Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche.

Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood.

Factors associated with SARS-CoV-2 test positivity in long-term care homes: A population-based cohort analysis using machine learning.

Background: SARS-Cov-2 infection rates are high among residents of long-term care (LTC) homes. We used machine learning to identify resident and community characteristics predictive of SARS-Cov-2 infection.

Methods: We linked 26 population-based health and administrative databases to identify the population of all LTC residents tested for SARS-Cov-2 infection in Ontario, Canada.

Predictors of mortality among long-term care residents with SARS-CoV-2 infection.

Background: While individuals living in long-term care (LTC) homes have experienced adverse outcomes of SARS-CoV-2 infection, few studies have examined a broad range of predictors of 30-day mortality in this population.

Methods: We studied residents living in LTC homes in Ontario, Canada, who underwent PCR testing for SARS-CoV-2 infection from January 1 to August 31, 2020, and examined predictors of all-cause death within 30 days after a positive test for SARS-CoV-2. We examined a broad range of risk factor categories including demographics, comorbidities, functional status, laboratory tests, and characteristics of the LTC facility and surrounding community were examined.

Long-term mortality risk stratification of liver transplant recipients: real-time application of deep learning algorithms on longitudinal data.

Background: Survival of liver transplant recipients beyond 1 year since transplantation is compromised by an increased risk of cancer, cardiovascular events, infection, and graft failure. Few clinical tools are available to identify patients at risk of these complications, which would flag them for screening tests and potentially life-saving interventions. In this retrospective analysis, we aimed to assess the ability of deep learning algorithms of longitudinal data from two prospective cohorts to predict complications resulting in death after liver transplantation over multiple timeframes, compared with logistic regression models.

c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells.

Mechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow.

Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth.

CXCL14 deficiency does not impact the outcome of influenza or Escherichia coli infections in mice.

Introduction: Chemokines are small proteins that regulate different cellular functions, such as leukocyte activation, chemoattraction and inflammation. The chemokine CXCL14 (BRAK) is a highly conserved gene among species and through evolution. It has been shown that CXCL14 is locally upregulated during viral infections, also, it has been found that this chemokine possesses direct antibacterial activities.

Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection.

The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX(-/-)) model and found that survival after infection was significantly greater in GX(-/-) mice than in GX(+/+) mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX(-/-) mice BAL fluid.

Management of acute limb ischemia in the pediatric population.

Objective: Acute limb ischemia (ALI) in pediatric patients is rare but may lead to limb loss and life-long complications. This study reviewed the experience of a Canadian tertiary pediatric center with the medical and operative management of ALI.

Methods: The medical records of inpatients diagnosed with ALI of the upper or lower limb between 1999 and 2012 were reviewed.

Innate response activator B cells aggravate atherosclerosis by stimulating T helper-1 adaptive immunity.

Background: Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other's function and shape the course of disease can illuminate our understanding of atherosclerosis.

Myocardial infarction accelerates atherosclerosis.

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis.

Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection.

Lack of microsomal prostaglandin E(2) synthase-1 in bone marrow-derived myeloid cells impairs left ventricular function and increases mortality after acute myocardial infarction.

Background: Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation.

Group V phospholipase A2 in bone marrow-derived myeloid cells and bronchial epithelial cells promotes bacterial clearance after Escherichia coli pneumonia.

Group V-secreted phospholipase A(2) (GV sPLA(2)) hydrolyzes bacterial phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role of GV sPLA(2) in the pathophysiology of Escherichia coli pneumonia. Inflammatory cells and bronchial epithelial cells both express GV sPLA(2) after pulmonary E.

Iliac branch graft in the treatment of complex aortoiliac aneurysms: early results from a North American institution.

Purpose: To describe early experience with the use of iliac branch grafts (IBGs) in aortoiliac aneurysm repair.

Materials And Methods: From July 2007 to August 2009 (25 months), 14 patients (13 men, one woman) with a mean age of 70.1 years (range, 59.

Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.

Hemorrhagic shock (HS) is associated with cardiac contractile dysfunction. Mast cell (MC) degranulation is hypothesized to mediate the cardiodepressant effect. Cardiac function was assessed after HS and resuscitation (HS/R) with the administration of the MC stabilizers to prevent MC degranulation.

Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction.

Background: Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from cyclooxygenase-2 in the inducible PGE(2) biosynthetic pathway. We caused acute MI in Ptges(+/+) and Ptges(-/-) mice to define the role of mPGES-1 in cardiac ischemic injury.

Disruption of JNK2 decreases the cytokine response to Plasmodium falciparum glycosylphosphatidylinositol in vitro and confers protection in a cerebral malaria model.

Host inflammatory responses to Plasmodium falciparum GPI (pfGPI) anchors are believed to play an important role in the pathophysiology of severe malaria. However, relatively little is known about the signal transduction pathways involved in pfGPI-stimulated inflammatory response and its potential contribution to severe malaria syndromes. In this study, we investigated the role of MAPK activation in pfGPI-induced cytokine secretion and examined the role of selected MAPKs in a model of cerebral malaria in vivo.

c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2 synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1 expression and prostaglandin E2 biosynthesis by cardiomyocytes.

Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE(2), a key proinflammatory mediator. The purpose of this study was to elucidate the regulation of mPGES-1 mRNA expression in cardiomyocytes, define the role of JNK enzymes in this process, and characterize the role of mPGES-1 in cardiomyocyte PGE(2) biosynthesis. In neonatal cardiomyocytes, interleukin-1beta and lipopolysaccharide (LPS) both stimulated mPGES-1 mRNA expression and increased mPGES-1 mRNA stability and protein synthesis but failed to increase mPGES-1 mRNA transcription.

Primary stenting of bilateral radiation-induced external iliac stenoses.

Radiation-induced arteritis is a described rare complication of radiotherapy, particularly in patients with cancer. We report bilateral radiation-induced arteritis leading to stenoses in the external iliac arteries, which was treated with primary percutaneous arterial stenting, and review the current literature on the topic.

Cytosolic phospholipase A2-alpha is necessary for platelet-activating factor biosynthesis, efficient neutrophil-mediated bacterial killing, and the innate immune response to pulmonary infection: cPLA2-alpha does not regulate neutrophil NADPH oxidase activity.

The role of a cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) in neutrophil arachidonic acid release, platelet-activating factor (PAF) biosynthesis, NADPH oxidase activation, and bacterial killing in vitro, and the innate immune response to bacterial infection in vivo was examined. cPLA(2)-alpha activity was blocked with the specific cPLA(2)-alpha inhibitor, Pyrrolidine-1 (human cells), or by cPLA(2) -alpha gene disruption (mice). cPLA(2)-alpha inhibition or gene disruption led to complete suppression of neutrophil arachidonate release and PAF biosynthesis but had no effect on neutrophil NADPH oxidase activation, FcgammaII/III or CD11b surface expression, primary or secondary granule secretion, or phagocytosis of Escherichia coli in vitro.