Aberrant soluble epoxide hydrolase and oxylipin levels in a porcine arteriovenous graft stenosis model.

Synthetic arteriovenous grafts (AVGs) used for hemodialysis frequently fail due to the development of neointimal hyperplasia (NH) at the vein-graft anastomosis. Inflammation and smooth-muscle cell (SMC) and myofibroblast proliferation and migration likely play an important role in the pathogenesis of NH. Epoxyeicosatrienoic acids (EETs), the products of the catabolism of arachidonic acid by cytochrome P450 enzymes, possess anti-inflammatory, antiproliferative, antimigratory and vasodilatory properties that should reduce NH. The degradation of vasculoprotective EETs is catalyzed by the enzyme, soluble epoxide hydrolase (sEH). sEH upregulation may thus contribute to NH development by the enhanced removal of vasculoprotective EETs. In this study, sEH, cytochrome P450 and EETs were examined after AVG placement in a porcine model to explore their potential roles in AVG stenosis. Increased sEH protein expression, decreased P450 epoxygenase activity and dysregulation of 5 oxylipin mediators were observed in the graft-venous anastomotic tissues when compared to control veins. Pharmacological inhibitors of sEH decreased the growth factor-induced migration of SMCs and fibroblasts, although they had no significant effect on the proliferation of these cells. These results provide insights on epoxide biology in vascular disorders and a rationale for the development of novel pharmacotherapeutic strategies to prevent AVG failure due to NH and stenosis.

A Scoping Review of Diagnosis of Autism Spectrum Disorder in Primary Care.

INTRODUCTION: This scoping review was performed to collect, examine, and present literature on interventions promoting the diagnosis of Autism Spectrum Disorder (ASD) in U.S. primary health care settings. METHOD: The literature searched was from 2011-2022, in the English language, in PubMed, CINAHL, Psych INFO, Cochrane, and Web of Science, for persons with autism or ASD aged ≤ 18 years. RESULTS: Six studies met the search criteria, including a quality improvement project, a feasibility study, a pilot study, and three primary care provider (PCP) intervention trials. Measured outcomes included: accuracy of diagnosis (n = 4), practice change maintenance (n = 3), time to diagnosis (n = 2), specialty clinic appointment wait time (n = 1), PCP comfort making ASD diagnosis (n = 1), and increased ASD diagnosis (n = 1). DISCUSSION: Results inform future implementation of PCP ASD diagnosis for the most obvious cases of ASD and research evaluating PCP training, using longitudinal measures of PCP knowledge of ASD and intention to diagnose.

PDGF-induced proliferation in human arterial and venous smooth muscle cells: molecular basis for differential effects of PDGF isoforms.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of arterial atherosclerosis and venous neointimal hyperplasia. We examined the effects of PDGF isoforms on smooth muscle cells (SMCs) from arterial and venous origins in order to further understand the differential responsiveness of these vasculatures to proliferative stimuli. Serum-starved human arterial and venous SMCs exhibited very different proliferative responses to PDGF isoforms. Whereas, proliferation of arterial SMCs was strongly stimulated by PDGF-AA, venous SMCs showed no proliferative response to PDGF-AA, but instead demonstrated a significantly greater proliferative response to PDGF-BB than arterial SMCs. Part of this difference could be attributed to differences in PDGF receptors expression. There was a 2.5-fold higher (P < 0.05) density of PDGF receptor-α (PDGF-Rα) and a 6.6-fold lower (P < 0.05) density of PDGF-Rß expressed on arterial compared to venous SMCs. Concomitant with an increased proliferative response to PDGF-AA in arterial SMCs was a marked PDGF-Rα activation, enhanced phosphorylation of ERK1/2 and Akt, a transient activation of c-Jun NH2-terminal kinase (JNK), and a significant reduction in expression of the cell-cycle inhibitor p27(kip1). This pattern of signaling pathway changes was not observed in venous SMCs. No phosphorylation of PDGF-Rα was detected after venous SMC exposure to PDGF-AA, but there was enhanced phosphorylation of ERK1/2 and Akt in venous SMCs, similar to that seen in the arterial SMCs. PDGF-BB stimulation of venous SMC resulted in PDGF-Rß activation as well as transactivation of epidermal growth factor receptor (EGF-R); transactivation of EGF-R was not observed in arterial SMCs. These results may provide an explanation for the differential susceptibility to proliferative vascular diseases of arteries and veins.

The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways.

Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is a key oncogenic event in the pathogenesis of most anaplastic large cell lymphomas (ALCLs). The proteomic network alterations produced by this aberration remain largely uncharacterized. Using a mass spectrometry (MS)-driven approach to identify changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ribosome synthesis, survival, apoptosis evasion, angiogenesis, and cytoarchitectural organization. MS-based findings were confirmed using Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas. A subset of the proteins distinguished NPM/ALK-positive ALCLs from NPM/ALK-negative ALCLs and Hodgkin lymphoma. The multiple NPM/ALK-deregulated pathways identified by MS analysis also predicted novel biologic effects of NPM/ALK expression. In this regard, we showed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44ERK, and FRAP/mTOR signaling pathways. These findings reveal that the NPM/ALK alteration affects diverse cellular pathways, and provide novel insights into NPM/ALK-positive ALCL pathobiology. Our studies carry important implications for the use of MS-driven approaches for the elucidation of neoplastic pathobiology, the identification of novel diagnostic biomarkers, and pathogenetically relevant therapeutic targets.

Surveillance and identification of clusters of healthcare workers with coronavirus disease 2019 (COVID-19): Multidimensional interventions at a comprehensive cancer center.

BACKGROUND: Cases of novel coronavirus disease 2019 (COVID-19) were first reported in Wuhan, China, in December 2019. In this report, we describe 3 clusters of COVID-19 infections among healthcare workers (HCWs), not associated with patient exposure, and the interventions undertaken to halt ongoing exposure and transmission at our cancer center. METHODS: A cluster of cases was defined as 2 or more cases of severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive COVID-19 among HCWs who work in the same unit area at the same time. Cases were identified by real-time reverse transcription polymerase chain reaction testing. Contact tracing, facility observations, and infection prevention assessments were performed to investigate the 3 clusters between March 1 and April 30, 2020, with subsequent implementation of containment strategies. RESULTS: The initial cluster involved HCWs from an ancillary services unit, with contacts traced back to a gathering in a break room in which 1 employee was symptomatic, although not yet diagnosed with COVID-19, with subsequent transmission to 7 employees. The second cluster involved 4 employees and was community related. The third cluster involved only 2 employees with possible transmission while working in the same office at the same time. A step-up approach was implemented to control the spread of infection among employees, including universal masking, enhanced cleaning, increase awareness, and surveillance testing. No nosocomial transmission to patients transpired. CONCLUSIONS: To our knowledge, this is the first report of a hospital-based cluster of COVID-19 infections among HCWs in a cancer hospital describing our steps to mitigate further transmission.

A Psychometric Analysis of the Social Anxiety Scale for Adolescents Among Youth With Autism Spectrum Disorder: Caregiver-Adolescent Agreement, Factor Structure, and Validity.

Social anxiety is common among adolescents with autism spectrum disorder (ASD). An ongoing challenge for both research and clinical practice in ASD is the assessment of anxious symptomatology. Despite its widespread use in samples of youth with ASD, the Social Anxiety Scale for Adolescents (SAS-A) has not received psychometric evaluation within this population; thus, the validity of its use in research and clinical practice for ASD remains unclear. The present study conducted a psychometric analysis of caregiver and adolescent SAS-A forms in a sample of adolescents with ASD (N = 197). Results revealed (1) poor caregiver-adolescent item-level agreement, (2) a two-factor structure, (3) lack of measurement invariance between reporters, and (4) modest evidence for convergent and discriminant validity. Overall, findings suggest that this measure demonstrates reasonable psychometric properties in an ASD sample. Lack of measurement invariance, however, calls for careful interpretation of research involving the SAS-A in ASD samples, particularly when the primary goal is to compare adolescent and caregiver reports. The implications of these findings for future research and clinical practice are discussed.

Effects of exercise on hematological parameters, circulating side population cells, and cytokines.

OBJECTIVE: To determine the effects of exercise and/or training on hematologic indices, circulating side population (SP) cells, and cytokines. Specifically hemoglobin (Hgb), hematocrit (Hct), white blood cell (WBC) and platelet (Plt) numbers, SP cells and plasma vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels were analyzed before and following exercise to maximal fatigue. MATERIALS AND METHODS: Thirty-seven nonsmoking subjects, aged 19 to 35 years, free of cardiopulmonary disease were enrolled and characterized as "trained" or "untrained." Standard hematologic indices were measured. Blood cells were stained with Hoechst 33342 vital dye and analyzed using flow cytometry for enumeration of SP cells. The levels of IL-6 and VEGF were determined by enzyme-linked immunosorbent assay. RESULTS: Trained individuals had higher oxygen utilization and significantly longer exercise times than untrained individuals. Following exercise, significant increases were observed in Hgb, Hct, Plt, SP cell numbers, and IL-6 levels. These changes occurred in both trained and untrained individuals of both genders. No significant change in WBC numbers or VEGF levels was observed. Although circulating SP cell numbers were significantly increased, the "quality" of SP cells, defined by the ratio of lower SP to upper SP cells, was unchanged. Increases in SP cells did not correlate with cytokine levels. CONCLUSION: Exercise increased Hgb, Hct, and Plt numbers, circulating SP cell numbers and IL-6 levels in young, healthy individuals of both genders and all fitness levels. These changes in hematologic, hematopoietic, and cytokine parameters, suggest that exercise can have a physiologic impact by potentially mobilizing stem cells and thereby enhancing tissue repair mechanisms.

Promoting child and adolescent mental health in the context of the HIV/AIDS pandemic with a focus on sub-Saharan Africa.

BACKGROUND: The pandemic of HIV/AIDS is actually a composite of many regional and national-level epidemics. The progress made in many parts of the developed and developing world is tempered by the continued devastating consequences of HIV infection in sub-Saharan Africa (SSA). This review focuses on the ways in which children and adolescents are impacted by the epidemic, giving particular attention to their mental health. METHODS: A health promotion framework is adopted to guide analysis. Three issues are covered: prevention of HIV infection, care and treatment of children infected with HIV, and care of children whose caregivers are ill or have died of AIDS. Existing reviews and literature search engines were used to review the scientific literature, focusing on the past five years. RESULTS: Preventive interventions continue to manifest limited benefits in behavioral changes. More complex causal models and improved behavioral measures are needed. In the African context, the time has come to view pediatric AIDS as a chronic disease in which the mental health of caregivers and children influences important aspects of disease prevention and management. Increasingly sophisticated studies support earlier findings that social and psychological functioning, educational achievement and economic well-being of children who lose parents to AIDS are worse than that of other children. CONCLUSIONS: Important changes are taking place in SSA in increased access to HIV testing and antiretroviral therapies. To be effective in promoting mental health of children and adolescents, interventions require a more fundamental understanding of how to build HIV competence at personal and community levels. A key recommendation calls for the design and execution of population-based studies that include both multilevel and longitudinal features. Such rigorous conceptual and empirical investigations that assess the capacities of children are required to mobilize children, families and communities in comprehensive actions plans for prevention, treatment and care in response to the enduring HIV/AIDS pandemic.

Young citizens as health agents: use of drama in promoting community efficacy for HIV/AIDS.

A community-based cluster randomized control trial in a medium-sized municipality in Tanzania was designed to increase local competence to control HIV/AIDS through actions initiated by children and adolescents aged 10 to 14 years. Representative groups from the 15 treatment communities reached mutual understanding about their objectives as health agents, prioritized their actions, and skillfully applied community drama ("skits") to impart knowledge about the social realities and the microbiology of HIV/AIDS. In independently conducted surveys of neighborhood residents, differences were found between adults who did and did not witness the skits in their beliefs about the efficacy of children as HIV/AIDS primary change agents.

Social difficulties in youth with autism with and without anxiety and ADHD symptoms.

Social difficulties inherent to autism spectrum disorder are often linked with co-occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co-occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co-occurring symptom subgroups (Anxiety, ADHD, Both, Neither)-namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Autism Research 2018, 11: 1679-1689. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested.

Physical therapist management following rotator cuff repair for a patient with postpolio syndrome.

BACKGROUND AND PURPOSE: Postpoliomyelitis sequelae, such as gait instability and progressive weakness, predispose people with postpolio syndrome to secondary disabilities. With aging, people who depend on their upper extremities to accommodate lower-extremity deficits may anticipate overuse injuries. The purpose of this case report is to describe the use of mobilization and exercise in postoperative rehabilitation of rotator cuff surgery on a patient with postpolio syndrome. CASE DESCRIPTION: A 48-year-old woman with postpolio syndrome had rotator cuff surgical repair followed by physical therapy intervention. Maitland mobilization and mild functional exercises were chosen to avoid triggering fatigue. OUTCOMES: Measurements taken preoperatively, before and after physical therapy intervention, and 2 years after intervention showed return to independent status with excellent retention. DISCUSSION: No fatigue or overuse weakness was encountered. This is the first case report to document physical therapy following rotator cuff repair in a patient with postpolio syndrome.

Are differences in leg length predictive of lateral patello-femoral pain?

BACKGROUND AND PURPOSE: Lateral patello-femoral pain can shorten an athletic career and generally decrease an individual's physical activity and functional level, such as preventing stair climbing and reducing the ability to rise from a chair. Leg length inequality is associated with patello-femoral pain. A leg length test that best distinguishes the difference between people who have lateral patello-femoral pain and those who do not would have clinical utility. The purpose of the present study was, first, to determine if unilateral, lateral patello-femoral pain was associated with the longer leg when inequality of leg lengths existed and, second, to determine if leg length direct measurement, indirect measurement or quadriceps angle (Q angle) could correctly classify participants according to the presence or absence of patello-femoral pain. METHOD: The study used an ex post facto, two-group quasi-experimental design. A volunteer sample of 52 participants (14 males, 38 females), ranged in age from 18 to 52 years. Three methods were used to measure leg lengths: palpation meter (PALM) on anterior superior iliac spines (ASIS) while participants maintained centred weight-bearing position on a high resolution pressure mat; tape measurement from ASIS to medial malleolus (supine); tape measurement from ASIS to lateral malleolus (supine). Additionally, Q angle was measured in supine position. Patellar grind test, medial retinacular and lateral patellar palpation screened for patello-femoral pain. RESULTS: Logistic regression analysis determined correctness of membership in painful and non-painful patello-femoral groups. The PALM method of indirect measurement of leg length differences overall correctly classified approximately 83 % of the participants. Tape measure to medial and lateral malleoli as well as Q angle did not yield significant results. CONCLUSION: The results suggested that the PALM method of measuring leg length differences may have clinical utility in differentiating between patients who are likely to sustain patello-femoral pain syndrome and those who will not.

Methods of pain assessment in residents of long-term care facilities: a pilot study.

OBJECTIVES: Structured programs for routine pain assessment and treatment are necessary to optimize care for residents of long-term care facilities (LTCFs). A pilot study was designed to develop, implement, and evaluate a system for pain assessment and monitoring in a LTCF. Additional goals were to determine whether a verbal and/or non-verbal tool adequately assess pain in residents of LTCFs and whether the pharmacologic therapy for pain changes with the implementation of a pain assessment and monitoring system. DESIGN: Quantitative, nonexperimental design using two pain assessment tools. SETTING: The study was conducted at a LTCF in a rural midwestern setting. PARTICIPANTS: The study population for phase I included residents on any pain medication (regularly scheduled or as needed) on the secure dementia unit. The target population for phase II consisted of residents on any pain medication on an open unit. INTERVENTION: Training was provided to the nursing staff on how to use two pain assessment tools, one verbal (colored visual analog scale) and one nonverbal (observed pain target behaviors), and documentation. In addition, a continuing education program on pain assessment and management in elderly residents and barriers to pain management in LTCFs was offered to medical providers. MEASUREMENTS: Evaluation with the colored visual analog scale (CVAS) occurred twice daily. Pain target behaviors were monitored throughout the day and recorded by nursing staff at the end of each shift. All residents in the study population were monitored daily for six months. RESULTS: Most of the residents on both units were unable to use the verbal tool; however, the nonverbal tool was used successfully for all residents studied. On the dementia unit, the use of pain medications increased, and pain target behaviors decreased during the study period; on the open unit, the use of pain medications remained stable, and pain target behaviors decreased. CONCLUSION: These data suggest that an increase in awareness of pain may facilitate an improvement in the assessment and management of pain in residents of LTCFs. The feasibility of the nonverbal pain monitoring method shown in this study has positive implications on quality of care issues if generalizable to a larger population.

Regulation of COX-2 transcription in a colon cancer cell line by Pontin52/TIP49a.

Cyclooxygenase-2 (COX-2) is expressed early in colon carcinogenesis and is known to play a crucial role in the progress of the disease. Here we show that the regulation of the expression of this enzyme in a colon cancer cell line, and in patients, is associated with overexpression of the Wnt pathway-associated proteins, Pontin52/TIP49a and LEF-1. Recently shown to be essential for transformation via the c-Myc pathway, Pontin52/TIP49a promotes COX-2 expression in tissue culture and is overexpressed in colon cancer tissue, co-localizing with COX-2 expression in transformed tissue, relative to paired normal tissue.

Enhancing adolescent self-efficacy and collective efficacy through public engagement around HIV/AIDS competence: a multilevel, cluster randomized-controlled trial.

The potential capacity of children to confront the HIV/AIDS pandemic is rarely considered. Interventions to address the impact of the pandemic on children and adolescents commonly target only their vulnerabilities. We evaluated the Young Citizens Program, an adolescent-centered health promotion curriculum designed to increase self- and collective efficacy through public education and community mobilization across a municipality in the Kilimanjaro Region of Tanzania. The theoretical framework for the program integrates aspects of human capability, communicative action, social ecology and social cognition. The design consists of a cluster randomized-controlled trial (CRCT). Fifteen pairs of matched geopolitically defined neighborhoods of roughly 2000-4000 residents were randomly allocated to treatment and control arms. Within each neighborhood cluster, 24 randomly selected adolescents, ages 9-14, deliberated on topics of social ecology, citizenship, community health and HIV/AIDS competence. Building on their acquired understanding and confidence, they dramatized the scientific basis and social context of HIV infection, testing and treatment in their communities over a 28-week period. The curriculum comprised 5 modules: Group Formation, Understanding our Community, Health and our Community, Making Assessments and Taking Action in our Community and Inter-Acting in our Community. Adolescent participants and adult residents representative of their neighborhoods were surveyed before and after the intervention; data were analyzed using multilevel modeling. In treatment neighborhoods, adolescents increased their deliberative and communicative efficacy and adults showed higher collective efficacy for children. Following the CRCT assessments, the control group received the same curriculum. In the Kilimanjaro Region, the Young Citizens Program is becoming recognized as a structural, health promotion approach through which adolescent self-efficacy and child collective efficacy are generated in the context of civil society and local government.

Engaging patients in managing their health care: patient perceptions of the effect of a total joint replacement presurgical class.

OBJECTIVE: To engage patients in managing their health care especially in relation to a total joint replacement (TJR). With the aging of the American population and the advent of new technology, there is an increase in TJRs. As the pendulum swings from evidence-based medicine to patient-centered medicine, presurgical education is preparing patients for their surgical experience. Most research studies on such education are quantitative in nature, preventing patients' voices from being heard. METHODS: Using a success case narrative design, 24 patients mainly from the Kaiser Permanente Downey Medical Center were interviewed regarding their pre- and postsurgical experiences. RESULTS: The study findings demonstrate that patient education, in the form of classes, with recognition of the participants' physical needs, social needs, concrete supports, and psychological needs as well as the willingness of the participants to work with their health care team can promote patient engagement and improved quality of life. CONCLUSION: The TJR class was found to promote a sense of social connectedness and fostered participants' independence. The results of this study can assist health care professionals to improve their practice by designing presurgical programs to meet the needs of their patients.

Correlation of three different knee joint position sense measures.

OBJECTIVE: The purpose of this study was to investigate correlation during concurrent measurement among three knee joint position sense (JPS) measures in sitting position and between two measures in standing position. METHODS: Isokinetic dynamometer, electrogoniometer, and two dimensional (2D) video analysis were used for measuring knee JPS. The JPS was measured both in sitting and standing positions. All three measures were employed concurrently to measure knee JPS in sitting position; however, only the electrogoniometer and 2D video analysis were concurrently used in the standing position. The knee JPS was recorded in sitting position at 15 degrees, 30 degrees, and 45 degrees and in standing at high, mid and low knee flexion positions. RESULTS: The results of the study suggest excellent correlation (0.94-0.98) between the electrogoniometer and 2D video analysis measures in standing position. In sitting position, good to excellent correlation (0.63-0.92) was found between the isokinetic dynamometer and electrogoniometer; however, fair to good correlation was found between 2D video analysis and either of the two measures (electrogoniometer [0.52-0.57] and isokinetic dynamometer [0.41-0.63]. CONCLUSION: Either 2D video or an electrogoniometer may be used to measure JPS in standing position; however, in sitting position 2D video should not be used if the camera is required to be placed at 10 degrees from the plane of motion.

Bronchodilator responsiveness in swine veterinarians.

OBJECTIVE: Swine veterinarians are known to be at risk for respiratory symptoms and airflow obstruction. The present study reassessed the prevalence of respiratory complaints and pulmonary function abnormalities in swine veterinarians and sought to characterize their response to bronchodilators. METHODS: A cross-sectional study was conducted during the American Association of Swine Veterinarians annual meeting. Subjects completed a respiratory symptom and workplace exposure history questionnaire and spirometry. Subjects with airflow obstruction were assessed for a post-bronchodilator response with beta2 agonist administration. RESULTS: Participants included 58 veterinarians (mean age, 45.5 years). Work-related symptoms assessed by questionnaire included rhinitis symptoms (60.3%), cough and chest tightness (55.2%), and wheezing (35.1%). Airflow obstruction was detected in 11/58 (19%) of subjects by spirometry. Only 2/9 (22.2%) met American Thoracic Society criteria for reversibility with bronchodilator administration. CONCLUSIONS: Respiratory symptoms and airway obstruction remain common findings in swine veterinarians. Airflow obstruction was not consistently reversible with beta agonists, suggesting that swine barn exposure may be a risk factor for irreversible airflow obstruction.