An audit of inpatient insulin prescriptions - how error relates to information source.

Background: The risk of hospital insulin prescription errors in the UK has remained unchanged despite the adoption of several national initiatives. This audit was conducted to evaluate whether the prescription errors were related to the information source used.

Aims: To determine what sources of information are used at the time of hospital admission of patients with diabetes to obtain details of their insulin regimen and how different sources relate to prescription errors.

Liver X receptors are required for thymic resilience and T cell output.

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)-a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity-critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire.

Sleep modulates haematopoiesis and protects against atherosclerosis.

Sleep is integral to life. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice.

Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease.

The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin β7 natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism.

Self-reactive CD4 IL-3 T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis.

Acquisition of self-reactive effector CD4 T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3-dependent amplification loop that exacerbates autoimmune inflammation.

The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes.

Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells.

ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression.

Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population.

On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity.

Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

Unlabelled: Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors.

Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages.

Background: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease.

Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis.

Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis.

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury.

IL-4 signaling drives a unique arginase+/IL-1β+ microglia phenotype and recruits macrophages to the inflammatory CNS: consequences of age-related deficits in IL-4Rα after traumatic spinal cord injury.

Alternative activation of microglia/macrophages (M2a) by interleukin (IL)-4 is purported to support intrinsic growth and repair processes after CNS injury. Nonetheless, alternative activation of microglia is poorly understood in vivo, particularly in the context of inflammation, injury, and aging. Here, we show that aged mice (18-19 months) had reduced functional recovery after spinal cord injury (SCI) associated with impaired induction of IL-4 receptor α (IL-4Rα) on microglia.

TGFβ produced by IL-10 redirected astrocytes attenuates microglial activation.

While there clearly is an intimate relationship between astrocytes and microglia, few studies have examined these potentially dynamic interactions. In this study, cytokine-mediated communication between microglia and astrocytes under inflammatory conditions was investigated. We have previously shown that activated microglia produce Interleukin (IL)-10, a regulatory cytokine that plays an important role in resolving neuroinflammation.

Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia.

Background: Traumatic brain injury (TBI) is associated with a higher incidence of depression. The majority of individuals who suffer a TBI are juveniles and young adults, and thus, the risk of a lifetime of depressive complications is a significant concern. The etiology of increased TBI-associated depression is unclear but may be inflammatory-related with increased brain sensitivity to secondary inflammatory challenges (e.

Increased micro-RNA 29b in the aged brain correlates with the reduction of insulin-like growth factor-1 and fractalkine ligand.

Microglia develop an inflammatory phenotype during normal aging. The mechanism by which this occurs is not well understood, but might be related to impairments in several key immunoregulatory systems. Here we show that micro-RNA (miR)-29a and miR-29b, 2 immunoregulatory micro-RNAs, were increased in the brain of aged BALB/c mice compared with adults.

Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory.

Impaired memory may result from synaptic glutamatergic dysregulation related to chronic neuroinflammation. GLT1 is the primary excitatory amino acid transporter responsible for regulating extracellular glutamate levels in the hippocampus. We tested the hypothesis that if impaired spatial memory results from increased extracellular glutamate due to age or experimentally induced chronic neuroinflammation in the hippocampus, then pharmacological augmentation of the glutamate transporter GLT1 will attenuate deficits in a hippocampal-dependent spatial memory task.

Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice.

Repeated social defeat (RSD) activates neuroendocrine pathways that have a significant influence on immunity and behavior. Previous studies from our lab indicate that RSD enhances the inflammatory capacity of CD11b⁺ cells in the brain and promotes anxiety-like behavior in an interleukin (IL)-1 and β-adrenergic receptor-dependent manner. The purpose of this study was to determine the degree to which mice subjected to RSD were more responsive to a secondary immune challenge.

Lipopolysaccharide-induced interleukin (IL)-4 receptor-α expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice.

In several models of aging, microglia become more inflammatory and reactive to immune challenges. For example, peripheral LPS injection causes exaggerated microglial activation associated with prolonged sickness and depressive-like behavior in aged BALB/c mice. Therefore, the purpose of this study was to determine the extent to which age-related amplified microglial activation was associated with reduced sensitivity to the anti-inflammatory and M2 promoting cytokines interleukin (IL)-10 and IL-4.

Cognitive and behavioral consequences of impaired immunoregulation in aging.

A hallmark of the aged immune system is impaired immunoregulation of the innate and adaptive immune system in the periphery and also in the central nervous system (CNS). Impaired immunoregulation may predispose older individuals to an increased frequency of peripheral infections with concomitant cognitive and behavioral complications. Thus, normal aging is hypothesized to alter the highly coordinated interactions between the immune system and the brain.

Sustained melatonin treatment blocks body mass, pelage, reproductive, and fever responses to short day lengths in female Siberian hamsters.

Winter imposes physiological challenges on individuals including increased thermoregulatory demands, risk of infection, and decreased food availability. To survive these challenges, animals living outside the tropics must appropriately distribute their energetic costs across the year, including reproduction and immune function. Individuals of many species use the annual cycle of changing day lengths (photoperiod), which is encoded by the nightly duration of melatonin secretion, to adjust physiology.

To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris).

Mammals that hibernate (hibernators) exhibit a circannual rhythm of food intake and body mass. In the laboratory during the winter hibernation period, many hibernators enter a series of multi-day torpor bouts, dropping their body temperature to near ambient, and cease to feed even if food is present in their cage. The mechanism(s) that regulates food intake in hibernators is unclear.