Relationship between neighborhood disadvantage and social function of Wisconsin 2- and 3-year-olds born at very low birth weight.

Objective: To examine whether (1) neighborhood disadvantage is associated with social function in 2- and 3-year-olds born at very low birth weight (<1500 g) and (2) the association between social function and child's health-related quality of life (HRQoL) is moderated by neighborhood disadvantage.

Design: Cross-sectional study using the Newborn Lung Project, a cohort of infants born at very low birth weight in 2003 and 2004 in Wisconsin.

Setting: Wisconsin.

Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection.

Signal transduction networks can be perturbed biochemically, genetically, and pharmacologically to unravel their functions. But at the systems level, it is not clear how such perturbations are best implemented to extract molecular mechanisms that underlie network function. Here, we combined pairwise perturbations with multiparameter phosphorylation measurements to reveal causal mechanisms within the signaling network response of cardiomyocytes to coxsackievirus B3 (CVB3) infection.

Toll-like receptor 4-mediated activation of p38 mitogen-activated protein kinase is a determinant of respiratory virus entry and tropism.

Respiratory viruses exert a heavy toll of morbidity and mortality worldwide. Despite this burden there are few specific treatments available for respiratory virus infections. Since many viruses utilize host cell enzymatic machinery such as protein kinases for replication, we determined whether pharmacological inhibition of kinases could, in principle, be used as a broad antiviral strategy for common human respiratory virus infections.

Mechanisms of antifungal drug resistance in Candida dubliniensis.

Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C.

Proteomic signatures in plasma during early acute renal allograft rejection.

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR).

The Society for Cardiovascular Pathology celebrating 25 disruptively exciting years.

It was 25 years ago when the Society for Cardiovascular Pathology was first organized. The Society has since devoted itself to the advancement of understanding about heart and blood vessel disorders, especially their diagnosis, and for the improvement of prevention, management, and treatment. In this 25 year span, the Society has accomplished many goals and met its initial commitments as an organization, dedication to education and learning, and to collegiality.

AECVP and SCVP 2009 recommendations for training in cardiovascular pathology.

Cardiovascular disease is of continuing importance as the result of a growing burden of risk factors in both developing and developed countries and the increasing number of elderly people worldwide. The recruitment and training of a new generation of Cardiovascular Pathologists is crucial to sustaining clinical excellence and to advancing our knowledge of cardiovascular disease. These pathologists will also have a key role in undergraduate and postgraduate training.

Adult congenital heart disease--challenges and opportunities for pathologists.

Adults living with congenital heart disease (CHD) are numerous, at a prevalence of about four per 1000 population. Many of these patients are now over the age of 40 years. Typically, these adult CHD patients have had or require one or more invasive interventions, and thus most of them have modified anatomy and physiology.

The effect of state early intervention eligibility policy on participation among a cohort of young CSHCN.

Objective: This purpose of this study was to describe differences in early intervention (EI) participation according to state among a cohort of young children with parent-reported developmental delays and disabilities.

Methods: Data were obtained from the 2005-2006 National Survey of Children With Special Health Care Needs to describe state differences in EI participation. Multilevel modeling was used to estimate the relative contributions of child sociodemographic and developmental characteristics, and state EI eligibility policy on EI participation.

Perforin-independent extracellular granzyme B activity contributes to abdominal aortic aneurysm.

Granzyme B (GZMB) is a serine protease that is abundantly expressed in advanced human atherosclerotic lesions and may contribute to plaque instability. Perforin is a pore-forming protein that facilitates GZMB internalization and the induction of apoptosis. Recently a perforin-independent, extracellular role for GZMB has been proposed.

Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection.

Our previous study reported that mouse BNIP-21 (mBNIP-21) induces apoptosis through a mitochondria-dependent pathway. To map the functional domains of mBNIP-21, we performed mutational analyses and demonstrated that the BNIP-2 and Cdc42GAP homology (BCH) domain is required for apoptosis induction by mBNIP-21 targeting the mitochondria and inducing cytochrome c release. This pro-apoptotic activity was enhanced by coxsackievirus infection.

Functional genomic analysis of peripheral blood during early acute renal allograft rejection.

Background: Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long-term graft survival. Peripheral blood biomarkers that provide evidence of early graft rejection may offer an important option for posttransplant monitoring, optimize the utility of graft biopsy, and permit timely and effective therapeutic intervention to minimize the graft damage.

Methods: In this feasibility study (n=58), we have used gene expression profiling in a case-control design to compare whole blood samples between normal subjects (n=20) and patients with (n=11) or without (n=22) biopsy-confirmed acute rejection (BCAR) or borderline changes (n=5).

Evolutionary concepts in biobanking - the BC BioLibrary.

Background: Medical research to improve health care faces a major problem in the relatively limited availability of adequately annotated and collected biospecimens. This limitation is creating a growing gap between the pace of scientific advances and successful exploitation of this knowledge. Biobanks are an important conduit for transfer of biospecimens (tissues, blood, body fluids) and related health data to research.

Genetic differences between avian and human isolates of Candida dubliniensis.

When Candida dubliniensis isolates obtained from seabird excrement and from humans in Ireland were compared by using multilocus sequence typing, 13 of 14 avian isolates were genetically distinct from human isolates. The remaining avian isolate was indistinguishable from a human isolate, suggesting that transmission may occur between humans and birds.

Vascular endothelial growth factor increases human cardiac microvascular endothelial cell permeability to low-density lipoproteins.

Background: Endothelial cell hyperpermeability is a proposed mechanism of increased lipid insudation into the vessel walls of allografts. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability and its expression is upregulated in human heart allografts. The goal of these experiments was to investigate the effects of VEGF on low-density lipoprotein (LDL) permeability through confluent monolayers of human cardiac microvascular endothelial cells (HCMEC) in vitro.

Whole blood genomic biomarkers of acute cardiac allograft rejection.

Background: Significant progress has been made in cardiac transplantation over the past 30 years; however, the means for detection of acute cardiac allograft rejection remains in need of improvement. At present, the endomyocardial biopsy, an invasive and inconvenient procedure for patients, is required for the surveillance and diagnosis of acute cardiac allograft rejection. In the Biomarkers in Transplantation initiative, we investigated gene expression profiles in peripheral blood of cardiac transplant subjects as potential biomarkers for diagnosis of allograft rejection.

A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis.

The population structure of the opportunistic yeast pathogen Candida dubliniensis is composed of three main multilocus sequence typing clades (clades C1 to C3), and clade C3 predominantly consists of isolates from the Middle East that exhibit high-level resistance (MIC(50) > or = 128 microg/ml) to the fungicidal agent flucytosine (5FC). The close relative of C. dubliniensis, C.

Collagen matrix remodeling in 3-dimensional cellular space resolved using second harmonic generation and multiphoton excitation fluorescence.

The structural remodeling of collagen is important in biological processes such as fibrosis, developmental morphogenesis and wound repair. Highly ordered collagen macromolecules produce second harmonic generation signals without the need for any exogenous label. Conversely, the cellular components stained with exogenous labels generate multiphoton excitation fluorescence signals.

Urinary tract infections in 1- to 3-month-old infants: ambulatory treatment with intravenous antibiotics.

Objective: The goal was to examine the feasibility of outpatient management for 1- to 3-month-old infants with febrile urinary tract infections.

Methods: A cohort study was performed with all children 30 to 90 days of age who were evaluated for presumed febrile urinary tract infections in the emergency department of a tertiary-care pediatric hospital between January 1, 2005, and September 30, 2007. Patients were treated with intravenously administered antibiotics as outpatients in a day treatment center unless they met exclusion criteria, in which case they were hospitalized.

Searching for 'omic' biomarkers.

Cardiovascular diseases impose enormous social and economic burdens on both individual citizens and on society as a whole. Clinical indicators such as high blood pressure, blood cholesterol and obesity have had some utility in identifying those who are at increased risk of cardiovascular events. However, there remains an urgent need for sensitive and specific indicators, preferably acquired through minimally invasive means, to help stratify patients for more personalized health care.

ATP-binding cassette transporter A1 expression and apolipoprotein A-I binding are impaired in intima-type arterial smooth muscle cells.

Background: Accumulation of excess cholesterol by intimal arterial smooth muscle cells (SMCs) contributes to the formation of foam cells in atherosclerotic lesions. The purpose of this study was to examine the expression and activity of ATP-binding cassette transporter A1 (ABCA1) in model intimal and medial arterial SMCs, in human atherosclerotic coronary artery intimal and medial layers, and in human intimal and medial SMCs.

Methods And Results: Model intimal arterial SMCs showed increased cholesteryl ester accumulation, absence of apolipoprotein A-I-mediated lipid efflux, markedly diminished ABCA1 expression, and poor apoA-I binding compared with medial-layer SMCs.

Matrix metalloproteinases in the pathogenesis of viral heart disease.

Matrix metalloproteinases (MMPs) are enzymes that digest the extracellular matrix and regulate the immune response by cleavage of chemokines and cytokines into products with altered activities. Matrix metalloproteinase expression in viral heart disease has been linked to the onset of myocarditis and the long-term sequelae associated with this illness. However, MMPs are also expressed as a functional part of the immune response, and it was recently shown that MMP-9 is a beneficial part of the antiviral immune response in viral myocarditis.

ERK MAP kinase-activated Arf6 trafficking directs coxsackievirus type B3 into an unproductive compartment during virus host-cell entry.

Clathrin- and caveolae-mediated endocytosis have been implicated in the productive entry of many viruses into host cells. ADP-ribosylation factor 6 (Arf6)-dependent endocytosis is another endocytosis pathway that traffics from the cell surface and it is the only Arf that traffics at the plasma membrane. However, little is known about Arf6-dependent trafficking during virus entry.