Towards Improving Transparency of Count Data Regression Models for Health Impacts of Air Pollution

In studies on the health impacts of air pollution, regression analysis continues to advance far beyond classical linear regression, which many scientists may have become familiar with in an introductory statistics course. With each new level of complexity, regression analysis may become less transparent, even to the analyst working with the data. This may be especially true in count data regression models, where the response variable (typically given the symbol y) is count data (i.e., takes on values of 0, 1, 2, …). In such models, the normal distribution (the familiar bell-shaped curve) for the residuals (i.e., the differences between the observed values and the values predicted by the regression model) no longer applies. Unless care is taken to correctly specify just how those residuals are distributed, the tendency to accept untrue hypotheses may be greatly increased. The aim of this paper is to present a simple histogram of predicted and observed count values (POCH), which, while rarely found in the environmental literature but presented in authoritative statistical texts, can dramatically reduce the risk of accepting untrue hypotheses. POCH can also increase the transparency of count data regression models to analysts themselves and to the scientific community in general

H&E staining of biceps tendons—Group-1 (Patient numbers—PT3, PT6, PT8 and PT10) and Group-2 (Patient numbers–PT2, PT4, PT13 and PT9).

<p>The green arrows show tendon cells; black arrows point inflammation; red arrows indicate angiogenesis; blue arrows show ECM disorganization; violet arrows point fatty infiltration; and yellow arrows indicate normal ECM with dense collagen deposition. The inflammation and fatty infiltration were not evident in Group-2 while ECM disorganization was less prominent compared to Group-1. The figures are shown in 400x magnification.</p

MicroRNAs Associated with Shoulder Tendon Matrisome Disorganization in Glenohumeral Arthritis

<div><p>The extracellular matrix (ECM) provides core support which is essential for the cell and tissue architectural development. The role of ECM in many pathological conditions has been well established and ECM-related abnormalities leading to serious consequences have been identified. Though much has been explored in regards to the role of ECM in soft tissue associated pathologies, very little is known about its role in inflammatory disorders in tendon. In this study, we performed microRNA (miRNA) expression analysis in the long head of the human shoulder biceps tendon to identify key genes whose expression was altered during inflammation in patients with glenohumeral arthritis. We identified differential regulation of matrix metalloproteinases (MMPs) that could be critical in collagen type replacement during tendinopathy. The miRNA profiling showed consistent results between the groups and revealed significant changes in the expression of seven different miRNAs in the inflamed tendons. Interestingly, all of these seven miRNAs were previously reported to have either a direct or indirect role in regulating the ECM organization in other pathological disorders. In addition, these miRNAs were also found to alter the expression levels of MMPs, which are the key matrix degrading enzymes associated with ECM-related abnormalities and pathologies. To our knowledge, this is the first report which identifies specific miRNAs associated with inflammation and the matrix reorganization in the tendons. Furthermore, the findings also support the potential role of these miRNAs in altering the collagen type ratio in the tendons during inflammation which is accompanied with differential expression of MMPs.</p></div

Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine

Atherosclerosis is a chronic inflammatory disease and hypercholesterolemia is a risk factor. This study aims to compare the potency of lipopolysaccharide (LPS) and oxidized low-density lipoproteins (oxLDL) to induce plaque formation and increase plaque vulnerability in the carotid artery of hypercholesterolemic Yucatan microswine. Atherosclerotic lesions at the common carotid artery junction and ascending pharyngeal artery were induced in hypercholesterolemic Yucatan microswine at 5-6 months of age with balloon angioplasty. LPS or oxLDL were administered intraluminally at the site of injury after occluding the arterial flow temporarily. Pre-intervention ultrasound (US), angiography, and optical coherence tomography (OCT) were done at baseline and just before euthanasia to assess post-op parameters. The images from the US, OCT, and angiography in the LPS and the oxLDL-treated group showed increased plaque formation with features suggestive of unstable plaque, including necrotic core, thin fibrous caps, and a signal poor region more with oxLDL compared to LPS. Histomorphology of the carotid artery tissue near the injury corroborated the presence of severe lesions in both LPS and oxLDL-treated pigs but more in the oxLDL group. Vascular smooth muscle and endothelial cells treated with LPS and oxLDL showed increased folds changes in mRNA transcripts of the biomarkers of inflammation and plaque vulnerability compared to untreated cells. Collectively, the results suggest that angioplasty-mediated intimal injury of the carotid arteries in atherosclerotic swine with local administration of LPS or ox-LDL induces vulnerable plaques compared to angioplasty alone and oxLDL is relatively more potent than LPS in inducing vulnerable plaque