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  • 1
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    Online Resource
    Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo
    SAGE Publications ; 2009
    In:  Innate Immunity Vol. 15, No. 2 ( 2009-04), p. 109-120
    Details
    In: Innate Immunity, SAGE Publications, Vol. 15, No. 2 ( 2009-04), p. 109-120
    Abstract: Microbial components such as lipopolysaccharide (LPS) bind to Toll-like receptors (TLRs) and activate innate and inflammatory responses. Responses to LPS and other microbial components are limited by the activation of negative feedback mechanisms that reduce responsiveness to subsequent LPS exposure, often termed LPS tolerance. Our laboratory has previously shown that calcineurin, a phosphatase known for its activation of T cells via NFAT, negatively regulates the TLR pathway in macrophages; consequently, calcineurin inhibitors (FK506 and cyclosporin A) mimic TLR ligands in activating the TLR pathway, NF-KB, and associated innate and inflammatory responses. This study investigated the physiological consequences of calcineurin inactivation for LPS-induced inflammatory responses in vitro and in vivo using two models: calcineurin inhibition by FK506 (tacrolimus) and myeloid cell-specific calcineurin deletion. Activation of dendritic cells and macrophages with FK506 in vitro was shown to induce a state of reduced responsiveness to LPS (i.e. a form of LPS tolerance). Similarly, macrophages from FK506-treated mice or from mice in which the calcineurin B1 (CnB1) subunit was conditionally knocked out in myeloid cells were found to have diminished LPS-induced inflammatory responses. In addition, mice with CnB1-deficient myeloid cells and mice undergoing FK506 treatment showed improved survival and recovery when challenged with high doses of systemic LPS compared to controls. These results demonstrate that inactivation of calcineurin in macrophages and other myeloid cells by inhibition or deletion can induce a form of LPS tolerance and protect the host from LPS toxicity in vivo.
    Type of Medium: Online Resource
    ISSN: 1753-4259 , 1753-4267
    URL: Article
    DOI: 10.1177/1753425908100928
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2381250-3
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  • 2
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    Racial/Ethnic Differences in Child Protective Services Reporting, Substantiation and Placement, With Comparison to Non-CPS Risks and Outcomes: 2005–2019
    SAGE Publications ; 2023
    In:  Child Maltreatment Vol. 28, No. 4 ( 2023-11), p. 683-699
    Details
    In: Child Maltreatment, SAGE Publications, Vol. 28, No. 4 ( 2023-11), p. 683-699
    Abstract: We used National Child Abuse and Neglect Data System and Census data to examine Black–White and Hispanic–White disparities in reporting, substantiation, and out-of-home placement both descriptively from 2005–2019 and in multivariate models from 2007–2017. We also tracked contemporaneous social risk (e.g., child poverty) and child harm (e.g., infant mortality) disparities using non-child protective services (CPS) sources and compared them to CPS reporting rate disparities. Black–White CPS reporting disparities were lower than found in non-CPS risk and harm benchmarks. Consistent with the Hispanic paradox, Hispanic–White CPS reporting disparities were lower than risk disparities but similar to harm disparities. Descriptive and multivariate analyses of data from the past several years indicated that Black children were less likely to be substantiated or placed into out-of-home care following a report than White children. Hispanic children were slightly more likely to be substantiated or placed in out-of-home care than White children overall, but this difference disappeared in multivariate models. Available data provide no evidence that Black children were overreported relative to observed risks and harms reflected in non-CPS data. Reducing reporting rates among Black children will require addressing broader conditions associated with maltreatment.
    Type of Medium: Online Resource
    ISSN: 1077-5595 , 1552-6119
    URL: Article
    DOI: 10.1177/10775595231167320
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2018206-5
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  • 3
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    Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: The Breastfeeding, Antiretrovirals and Nutrition study experience
    SAGE Publications ; 2015
    In:  Clinical Trials Vol. 12, No. 2 ( 2015-04), p. 156-165
    Details
    In: Clinical Trials, SAGE Publications, Vol. 12, No. 2 ( 2015-04), p. 156-165
    Abstract: Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource-limited settings, where high lost to follow-up rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. Methods The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. Results During the study, intensive tracing efforts were initiated after the first 1686 mother–infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study’s end, 290 (12.2%) of the 2369 mother–infant pairs were lost to follow-up. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of lost to follow-up. Conclusion In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study’s provision of nutritional support, including a family maize supplement, which may have contributed to patient retention.
    Type of Medium: Online Resource
    ISSN: 1740-7745 , 1740-7753
    URL: Article
    DOI: 10.1177/1740774514562031
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2159773-X
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  • 4
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    Efficacy and Safety of LY3127804, an Anti-Angiopoietin-2 Antibody, in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Patients Hospitalized with Pneumonia and Presumed or Confirmed COVID-19
    SAGE Publications ; 2022
    In:  Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine Vol. 16 ( 2022-01), p. 117954842211193-
    Details
    In: Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, SAGE Publications, Vol. 16 ( 2022-01), p. 117954842211193-
    Abstract: Severe cases of coronavirus disease 2019 (COVID-19) are characterized by progressive respiratory failure and the development of acute respiratory distress syndrome (ARDS), with high mortality rates for patients requiring mechanical ventilation. Levels of the vascular growth factor Angiopoietin 2 (Ang2) in plasma have been strongly correlated with increased ARDS risk in patients with pneumonia or sepsis. The intent of this study was to determine whether LY3127804, an anti-Ang2 monoclonal antibody, could reduce the need for mechanical ventilation among patients admitted to the hospital with pneumonia and presumed or confirmed COVID-19. METHODS Patients admitted to hospital with confirmed pneumonia, presumed or confirmed COVID-19, and infiltrates on chest imaging and/or oxygen saturation of ≤ 95% on room air were stratified by age group ( 〈 65 years and ≥ 65 years), sex, and site and randomly assigned 1:1 within each stratum to receive either LY3127804 (20 mg/kg) or placebo on Day 1 and possibly on Day 15. The primary end point for this study was number of days in which a patient did not require a ventilator over the 28-day study period. RESULTS Interim analysis assessed study futility after 95 randomized patients had 28-day data available and showed no benefit of LY3127804 in reducing the number of ventilator days over placebo. The study was subsequently terminated. CONCLUSION LY3127804 treatment did not decrease the need for ventilator usage in patients hospitalized with pneumonia and presumed or confirmed COVID-19. ClinicalTrials.gov identifier NCT04342897
    Type of Medium: Online Resource
    ISSN: 1179-5484 , 1179-5484
    URL: Article
    DOI: 10.1177/11795484221119316
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2583465-4
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  • 5
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    Phenotypic and Aetiological Associations Between Psychopathic Tendencies, Autistic Traits, and Emotion Attribution
    SAGE Publications ; 2009
    In:  Criminal Justice and Behavior Vol. 36, No. 11 ( 2009-11), p. 1198-1212
    Details
    In: Criminal Justice and Behavior, SAGE Publications, Vol. 36, No. 11 ( 2009-11), p. 1198-1212
    Abstract: Some behavioural overlap exists between psychopathic tendencies and autistic traits, and both phenotypes are thought to be associated with problems in empathy. However, the broad behavioural profiles and the cognitive-affective deficits associated with the two conditions are at least partly separable. The main aim of this study was to assess the extent to which the aetiology of psychopathic tendencies is independent of autistic traits. A secondary aim was to study the aetiology of emotion attribution ability and its association with psychopathic tendencies and autistic traits. Based on data from a sample of 642 twin pairs, the genetic and nonshared environmental influences related to psychopathic tendencies were largely unique to each phenotype. Common environmental influences between psychopathic tendencies and autistic traits overlapped. Poorer emotion attribution ability was associated with increased psychopathic tendencies and autistic traits, and these associations were mainly explained by common genetic factors.
    Type of Medium: Online Resource
    ISSN: 0093-8548 , 1552-3594
    URL: Article
    DOI: 10.1177/0093854809342949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 1500128-3
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  • 6
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    Interleukin-6 Levels Decrease in Effluent from Patients Dialyzed with Bicarbonate/Lactate–Based Peritoneal Dialysis Solutions
    SAGE Publications ; 2001
    In:  Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis Vol. 21, No. 3_suppl ( 2001-12), p. 102-107
    Details
    In: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, SAGE Publications, Vol. 21, No. 3_suppl ( 2001-12), p. 102-107
    Abstract: Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs). These characteristics, along with inflammation, are believed to contribute to membrane dysfunction in peritoneal dialysis patients. A new PD solution containing a bicarbonate/ lactate buffer system with physiologic pH and low GDPs has shown improved biocompatibility in both in vitro and ex vivo studies. In the present study, the concentrations of cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and vascular endothelial growth factor (VEGF), were measured in timed overnight effluents from PD patients continuously dialyzed with either lactate-based control solution (C) or bicarbonate/lactate–based solution (B/L) for 6 months. ♦ Methods Effluents from 92 continuous ambulatory peritoneal dialysis (CAPD) patients were collected when the patients were entered into the study (baseline, all patients on C for more than 3 months), and at 3 and 6 months following randomization to C ( n = 31) or to B/L ( n = 61). Effluent samples were filtered, stored frozen, and then assayed for IL-6, TNFα, and VEGF by ELISA. ♦ Results A significant decrease in effluent IL-6 was seen at 3 months and at 6 months in the B/L-treated patients. Levels of VEGF were significantly reduced at 3 months. No changes in the levels of IL-6 or VEGF were seen in the C-treated patients, and no changes in TNFα were seen in either group over time. ♦ Conclusions Treatment with B/L is associated with decreased IL-6 synthesis and decreased VEGF secretion. The data suggest that the use of B/L solution is associated with reduced intraperitoneal inflammation and potential for angiogenesis. The use of B/L solution may, over time, help to restore peritoneal homeostasis and therefore preserve the function of the membrane in peritoneal dialysis.
    Type of Medium: Online Resource
    ISSN: 0896-8608 , 1718-4304
    URL: Article
    DOI: 10.1177/089686080102103S17
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2001
    detail.hit.zdb_id: 2075957-5
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  • 7
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    Erratum
    SAGE Publications ; 2022
    In:  Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine Vol. 16 ( 2022-01), p. 117954842211275-
    Details
    In: Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, SAGE Publications, Vol. 16 ( 2022-01), p. 117954842211275-
    Type of Medium: Online Resource
    ISSN: 1179-5484 , 1179-5484
    URL: Article
    DOI: 10.1177/11795484221127555
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 8
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    Application of a Polymerase Chain Reaction Assay for Detection of Proliferative Enteritis-Affected Swine Herds
    SAGE Publications ; 1996
    In:  Journal of Veterinary Diagnostic Investigation Vol. 8, No. 2 ( 1996-04), p. 181-185
    Details
    In: Journal of Veterinary Diagnostic Investigation, SAGE Publications, Vol. 8, No. 2 ( 1996-04), p. 181-185
    Abstract: A polymerase chain reaction (PCR) assay was used to confirm the presence of ileal symbiont (IS) intracellularis in 3 swine herds with a history of proliferative enteritis (PE). Two pooled fecal specimens, each comprising 5 individual stool samples, were collected from pen floors to screen for the presence of IS intracellularis and determine the age range of pigs shedding the organism. IS intracellularis was detected in the feces of clinically normal 10–25week-old grower/finisher pigs, indicating that this age range of pigs was the main source of infection for younger nursery pigs. Shedding continued without clinical disease when 10–100 g/ton of tylosin or 10 g/ton of chlortetracycline was added to the feed. PCR testing of pooled fecal samples can be used to identify groups of pigs affected with PE. The results of this study indicate that this PCR assay has the potential to accurately assess the IS intracellularis infection status of swine herds and the association of IS intracellular-is with PE and growth performance.
    Type of Medium: Online Resource
    ISSN: 1040-6387 , 1943-4936
    URL: Article
    DOI: 10.1177/104063879600800207
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1996
    detail.hit.zdb_id: 2265211-5
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  • 9
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    Detection of Pre-Invasive Lung Cancer: Technical Aspects of the LIFE Project
    SAGE Publications ; 2007
    In:  Toxicologic Pathology Vol. 35, No. 1 ( 2007-01), p. 65-74
    Details
    In: Toxicologic Pathology, SAGE Publications, Vol. 35, No. 1 ( 2007-01), p. 65-74
    Abstract: Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The LIFE (Light Induced Fluorescence Endoscopy) Project was initiated at the University of North Carolina Medical Center in November, 1999, for the dual purposes of (1) detecting pre-invasive lung cancer in high-risk patients and (2) studying the molecular biology of pre-invasive lesions of the bronchus for possible development of molecular biomarkers. Of the 47 patients enrolled, all were current or former tobacco smokers, except for 1. Fluorescence endoscopy was utilized, in addition to white light bronchoscopy, to increase the detection of intraepithelial lesions. Adjacent biopsies were submitted for permanent and frozen sections, respectively, from four predetermined sites as well as from any abnormal areas. The snap-frozen specimens were cryostat sectioned, and the mucosal epithelial cells laser capture microdissected for DNA analysis. The great majority of specimens yielded sufficiently abundant and intact DNA to accomplish the molecular objectives. Histologic concordance of adjacent permanent and frozen sections was equivalent to the concordance of adjacent permanent sections, suggesting that frozen section diagnosis was adequate for the research purpose of correlating histology with molecular analysis.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    URL: Article
    DOI: 10.1080/01926230601052659
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2007
    detail.hit.zdb_id: 2056753-4
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  • 10
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    Congenital portosystemic shunts and hepatic encephalopathy in goat kids in California : 11 cases (1999–2012)
    SAGE Publications ; 2014
    In:  Journal of Veterinary Diagnostic Investigation Vol. 26, No. 1 ( 2014-01), p. 173-177
    Details
    In: Journal of Veterinary Diagnostic Investigation, SAGE Publications, Vol. 26, No. 1 ( 2014-01), p. 173-177
    Abstract: Between 1999 and 2012, 11 cases of congenital portosystemic shunts (cPSS) resulting in hepatic encephalopathy were diagnosed in goat kids necropsied at the California Animal Health and Food Safety Laboratory System and at the Department of Pathology, Immunology & Microbiology, School of Veterinary Medicine, University of California–Davis. Affected animals included 6 females and 5 males of various breeds including Boer (5/11), Nigerian Dwarf (1/11), Saanen (1/11), Toggenburg (1/11), and mixed-breed (3/11) aged between 1.5 months and 11 months, submitted live (2/11) or dead (9/11) for necropsy. The most frequent clinical signs in these goats were ataxia, blindness, tremors, head bobbing, head pressing, seizures, circling, weakness, and ill thrift. Bile acids were measured in 2 animals, and were elevated in both cases (134 and 209 µmol/l, reference interval = 0–50 µmol/l). Necropsy findings were poor to fair body condition. Grossly, the livers of 4 animals were subjectively small. Microscopic lesions included portal spaces with increased numbers of arteriolar profiles and hypoplastic or absent portal veins, diffuse atrophy of the hepatic parenchyma with the presence of small hepatocytes and, in some cases, multifocal hepatocellular macrovesicular vacuolation. In the brain and spinal cord of all animals, there was bilateral and symmetric spongy degeneration affecting the cerebrum, mesencephalon, cerebellum, brainstem, and cervical spinal cord. In all cases, the brain lesions were consistent with hepatic encephalopathy. Congenital portosystemic shunts should be considered in the differential diagnosis of young goats with a history of ill thrift, and nonspecific neurological signs.
    Type of Medium: Online Resource
    ISSN: 1040-6387 , 1943-4936
    URL: Article
    DOI: 10.1177/1040638713518050
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2265211-5
    SSG: 22
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