Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage.

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.

Site-specific protein modifications through pyrroline-carboxy-lysine residues.

Pyrroline-carboxy-lysine (Pcl) is a demethylated form of pyrrolysine that is generated by the pyrrolysine biosynthetic enzymes when the growth media is supplemented with D-ornithine. Pcl is readily incorporated by the unmodified pyrrolysyl-tRNA/tRNA synthetase pair into proteins expressed in Escherichia coli and in mammalian cells. Here, we describe a broadly applicable conjugation chemistry that is specific for Pcl and orthogonal to all other reactive groups on proteins. The reaction of Pcl with 2-amino-benzaldehyde or 2-amino-acetophenone reagents proceeds to near completion at neutral pH with high efficiency. We illustrate the versatility of the chemistry by conjugating Pcl proteins with poly(ethylene glycol)s, peptides, oligosaccharides, oligonucleotides, fluorescence, and biotin labels and other small molecules. Because Pcl is genetically encoded by TAG codons, this conjugation chemistry enables enhancements of the pharmacology and functionality of proteins through site-specific conjugation.

Family presence during cardiopulmonary resuscitation: using evidence-based knowledge to guide the advanced practice nurse in developing formal policy and practice guidelines.

PURPOSE: To provide advanced practice nurses (APNs) with the best available evidence for implementation of policies and procedures to allow family presence during cardiopulmonary resuscitation (CPR) in the acute care environment. DATA SOURCES: A comprehensive review of research-based articles from Ebsco Host, CINAHL, Pre-CINAHL, and Medline Plus, as well as statement alerts from nursing credentialing bodies, and practice guidelines were reviewed. Kolcaba's Theory of Comfort and Lewin's Three Step Change Theory provide a framework for implementation of formal policies and procedures. CONCLUSIONS: Best available evidence showed more support in favor of allowing families at the bedside during CPR. Implementation of policies and procedures allowing family presence enables facilities to change and grow in a holistic and family-oriented atmosphere. IMPLICATIONS FOR PRACTICE: With this evidence-based knowledge the APN will be able to disseminate information to facilitate collaborative change in current practices surrounding staff education, decision making, and self-governance. The APN can then address controversial changes when developing formal policies and procedures, which will increase patient satisfaction and outcomes.

Application of the social ecological model in folic acid public health initiatives.

All women of childbearing age who are capable of becoming pregnant should consume 0.4 mg/400 microg of folic acid daily. Folic acid decreases the incidence of neural tube defects in newborns. Despite continued public health initiatives, many women still do not consume the recommended daily requirement. This article analyzes the use of the social ecological model in folic acid public health initiatives and emphasizes assessing the outcomes of such initiatives.