27 research outputs found

    Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation

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    IntroductionCanine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease. MethodsWe examined peripheral blood of diagnosed CDM dog patients comparing it to healthy control (HC) dogs. Dogs were recruited to a study at the Colorado State University Veterinary Teaching Hospital and blood samples collected for blood chemistry panels, complete blood counts (CBC), and immunologic analysis. Markers of disease progression such as glycated albumin (fructosamine, the canine equivalent of human HbA1c) and c-peptide were addressed. ResultsSignificant differences in adaptive immune lymphocytes, innate immune macrophages/monocytes and neutrophils and differences in platelets were detected between CDM and HC based on CBC. Significant differences in serum glucose, cholesterol and the liver function enzyme alkaline phosphatase were also detected. A systemic immune inflammation index (SII) and chronic inflammation index (CII) as measures of dynamic changes in adaptive and innate cells between inflammatory and non-inflammatory conditions were created with highly significant differences between CDM and HC. Th40 cells (CD4+CD40+ T cells) that are demonstrably pathogenic in mouse T1DM and able to differentiate diabetic from non-diabetic subjects in human T1DM were significantly expanded in peripheral blood mononuclear cells.ConclusionsBased on each clinical finding, CDM can be categorized as an autoimmune condition. The association of significantly elevated Th40 cells in CDM when compared to HC or to osteoarthritis, a chronic but non-autoimmune disease, suggests peripheral blood Th40 cell numbers as a biomarker that reflects CDM chronic inflammation. The differences in SII and CII further underscore those findings

    Accurate neonatal heart rate monitoring using a new wireless, cap mounted device

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    © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica Aim: A device for newborn heart rate (HR) monitoring at birth that is compatible with delayed cord clamping and minimises hypothermia risk could have advantages over current approaches. We evaluated a wireless, cap mounted device (fhPPG) for monitoring neonatal HR. Methods: A total of 52 infants on the neonatal intensive care unit (NICU) and immediately following birth by elective caesarean section (ECS) were recruited. HR was monitored by electrocardiogram (ECG), pulse oximetry (PO) and the fhPPG device. Success rate, accuracy and time to output HR were compared with ECG as the gold standard. Standardised simulated data assessed the fhPPG algorithm accuracy. Results: Compared to ECG HR, the median bias (and 95% limits of agreement) for the NICU was fhPPG −0.6 (−5.6, 4.9) vs PO −0.3 (−6.3, 6.2) bpm, and ECS phase fhPPG −0.5 (−8.7, 7.7) vs PO −0.1 (−7.6, 7.1) bpm. In both settings, fhPPG and PO correlated with paired ECG HRs (both R2=0.89). The fhPPG HR algorithm during simulations demonstrated a near-linear correlation (n=1266, R2=0.99). Conclusion: Monitoring infants in the NICU and following ECS using a wireless, cap mounted device provides accurate HR measurements. This alternative approach could confer advantages compared with current methods of HR assessment and warrants further evaluation at birth

    Reflections on Seminole Rock: The Past, Present, and Future of Deference to Agency Regulatory Interpretations

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    Seminole Rock (or Auer) deference has captured the attention of scholars, policymakers, and the judiciary. That is why Notice & Comment, the blog of the Yale Journal on Regulation and the American Bar Association’s Section of Administrative Law & Regulatory Practice, hosted an online symposium from September 12 to September 23, 2016 on the subject. This symposium contains over 20 contributions addressing different aspects of Seminole Rock deference. Topics include: History of Seminole Rock Empirical Examinations of Seminole Rock Understanding Seminole Rock Within Agencies Understanding Seminole Rock as Applied to Tax, Environmental Law, and Criminal Sentencing Why Seminole Rock Matters Should the Supreme Court Overrule Seminole Rock? Would Overruling Seminole Rock Have Unintended Consequences? What Might the Supreme Court Do? What Might Congress Do? The Future of Seminole Roc

    Children must be protected from the tobacco industry's marketing tactics.

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    Chemokine Scavenger D6 Is Expressed by Trophoblasts and Aids the Survival of Mouse Embryos Transferred into Allogeneic Recipients

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    Proinflammatory CC chemokines are thought to drive recruitment of maternal leukocytes into gestational tissues and regulate extravillous trophoblast migration. The atypical chemokine receptor D6 binds many of these chemokines and is highly expressed by the human placenta. D6 is thought to act as a chemokine scavenger because, when ectopically expressed in cell lines in vitro, it efficiently internalizes proinflammatory CC chemokines and targets them for destruction in the absence of detectable chemokine-induced signaling. Moreover, D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient fetuses in D6-deficient female mice show increased susceptibility to inflammation-driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with specific intracellular distribution patterns, in trophoblast-derived cells in human placenta, decidua, and gestational membranes throughout pregnancy and in trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for the first time, that endogenous D6 in a human choriocarcinoma-derived cell line can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can specifically associate with human syncytiotrophoblasts in term placenta in situ. Moreover, despite strong chemokine production by gestational tissues, levels of D6-binding chemokines in maternal plasma decrease during pregnancy, even in women with pre-eclampsia, a disease associated with increased maternal inflammation. In mice, D6 is not required for syngeneic or semiallogeneic fetal survival in unchallenged mice, but interestingly, it does suppress fetal resorption after embryo transfer into fully allogeneic recipients. These data support the view that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface and that, in some circumstances, this can help to ensure fetal survival. The Journal of Immunology, 2010,184: 3202-321
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