Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies.

Some metabolic diseases, such as diabetes and hyperlipidemia, are associated with a state of inflammation, which adversely affects cardiovascular health. Emerging evidence suggests that long-term hyperactivation of innate immune cells and their bone marrow progenitors, termed trained immunity, functions to accelerate atherosclerosis and its complications in cardiometabolic diseases. This review will focus on how trained immunity is established, particularly through metabolic and epigenetic reprogramming, to cause persistent and deleterious changes in immune cell function, even after the original stimulus has been corrected or removed.

The Effect of Non-Pharmacological and Pharmacological Interventions on Measures Associated with Sarcopenia in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible.

Primary skeletal muscle cells from chronic kidney disease patients retain hallmarks of cachexia in vitro.

Background: Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy-based animal models, translational capacity to our patient population has been challenging.

A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods.

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients (KTRs). CVD risk scores underestimate risk in this population as CVD is driven by clustering of traditional and non-traditional risk factors, which lead to prognostic pathological changes in cardiovascular structure and function. While exercise may mitigate CVD in this population, evidence is limited, and physical activity levels and patient activation towards exercise and self-management are low.

Morphometric, metabolic, and inflammatory markers across a cohort of client-owned horses and ponies on the insulin dysregulation spectrum.

In human metabolic syndrome and type II diabetes, methylglyoxal (MG), D-lactate, and several cytokines have been recognized as biomarkers of important metabolic and inflammatory processes. Equine metabolic syndrome (EMS) shares many similarities with these human counterparts. The objectives of this cross-sectional study were to compare body condition score (BCS), cresty neck score (CNS), resting insulin, MG, D-lactate, L-lactate, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) between horses with and without insulin dysregulation, as classified via combined glucose and insulin test (CGIT).

A Systematic Review of Handgrip Strength Measurement in Clinical and Epidemiological Studies of Kidney Disease: Toward a Standardized Approach.

In chronic kidney disease (CKD), handgrip strength (HGS) is recommended as a surrogate measure of protein-energy status and functional status. However, it is not routinely used because of inconsistencies such as the optimal timing of the HGS measurement and unclear guidance regarding technique. We aimed to determine the extent of variation in the protocols and methods of HGS assessment.

Characterization of the use of shock wave therapy among equine veterinarians.

Extracorporeal shock wave therapy (ESWT) research has prioritized mechanism of action and efficacy. Data regarding frequency of use and clinical opinion are not available. A web-based survey was offered to members of the American Association of Equine Practitioners; 144 responses were obtained.

Prevalence of obesity in the equine population of Saskatoon and surrounding area.

A retrospective study determined the prevalence of obesity and over-conditioning in horses in Saskatoon, Saskatchewan. Body condition score (BSC) was assessed for 290 horses from the Field Service practice at the Western College of Veterinary Medicine. The median BSC of horses was 6; however, 59 (20.

Efficacy of a single-formula acupuncture treatment for horses with palmar heel pain.

Acupuncture is used without strong scientific evidence to treat many diseases of the horse, including palmar heel pain. Research is needed to provide evidence for the application of these treatments. Within the confines of our study, acupuncture did not reliably modulate palmar heel pain in horses.

Association between HIV programs and quality of maternal health inputs and processes in Kenya.

We assessed whether quality of maternal and newborn health services is influenced by presence of HIV programs at Kenyan health facilities using data from a national facility survey. Facilities that provided services to prevent mother-to-child HIV transmission had better prenatal and postnatal care inputs, such as infrastructure and supplies, and those providing antiretroviral therapy had better quality of prenatal and postnatal care processes. HIV-related programs may have benefits for quality of care for related services in the health system.

Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model.

Posttranslational regulation of thioredoxin-interacting protein.

Thioredoxin-interacting protein (Txnip) is a metabolic regulator, which modulates insulin sensitivity and likely plays a role in type 2 diabetes. We studied the regulation of Txnip in 3T3-L1 adipocytes. Cells were incubated under different conditions and Txnip was measured by immunoblotting.

Premature lactation and retention of a mummified fetus with live birth of the co-twin in a primiparous Morgan mare.

This report describes a primiparous 8-year-old Morgan mare, which displayed premature lactation that began at approximately 240 d of gestation and lasted approximately 4 wk. The premature lactation resolved spontaneously, and the pregnancy was subsequently carried to full term with the delivery of a live foal and a mummified fetus.

First report of cyromazine resistance in a population of UK house fly (Musca domestica) associated with intensive livestock production.

Background: House fly control in livestock-rearing facilities is heavily reliant on the use of the larvicide cyromazine. While extensive use of this compound has led to the development of resistance in several countries, no elevated tolerance has so far been reported from the United Kingdom.

Results: Tolerance to cyromazine in larvae derived from a field strain collected at an intensive pig unit was significantly elevated over that of insects taken from a susceptible laboratory strain.

Mechanisms of high-glucose/insulin-mediated desensitization of acute insulin-stimulated glucose transport and Akt activation.

High-glucose/low-dose insulin-mediated insulin resistance of glucose transport was studied in 3T3-L1 adipocytes. In this model, proximal insulin signaling, including insulin receptor substrate (IRS)-1-bound phosphatidylinositol 3-kinase (PI 3-kinase) activation, is preserved, but insulin-stimulated protein kinase B (Akt) activation is markedly impaired. To assess a difference in acute insulin-stimulated production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], cells were labeled with [32P]orthophosphate, and glycerophosphoinositides were quantified by HPLC.

Reduction of O-GlcNAc protein modification does not prevent insulin resistance in 3T3-L1 adipocytes.

3T3-L1 adipocytes develop insulin-resistant glucose transport upon preincubation with high (25 mM) glucose, provided that insulin (0.6 nM) is included, Akt activation is impaired, and high glucose and insulin act synergistically. Considerable evidence suggests that increased glucose flux via the hexosamine biosynthesis pathway enhances the O-GlcNAc modification (O-GlcNAcylation) of some critical protein(s) that may contribute to insulin resistance.

Glucose, dexamethasone, and the unfolded protein response regulate TRB3 mRNA expression in 3T3-L1 adipocytes and L6 myotubes.

Tribbles 3 (TRB3) is a recently recognized atypical inactive kinase that negatively regulates Akt activity in hepatocytes, resulting in insulin resistance. Recent reports link TRB3 to nutrient sensing and regulation of cell survival under stressful conditions. We studied the regulation of TRB3 by glucose, insulin, dexamethasone (Dex), and the unfolded protein response (UPR) in 3T3-L1 adipocytes and in L6 myotubes.

At therapeutic concentrations, olanzapine does not affect basal or insulin-stimulated glucose transport in 3T3-L1 adipocytes.

The newer, atypical antipsychotic drugs have improved the treatment of schizophrenia and are widely used. A disadvantage is that they increase food intake, promote weight gain and may facilitate development of diabetes. The mechanism of the latter effect is controversial.

Risk for severe group A streptococcal disease among patients' household contacts.

From January 1997 to April 1999, we determined attack rates for cases of invasive group A streptococcal (GAS) disease in household contacts of index patients using data from Active Bacterial Core Surveillance sites. Of 680 eligible index-patient households, 525 (77.2%) were enrolled in surveillance.

Enhanced O-GlcNAc protein modification is associated with insulin resistance in GLUT1-overexpressing muscles.

O-linked glycosylation on Ser/Thr with single N-acetylglucosamine (O-GlcNAcylation) is a reversible modification of many cytosolic/nuclear proteins, regulated in part by UDP-GlcNAc levels. Transgenic (T) mice that overexpress GLUT1 in muscle show increased basal muscle glucose transport that is resistant to insulin stimulation. Muscle UDP-GlcNAc levels are increased.

Defective Akt activation is associated with glucose- but not glucosamine-induced insulin resistance.

Unlabelled: 3T3-L1 adipocytes develop insulin-resistant glucose transport upon preincubation with high glucose or glucosamine, provided insulin (0.6 nM) is present during preincubation. Insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol (PI) 3-kinase activity is unaffected (30).

Insulin acutely regulates Munc18-c subcellular trafficking: altered response in insulin-resistant 3T3-L1 adipocytes.

Preincubation of 3T3-L1 adipocytes in high glucose or glucosamine decreases acute insulin (100 nm)-stimulated glucose transport provided that insulin (0.6 nm) is included during preincubation. GLUT4 expression is unchanged (Nelson, B.