Survival curve for “ever PPIH” versus patients without hypomagnesaemia.

<p>Survival curve for “ever PPIH” versus patients without hypomagnesaemia.</p

Odds ratios for ever hypomagnesemia in patients on PPI compared to those who are not, separated according to CKD stage.

<p>Odds ratios for ever hypomagnesemia in patients on PPI compared to those who are not, separated according to CKD stage.</p

Survival curve for “mean PPIH” versus patients without hypomagnesaemia.

<p>Survival curve for “mean PPIH” versus patients without hypomagnesaemia.</p

Average serum magnesium increases in patients as CKD progresses in patients NOT on a proton pump inhibitor.

<p>This rise in not observed in patients on PPI (error bars demonstrate the standard deviation).</p

Odds ratios for mean and ever hypomagnesaemia, demonstrating univariate results for PPI versus not on PPI, and the results of a multivariate model.

<p>Odds ratios for mean and ever hypomagnesaemia, demonstrating univariate results for PPI versus not on PPI, and the results of a multivariate model.</p

Surgery and opioids: evidence-based expert consensus guidelines on the perioperative use of opioids in the United Kingdom

There are significant concerns regarding prescription and misuse of prescription opioids in the perioperative period. TheFaculty of Pain Medicine at the Royal College of Anaesthetists have produced this evidence-based expert consensusguideline on surgery and opioids along with the Royal College of Surgery, Royal College of Psychiatry, Royal College ofNursing, and the British Pain Society. This expert consensus practice advisory reproduces the Faculty of Pain Medicineguidance. Perioperative stewardship of opioids starts with judicious opioid prescribing in primary and secondary care.Before surgery, it is important to assess risk factors for continued opioid use after surgery and identify those with chronicpain before surgery, some of whom may be taking opioids. A multidisciplinary perioperative care plan that includes aprehabilitation strategy and intraoperative and postoperative care needs to be formulated. This may need the input of apain specialist. Emphasis is placed on optimum management of pain pre-, intra-, and postoperatively. The use ofimmediate-release opioids is preferred in the immediate postoperative period. Attention to ensuring a smooth caretransition and communication from secondary to primary care for those taking opioids is highlighted. For opioid-naivepatients (patients not taking opioids before surgery), no more than 7 days of opioid prescription is recommended.Persistent use of opioid needs a medical evaluation and exclusion of chronic post-surgical pain. The lack of grading of theevidence of each individual recommendation remains a major weakness of this guidance; however, evidence supportingeach recommendation has been rigorously reviewed by experts in perioperative pain management.</div

Ambient Nonmethane Hydrocarbon Levels Along Colorado’s Northern Front Range: Acute and Chronic Health Risks

Oil and gas (O&G) facilities emit air pollutants that are potentially a major health risk for nearby populations. We characterized prenatal through adult health risks for acute (1 h) and chronic (30 year) residential inhalation exposure scenarios to nonmethane hydrocarbons (NMHCs) for these populations. We used ambient air sample results to estimate and compare risks for four residential scenarios. We found that air pollutant concentrations increased with proximity to an O&G facility, as did health risks. Acute hazard indices for neurological (18), hematological (15), and developmental (15) health effects indicate that populations living within 152 m of an O&G facility could experience these health effects from inhalation exposures to benzene and alkanes. Lifetime excess cancer risks exceeded 1 in a million for all scenarios. The cancer risk estimate of 8.3 per 10 000 for populations living within 152 m of an O&G facility exceeded the United States Environmental Protection Agency’s 1 in 10 000 upper threshold. These findings indicate that state and federal regulatory policies may not be protective of health for populations residing near O&G facilities. Health risk assessment results can be used for informing policies and studies aimed at reducing and understanding health effects associated with air pollutants emitted from O&G facilities

The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

<div><p>The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen <i>Pseudomonas aeruginosa</i>. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with <i>P. aeruginosa</i> agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. <i>P. aeruginosa</i> mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.</p></div

Agmatine induces NF-κB in animal models of inflammation.

<p>HLL NF-κB reporter mice were challenged intratracheally with PBS (unfilled) or agmatine (filled) and luminescence was measured at the specified timepoints after injection as described in the methods. Each mouse served as its own control and the relative change per mouse compared to background luminescence is plotted on the y-axis. In (A) there are 3 mice in the PBS group and 5 mice in the Ag group and luminescence was measured over the chest only as shown in (B). This experiment was replicated on 2 other occasions with similar results. Panel (B) shows representative images of individual mice in these studies. Independent t-tests were used between groups of mice with relevant comparisons shown. All error bars represent SEM. Independent t-tests used between groups. *<i>P</i><0.05.</p

Agmatine metabolic phenotype of clinical bacterial isolates from sputum.

<p>Supernatant agmatine was measured by UPLC-MS/MS after 24 h growth in RPMI without (white bars) or with (black bars) 10 µM agmatine. PA- <i>P. aeruginosa</i>, AX- <i>Achromobacter xyloxidans</i>, BC- <i>Burkholderia cepacia</i>, SA-<i>Staphylococcus aureus</i>, SM- <i>Serratia marcesens</i>, PA14-WT <i>P. aeruginosa</i> laboratory strain used in these studies, PA14-neutral mutant with genotype Δ<i>speA</i>, <i>aguA:gm</i>, Δ<i>agu2ABCA</i>' neither creates nor degrades agmatine, PA14-hypersecretor mutant with genotype <i>aguA::gm</i>, <i>Δagu2ABCA</i>', creates but cannot degrade agmatine. Bars represent average measured values of triplicate analyses by UPLC-MS/MS. Error bars represent SEM.</p