect., Conclusion: The available data indicate that the reduction of serum uric acid is not a class effect of ARBs. Of the available agents, only losartan has clear evidence of its ability to lower serum uric acid. For patients with high blood pressure and elevated serum uric acid, losartan should be considered as a first-line agent with irbesartan as an alternative when appropriate.

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer's dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer's disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and those without evidence of cerebral amyloidosis (CN/A+ and CN/A-) using a global positioning system (GPS) datalogger. Thirty-three drivers (aged 60+ years) were studied over 3 months. G-force triggered video events captured instances of near-misses/collisions, traffic violations, risky driver conduct, and driving fundamentals. GPS data were sampled every 30 s and all instances of speeding, hard braking, and sudden acceleration were recorded. For the early AD participants, video capture identified driving unbelted, late response, driving too fast for conditions, traffic violations, poor judgment, and not scanning intersections as the most frequently occurring safety errors. When evaluating driving using the GPS datalogger, hard breaking events occurred most frequently on a per trip basis across all three groups. The CN/A+ group had the lowest event rate across all three event types with lower instances of speeding. Slower psychomotor speed (Trail Making Part A) was associated with fewer speeding events, more hard acceleration events, and more overall events. GPS tracked instances of speeding were correlated with total number of video-captured near-collisions/collisions and driving fundamentals. Results demonstrate the utility of electronic monitoring to identify potentially unsafe driving events in symptomatic and preclinical AD. Results suggest that drivers with preclinical AD may compensate for early, subtle cognitive changes by driving more slowly and cautiously than healthy older drivers or those with cognitive impairment. Self-regulatory changes in driving behavior appear to occur in the preclinical phase of AD, but safety concerns may not arise until symptoms of cognitive impairment emerge and the ability to self-monitor declines., (Copyright © 2020 Davis, Babulal, Papandonatos, Burke, Rosnick, Ott and Roe.)

Objective: Qualitative research has identified personal costs and benefits for peer supporters associated with their role; however, quantitative evidence is sparse. This study used quantitative methods to explore relationships in experiences of providing peer support with constructs of empowerment, hope, recovery, quality of life and internalised stigma. Differences were examined for those in statutory versus non-statutory services; who had themselves received peer support versus those who had not and who identified having had negative experiences in clinical teams versus those without such experiences., Methods: A cross-sectional online and postal survey was undertaken in tandem with a linked consensus study. In all, 147 peer supporters were recruited from a variety of organisations across the United Kingdom. Validated questionnaires were used to examine constructs. Instruments created for the study measured peer support experiences, and personal costs and benefits involved. Correlations were calculated and results informed further regression analysis. Chi-square tests and independent samples t -tests tested group differences., Results: Peer supporters indicated they experienced almost twice as many role-related personal benefits than personal costs. Benefits included improvements to mental health and well-being, reduced use of services, increased social functioning and development of skills. Total number of personal costs experienced was significantly negatively related to peer supporters' empowerment and quality of life. There were no significant differences between the groups examined., Conclusions and Implications for Practice: An accumulation of personal costs may result in reduced quality of life; however, costs can be minimised by organisations. Limitations of the research are discussed and recommendations for future research are made including the need for longitudinal research.

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A large pneumothorax was detected on chest x-ray film in a 41-year-old woman. She declined recommendations for evacuation of the air trapped in her right chest. The condition spontaneously resolved during 3 months after being detected.

Background: Studies have associated anti-HLA antibodies detected by panel-reactive antibody (PRA) with increased risk for rejection and transplant coronary artery disease (TCAD) in adults, but the role of PRAs in monitoring immunologic status after pediatric cardiac transplantation has not been described., Methods: We reviewed post-transplant PRAs in 96 pediatric heart recipients. PRAs were performed concurrently with endomyocardial biopsy and if rejection was suspected. The presence of anti-HLA IgG antibodies was defined as >10% reactivity. Pre-transplant variables, including age, race, gender, pre-transplant PRAs and presence of a mechanical assist device, were correlated with post-transplant PRAs. Outcome variables included rejection history, TCAD incidence and survival., Results: The mean age of patients was 9.0 +/- 6.8 years. A mean of 8.1 +/- 5.3 PRAs were measured over a follow-up period of 4.8 +/- 2.7 years. There was a mean of 0.55 +/- 0.71 rejection events per patient-year, and TCAD was detected in 19 (22%) patients. Nineteen patients (20%) had anti-HLA Class I antibodies and 37 (39%) had Class II antibodies detected after transplant. There was no association between Class I antibodies and survival, TCAD or rejection. Class II antibodies were associated with worse survival and a decreased time-free of TCAD. Class II antibodies were also associated with rejection at the time of measurement (sensitivity 17%, specificity 94%) and for the ensuing 3 months (sensitivity 12%, specificity 94%)., Conclusions: Class II anti-HLA antibodies correlate with worse patient outcomes and rejection episodes after pediatric cardiac transplant. A low sensitivity precludes use as a sole diagnostic tool, but post-transplant PRAs may be an important adjunct in a multi-faceted algorithm to assess immunologic status.

Background: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV., Methods: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site., Results: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population., Conclusions: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.

Background: Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation., Methods and Results: A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA-DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls., Conclusions: IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.

The success of calcium phosphate (CaP) coatings used to accelerate initial bone growth onto dental implants can vary depending on the CaP phases present in the coating. In this study, the effect of CaP coating crystal structure and morphology on dissolution rates was investigated. RF magnetron-sputtered CaP coatings (NTC) were compared to a less strained coating (HTC) obtained from heat treatment of sputtered samples at 550 degrees C. Coating strain differences were apparent in XRD spectra where hydroxyapatite-like planes shifted by 0.5 degrees 2theta and 0.05 degrees 2theta for the NTC and HTC coatings, respectively. HTC XRD peak widths were broader than NTC peak widths, indicating smaller crystals or grain sizes. These differences in grain size were corroborated by imaging with scanning probe microscopy. NTC coatings dissolved at a 300% faster rate than HTC coatings. A major factor contributing to this kinetic effect was the level of strain in both coatings. These results suggest an alternate design for CaP coatings can be obtained through the manipulation of coating strain. Using this approach, delivery of different ionic gradients from CaP coatings to surrounding tissue environments can be obtained from surfaces having similar chemistries.

Background: Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without inducing global immunosuppression., Methods: We randomly assigned 55 nonsensitized patients undergoing a first cardiac transplantation to receive either induction therapy with daclizumab (1.0 mg per kilogram of body weight), given intravenously within 24 hours after cardiac-transplantation surgery and every two weeks thereafter, for a total of five doses, or generalized immunosuppressive therapy. Concomitant immunosuppression was achieved in both groups with cyclosporine, mycophenolate mofetil, and prednisone. The primary end points were the incidence and severity of acute rejection, and the length of time to a first episode of biopsy-confirmed rejection., Results: Of the 55 patients in the study, 28 were randomly assigned to receive daclizumab and 27 served as the control group. During induction therapy, the mean frequency of acute rejection episodes (defined as a histologic grade of 2 or higher according to the classification of the International Society of Heart and Lung Transplants) was 0.64 per patient in the control group and 0.19 per patient in the daclizumab group (P=0.02). Acute rejection developed in 17 of 27 patients in the control group (63 percent), as compared with 5 of 28 patients in the daclizumab group (18 percent; relative risk, 2.8; 95 percent confidence interval, 1.1 to 7.4; P=0.04). Throughout follow-up, there were nine patients with episodes of acute rejection of histologic grade 3 in the control group, as compared with two in the daclizumab group (P= 0.03), and the time to a first episode of rejection was significantly longer in the daclizumab group (P=0.04). There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer during follow-up., Conclusions: Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.

Background: Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist devices (LVADs) are currently under investigation as permanent therapy for end-stage heart failure, but long-term successful device implantation is limited because of a high rate of serious infections. To examine the relation between LVAD-related infection and host immunity, we investigated immune responses in LVAD recipients., Methods: We compared the rate of candidal infection in 78 patients with New York Heart Association class IV heart failure who received either an LVAD (n=40) or medical management (controls, n=38). Fluorochrome-labelled monoclonal antibodies were used in analyses of T-cell phenotype. Analysis of T-cell function included intradermal responses to recall antigens and proliferative responses after stimulation by phytohaemagglutinin, monoclonal antibodies to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vivo by annexin V binding, and confirmed the result by assessment of DNA fragmentation. Activation-induced T-cell death was measured after T-cell stimulation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation. Between-group comparisons were by Kaplan-Meier actuarial analysis and Student's t test., Findings: By 3 months after implantation of LVAD, the risk of developing candidal infection was 28% in LVAD recipients, compared with 3% in controls (p=0.003). LVAD recipients had cutaneous anergy to recall antigens and lower (<70%) T-cell proliferative responses than controls after activation via the T-cell receptor complex (p<0.001). T cells from LVAD recipients had higher surface expression of CD95 (Fas) (p<0.001) and a higher rate of spontaneous apoptosis (p<0.001) than controls. Moreover, after stimulation with antibodies to CD3, CD4 T-cell death increased by 3.2-fold in LVAD recipients compared with only 1.2-fold in controls (p<0.05)., Interpretation: LVAD implantation results in an aberrant state of T-cell activation, heightened susceptibility of CD4 T cells to activation-induced cell death, progressive defects in cellular immunity, and increased risk of opportunistic infection.

Background: Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied., Methods and Results: The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P=0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection., Conclusions: These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

Background: Transplant-related coronary-artery disease (TCAD) develops frequently in cardiac-allograft recipients, and limits long-term survival. We examined the relation between this disorder and cumulative frequency of high-grade rejection, and investigated whether concomitant use of three immunological factors at the time of a low-grade endomyocardial biopsy can predict progression to high-grade rejection., Methods: We investigated the relation between the cumulative annual frequency of high-grade rejection and TCAD in 198 recipients of cardiac transplantation between 1992 and 1996 by means of Kaplan-Meier actuarial life-tables. Endomyocardial biopsy, lymphocyte-growth assays, and anti-HLA antibody measurements were compiled over 12 months in 102 patients during their first post-transplant year. We calculated predictive values for high-grade rejection within 90 days by chi2, Kaplan Meier survival curves, and by multivariable logistic regression analyses., Findings: We found a direct correlation between cumulative annual frequency of rejection and TCAD onset with highest risk in those with more than 0.75 rejections per year (p=0.0002). After a low-grade endomyocardial biopsy (0 or 1A), one or more donor-recipient HLA-DR matches protected against high-grade rejections (p<0.001). Among individuals with one or two DR matches, the negative predictive value for progression from a low-grade biopsy to a high-grade rejection was 87% in the presence of a negative lymphocyte-growth assay. Among individuals with no DR matches, the presence of either a positive lymphocyte-growth assay or IgG anti-major-histocompatibility complex (MHC) class II antibodies was independently associated with high probability of progression to rejection (64% and 66%, respectively, p<0.0005). When both assays were positive, concomitantly with a low-grade endomyocardial biopsy, the positive predictive value for progression to a high-grade rejection was 86% (p<0.0001). For endomyocardial-biopsy grades 1B or 2, a positive lymphocyte-growth assay alone was associated with high-grade rejection in 100% of cases., Interpretation: Use of an algorithm combining three immunological factors at the time of a low-grade endomyocardial biopsy enables prospective stratification of cardiac transplant recipients into risk categories for progression to high-grade rejection. Low-risk individuals require fewer biopsies, moderate-risk individuals require an ongoing schedule of surveillance biopsies, and high-risk individuals require rational organisation of interventional strategies aimed at preventing rejection. Additional predictive factors are needed to identify moderate-risk individuals who will progress to rejection. Ultimately, successful intervention may have an impact on the subsequent complication of TCAD.

The behavior of the keratinocyte during the initial stages of cutaneous wound repair has been the subject of intense investigation. Most of these studies have focused on the lateral edges of wounds as the source of activated keratinocytes. Less attention has been directed towards elucidating the role of the appendageal structures as sources of keratinocytes for re-epithelialization, particularly the sweat apparatus. Surgical wounds of specific depths were created in pig skin, above and below hair follicles, and wound healing was allowed to take place in a setting in which lateral ingrowth of keratinocytes by migration was prevented. In this manner, all re-epithelialization occurred from residual appendageal structures. In those wounds where only sweat gland elements remained, an epithelium formed that had clinical, morphologic, and protein electrophoretic features closer to palmar/plantar or mucosal-like epithelia. In contrast, wounds that retained elements of the hair follicle healed faster and the resultant epithelium clinically, morphologically, and biochemically resembled the surrounding nonwounded epidermis. These findings establish that the sweat apparatus is capable of re-epithelializing the skin surface after a major cutaneous wound, but may not be capable of mimicking the epidermis.

Plasma spray and high velocity oxy-fuel (HVOF) techniques produce coatings with varying composition and amounts of amorphous and crystalline phases. For coatings containing greater amorphous phases, a higher release of calcium ions is evident when samples are placed in Hank's calcium-free balanced salt solutions. Calcium is released from the amorphous phases in the coating, a conclusion that is supported by x-ray powder diffraction (XRD) results. Ion beam sputtering and RF magnetron sputtering under lower energy conditions produce amorphous coatings that will dissolve in a very short time period. When heat treated, crystalline phases are produced in the coatings. Heat-treated coatings are significantly more stable than the amorphous coatings. The dissolution rates of both amorphous and crystalline coatings produced by RF magnetron sputtering have been measured under constant solution conditions at pH 6.50. No reprecipitation is possible under these conditions. The amorphous coating dissolved at a significantly higher rate than the heat-treated coating. Reprecipitation of calcium phosphate onto amorphous coatings is possible in a physiological pH solution. Under these conditions, the dissolution rate of the amorphous coating is four times slower than at the pH 6.50 conditions.

A constant composition (CC) method was used to compare the influence of statherin-like N-terminal 5-residue fragments having different amino acids in the terminal position on hydroxyapatite (HAP) growth and dissolution. The CC experiments were done in solutions containing 4.00 x 10(-4) mol/l calcium and 2.40 x 10(-4) mol/l phosphate. The solutions used in the crystallization studies were supersaturated only with respect to HAP (pH = 7.40, sigma HAP = 3.60). The CC dissolution studies were done in solutions undersaturated with respect to HAP (pH = 6.00; sigma HAP = -0.39). The HAP mineralization and demineralization processes were markedly inhibited by the negatively charged pentapeptides. Those containing a phosphorylated terminal residue inhibited dissolution to a greater extent than the native statherin fragment having aspartate as the N-terminal residue. Strong dependencies of the degree of inhibition of growth and dissolution reaction rates on the extents of reaction were noted. As the reactions proceeded, the rate inhibition decreased in the case of crystal growth and increased for dissolution.

The 12-month clinical outcomes of nursing home patients who underwent videofluoroscopic swallowing evaluation was determined. A retrospective review of 40 patients in a teaching nursing home who had videofluoroscopic swallowing studies from 1987 through 1989 was performed. Clinical outcomes measured included feeding tube placement, rehospitalization within 1 year, prolonged nursing home stay (> 6 months), pneumonia, and pneumonia death. It was determined if outcomes were associated with the presence of aspiration on videofluoroscopy and subsequent feeding tube placement. In the 12-month follow-up period, 17 of 40 patients (43%) who underwent videofluoroscopic swallowing evaluation developed pneumonia and 18 of 40 (45%) died. Twenty-two patients demonstrated aspiration on videofluoroscopy. Increased rehospitalization was the only outcome measure that was associated with the presence of aspiration on videofluoroscopy (p < or = 0.05). Of 22 patients with aspiration, 15 had feeding tubes placed. This group had a higher rate of pneumonia (p < or = 0.05) and pneumonia death (p < or = 0.05) compared with the 7 patients with aspiration who did not receive feeding tubes. Patients with nasogastric tubes had a higher death rate (7/9) than patients with gastrostomy tubes (2/8; p < or = 0.05), but similar rates of rehospitalization and pneumonia. Nursing home patients who underwent video-fluoroscopic swallowing evaluation had poor clinical outcomes at 12 months, regardless of their test results.(ABSTRACT TRUNCATED AT 250 WORDS)

An atypical oral presentation of herpes simplex virus infection in a 49-year-old woman after orthotopic liver transplantation is reported. Clinically, the differential diagnosis included chronic hyperplastic candidiasis, nodular leukoplakia of undetermined etiology, and malignant neoplasm. An excisional biopsy revealed herpesvirus infection, and immunoperoxidase staining confirmed herpes simplex virus infection. This report describes the clinical and histologic appearance of these lesions and the course and treatment of the patient.

Primary human dermal fibroblasts isolated from the medial aspect of the proximal forearm of young and old donors were compared for the expression of interstitial collagenase, 72 kDa type IV collagenase, the tissue inhibitor of metalloproteinase type 1, and pro-alpha 2 (I) collagen mRNA at basal levels and after stimulation with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate. Higher basal and induced steady-state mRNA levels of interstitial collagenase were found in the cells from older donors. Ratios of basal and induced steady-state mRNA levels of interstitial collagenase to pro-alpha 2 (I) collagen, and interstitial collagenase to the tissue inhibitor of metalloproteinases type 1 were also higher in the cells from older donors. Seventy-two kiloDalton type IV collagenase and pro-alpha 2 (I) collagen mRNA showed similar levels of expression in the cells from young and old donors and were not altered by treatment with 12-O-tetradecanoyl-phorbol-13-acetate. Transient transfection assays with the interstitial collagenase promoter linked to a reporter gene showed increased activity of the reporter in cell strains with high interstitial collagenase mRNA levels. Mobility shift assays demonstrated increased binding activity to the specific 12-O-tetradecanoyl-phorbol-13-acetate response element in nuclear extracts from the cell strains with higher induced collagenase mRNA levels and higher reporter gene activity. These findings are consistent with the observed phenotype of interstitial collagenase and its specific tissue inhibitor in the senescent fibroblast aging model.

The opossum kidney (OK) cell was used as a model to test the hypothesis that estrogen directly affects proximal renal tubular epithelial cells. To demonstrate the expression of estrogen receptor in OK cells, we developed an approach using reverse transcription and the polymerase chain reaction. Analysis of the DNA amplified with nested primers revealed the predicted size fragment and restriction enzyme digestion products. To demonstrate the functional effects of estrogen, OK cells at confluence were preincubated in serum-free medium for 7-10 days with or without 17 beta-estradiol. Bovine PTH(1-34) (bPTH(1-34)) then stimulated a dose-dependent intracellular accumulation of cAMP that was maximal after 1 min and then gradually declined. Cyclic AMP in the medium slowly increased over 60 min. Preincubation with 17 beta-estradiol did not affect cell proliferation as measured by total protein content but caused an inhibition of bPTH(1-34)-stimulated intracellular cAMP accumulation that was maximal at 10(-11) M 17 beta-estradiol (71 +/- 3% control, p less than .001). bPTH(1-34) also increased cAMP release into the medium, an effect maximal using 10(-10) M 17 beta-estradiol (118 +/- 3% control, p less than .001). Preincubation with the inactive isomer 17 alpha-estradiol caused no changes in cAMP accumulation or release. Coincubation with the antiestrogen tamoxifen blocked the effects of 17 beta-estradiol. Sodium-dependent phosphate transport was: (1) inhibited by 2-h incubations with 10(-8) or 10(-10) M bPTH(1-34) and not affected by preincubation with 17 beta-estradiol, and (2) not inhibited by a 20-min incubation with 10(-8) M bPTH(1-34) unless cells were preincubated with 10(-8) M 17 beta-estradiol, suggesting that any possible effects of estrogen on phosphate transport are not directly mediated by changes in cAMP. These studies demonstrate the presence of estrogen receptor mRNA in OK cells as well as direct and specific effects of physiologic concentrations of estrogen on cAMP accumulation in these cells. This system may be a good model for further study of estrogen and PTH effects on the kidney.

Senescent human fibroblasts produce larger fibronectin molecules with altered binding properties. To determine if this change could involve alternative splicing of fibronectin precursor mRNA, we developed an approach using reverse transcription and the polymerase chain reaction to study fibronectin mRNA splicing at each of the three alternatively spliced regions. Two of the three regions showed changes with in vitro passage incorporation of the ED-A region increased 8 fold.

Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome.