The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.

Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from Burkholderia cenocepacia.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a key enzyme in endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via the mevalonate pathway in other eukaryotes, archaea and some eubacteria. In most organisms that express this enzyme, it catalyzes the NAD(P)H-dependent reduction of HMG-CoA to mevalonate. We have cloned and characterized the 6x-His-tagged HMGR from the opportunistic lung pathogen Burkholderia cenocepacia. Kinetic characterization shows that the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme. This hypothesis is supported by the fact that the Burkholderia cenocepacia genome lacks the genes for the downstream enzymes of the mevalonate pathway. The enzyme exhibits positive cooperativity toward the substrates of the reductive reaction, but the oxidative reaction exhibits unusual double-saturation kinetics, distinctive among characterized HMG-CoA reductases. The unusual kinetics may arise from the presence of multiple active oligomeric states, each with different Vmax values.

Impact of malnutrition and nutrition support in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Malnutrition is prevalent in patients with inflammatory bowel disease (IBD) and has been associated with worse clinical outcomes. AIMS: This observational study examines trends in protein-calorie malnutrition (PCM) amongst hospitalised IBD and non-IBD patients, and the association between (1) malnutrition and (2) nutrition support and hospitalisation outcomes. METHODS: We queried the Nationwide Readmissions Database from 2010 to 2018 for hospitalisations with and without IBD. Amongst patients with IBD and concurrent PCM, we identified those who received nutrition support. Multivariable Cox proportional hazards and Kaplan-Meier analyses evaluated the associations between PCM and nutrition support and readmission and mortality. Multiple linear regression described the association between compared variables and length of stay (LOS) and total hospitalisation costs. RESULTS: This study included 1,216,033 patients (1,820,023 hospitalisations) with Crohn's disease (CD), 832,931 patients (1,089,853 hospitalizations) with ulcerative colitis (UC) and 240,488,656 patients (321,220,427 hospitalisations) without IBD. Admitted IBD patients were 2.9-3.1 times more likely to have PCM than non-IBD patients. IBD patients with PCM had a higher risk of readmission and mortality, as well as longer LOS and higher hospitalisation costs. Nutrition support (parenteral and enteral) was associated with a reduced risk of readmission, but higher mortality increased LOS and higher total hospitalisation costs. CONCLUSIONS: Malnutrition in hospitalised IBD patients remains an important contributor to readmission, mortality, LOS and healthcare costs. Providing nutrition support to IBD patients may reduce the risk of readmission. Further studies are needed to evaluate the role of nutrition support amongst hospitalised IBD patients to optimise disease and healthcare outcomes.

Hepatitis C Virus Treatment in Patients With Chronic Kidney Disease and in Kidney Transplant Recipients.

An important interplay exists between hepatitis C virus (HCV) infection and chronic kidney disease (CKD). HCV infection is associated with an increased risk of morbidity and mortality in patients coinfected with CKD, and patients with CKD have an increased risk of HCV infection. Direct-acting antiviral (DAA) agents have changed the landscape of treatment with excellent sustained virologic response rates and fewer side effects than previously seen. An increasing number of studies demonstrate that DAA agents are efficacious and safe both in patients on dialysis and in patients who have undergone kidney transplantation. This article reviews the current literature on approved DAA agents for the treatment of HCV infection in patients on dialysis and in kidney transplant recipients.

Avian Flu pandemic in the United States. The Sanitec Industry's solution.

On the basis of the extensive testing of the Sanitec Industries, Inc. waste management system by the North Carolina State University, the authors of this Editorial strongly recommend the immediate implementation of the Sanitec medical waste disinfection system throughout the United States to prevent the potential pandemic of the Avian Flu viral infection.