Respiratory and circulatory insufficiency during emergent long-distance critical care interhospital transports to tertiary care in a sparsely populated region: a retrospective analysis of late mortality risk.

OBJECTIVES: To test if impaired oxygenation or major haemodynamic instability at the time of emergency intensive care transport, from a smaller admitting hospital to a tertiary care centre, are predictors of long-term mortality. DESIGN: Retrospective observational study. Impaired oxygenation was defined as oxyhaemoglobin %-inspired oxygen fraction ratio (S/F ratio)<100. Major haemodynamic instability was defined as a need for treatment with norepinephrine infusion to sustain mean arterial pressure (MAP) at or above 60 mm Hg or having a mean MAP <60. Logistic regression was used to assess mortality risk with impaired oxygenation or major haemodynamic instability. SETTING: Sparsely populated Northern Sweden. A fixed-wing interhospital air ambulance system for critical care serving 900 000 inhabitants. PARTICIPANTS: Intensive care cases transported in fixed-wing air ambulance from outlying hospitals to a regional tertiary care centre during 2000-2016 for adults (16 years old or older). 2142 cases were included. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause mortality at 3 months after transport was the primary outcome, and secondary outcomes were all-cause mortality at 1 and 7 days, 1, 6 and 12 months. RESULTS: S/F ratio <100 was associated with increased mortality risk compared with S/F>300 at all time-points, with adjusted OR 6.3 (2.5 to 15.5, p<0.001) at 3 months. Major haemodynamic instability during intensive care unit (ICU) transport was associated with increased adjusted OR of all-cause mortality at 3 months with OR 2.5 (1.8 to 3.5, p<0.001). CONCLUSION: Major impairment of oxygenation and/or major haemodynamic instability at the time of ICU transport to get to urgent tertiary intervention is strongly associated with increased mortality risk at 3 months in this cohort. These findings support the conclusion that these conditions are markers for many fold increase in risk for death notable already at 3 months after transport for patients with these conditions.

Total Mission Time and Mortality in a Regional Interhospital Critical Care Transport System: A Retrospective Observational Study.

OBJECTIVE: We assessed the mortality risk related to the time for intensive care unit transport in a geographically large regional health care system. METHODS: Patient-level data from critical care ambulance missions were analyzed for 2,067 cases, mission time, and relevant patient factors. Mission time was used as a surrogate for the "distance" to tertiary care, and mortality at 7 days and other intervals was assessed. RESULTS: No increased mortality risk was found at 7 days in an unadjusted regression analysis (odds ratio = 1.00; range, 0.999-1.002; P = .66). In a secondary analysis, an increased mortality risk was observed in longer mission time subgroups and at later mortality assessment intervals (> 375 mission minutes and 90-day mortality; adjusted hazard ratio = 1.56; range, 1.07-2.28; P = .02). Negative changes in oxygenation and hemodynamic status and transport-related adverse events were associated with the longest flight times. Measurable but small changes during flight were noted for mean arterial pressure and oxygenation. CONCLUSION: The main finding was that there was no overall difference in mortality risk based on mission time. We conclude that transport distances or accessibility to critical care in the tertiary care center in a geographically large but sparsely populated region is not clearly associated with mortality risk.

Major lead exposure from hunting ammunition in eagles from Sweden.

Exposure to lead (Pb) from ammunition in scavenging and raptorial birds has achieved worldwide recognition based on incidences of lethal poisoning, but exposure implies also sublethal levels with potential harmful effects. Background and elevated Pb levels in liver from 116 golden eagles (GE, Aquila chrysaetos) and 200 white-tailed sea eagles (WTSE, Haliaeetus albicilla) from Sweden 2003-2011 are here examined, with supporting data from a previous WTSE report and eagle owl (EO, Bubu bubo) report. GE and WTSE display seasonal patterns, with no Pb level exceeding a generally accepted threshold for subclinical effects during summer but strongly elevated levels from October. Fledged juveniles show significantly lower levels than all other age classes, but reach levels found in older birds in autumn after the start of hunting seasons. Pb levels in EO (non-scavenger) show no seasonal changes and indicate no influence from ammunition, and are close to levels observed in juvenile eagles before October. In all, 15% WTSE and 7% GE were lethally poisoned. In areas with high-exposure to hunting ammunition, 24% of WTSE showed lethal Pb levels, compared to 7% in both eagle species from low-exposure areas. Lethal poisoning of WTSE remained as frequent after (15%) as before (13%) a partial ban on use of Pb-based shotgun ammunition over shallow waters (2002). Pb levels increased significantly in WTSE 1981-2011, in contrast to other biota from the same period. A significant decrease of Pb in WTSE liver occurred below a threshold at 0.25 µg/g (dry weight), exceeded by 81% of the birds. Trend patterns in Pb isotope ratios lend further support to this estimated cut-off level for environmental background concentrations. Pb from spent ammunition affects a range of scavenging and predatory species. A shift to Pb-free ammunition to save wildlife from unnecessary harm is an important environmental and ethical issue.

Bioconcentration of Several Series of Cationic Surfactants in Rainbow Trout.

Cationic surfactants have a strong affinity to sorb to phospholipid membranes and thus possess an inherent potential to bioaccumulate, but there are few measurements of bioconcentration in fish. We measured the bioconcentration of 10 alkylamines plus two quaternary ammonium compounds in juvenile rainbow trout at pH 7.6, and repeated the measurements at pH 6.2 for 6 of these surfactants. The BCF of the amines with chain lengths ≤ C14 was positively correlated with chain length, increasing ∼0.5 log units per carbon. Their BCF was also pH dependent and approximately proportional to the neutral fraction of the amine in the water. The BCFs of the quaternary ammonium compounds showed no pH dependence and were >2 orders of magnitude less than for amines of the same chain length at pH 7.6. This indicates that systemic uptake of permanently charged cationic surfactants is limited. The behavior of the quaternary ammonium compounds and the two C16 amines studied was consistent with previous observations that these surfactants accumulate primarily to the gills and external surfaces of the fish. At pH 7.6 the BCF exceeded 2000 L kg-1 for 4 amines with chains ≥ C13, showing that bioconcentration can be considerable for some longer chained cationic surfactants.

Temporal Changes in Concentrations of Lead and Other Trace Metals in Free-Ranging Eurasian Eagle Owls Bubo bubo in Sweden.

Patterns of lead and other trace metals were examined in 122 Eurasian eagle owls Bubo bubo found dead in Sweden in the period 1978-2013. Environmental lead (Pb) has decreased over recent decades from reduced anthropogenic emissions but mortality by Pb poisoning is still frequently reported for avian raptors and scavengers exposed to Pb ammunition. One objective here was to determine if Pb concentrations in a nocturnal non-scavenging raptor follow the general decline observed in other biota. Pb concentration in owl liver was significantly correlated with body weight, sex, latitude, longitude and season. Pb showed a significant decreasing trend towards north and west. Starved birds had significantly higher concentrations. Total Pb concentrations in liver averaged 0.179 µg g-1 dry weight (median 0.103) and decreased by 5.6% per year 1978-2013, or 5.3% after adjustment for confounding factors, similar to trends in other species. Among 14 other trace elements only antimony and arsenic showed decreasing trends. Lead isotope ratios 206Pb/207Pb and 208Pb/207Pb increased from 1.138 and 2.408 in 1978-1985 to 1.170 and 2.435 in 2010-2013, respectively, demonstrating that the decreasing Pb concentration in eagle owl is related to the phase-out of leaded gasoline in Europe, where Pb additives had much lower isotope ratios than natural lead in Swedish soils. Only one incidence of suspected Pb poisoning (40.7 µg g-1 in liver) was observed indicating that poisoning from ingestion of metallic lead is rare (< 1%) in eagle owl in Sweden, in contrast to what has been reported for eagles.

The Yersinia pseudotuberculosis Cpx envelope stress system contributes to transcriptional activation of rovM.

The Gram-negative enteropathogen Yersinia pseudotuberculosis possesses a number of regulatory systems that detect cell envelope damage caused by noxious extracytoplasmic stresses. The CpxA sensor kinase and CpxR response regulator two-component regulatory system is one such pathway. Active Cpx signalling upregulates various factors designed to repair and restore cell envelope integrity. Concomitantly, this pathway also down-regulates key determinants of virulence. In Yersinia, cpxA deletion accumulates high levels of phosphorylated CpxR (CpxR~P). Accumulated CpxR~P directly repressed rovA expression and this limited expression of virulence-associated processes. A second transcriptional regulator, RovM, also negatively regulates rovA expression in response to nutrient stress. Hence, this study aimed to determine if CpxR~P can influence rovA expression through control of RovM levels. We determined that the active CpxR~P isoform bound to the promoter of rovM and directly induced its expression, which naturally associated with a concurrent reduction in rovA expression. Site-directed mutagenesis of the CpxR~P binding sequence in the rovM promoter region desensitised rovM expression to CpxR~P. These data suggest that accumulated CpxR~P inversely manipulates the levels of two global transcriptional regulators, RovA and RovM, and this would be expected to have considerable influence on Yersinia pathophysiology and metabolism.

Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor.

BACKGROUND: Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. METHODOLOGY/PRINCIPAL FINDINGS: COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 µM; COX-2 (arachidonic acid) 20 µM; COX-2 (2-AG) 1 µM; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 µM; COX-2 (arachidonic acid) 10 µM; COX-2 (2-AG) 0.7 µM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 µM) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 µM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 µM). CONCLUSIONS/SIGNIFICANCE: Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.

Half a century of changing mercury levels in Swedish freshwater fish.

The variability of mercury (Hg) levels in Swedish freshwater fish during almost 50 years was assessed based on a compilation of 44 927 observations from 2881 waters. To obtain comparable values, individual Hg concentrations of fish from any species and of any size were normalized to correspond to a standard 1-kg pike [median: 0.69 mg kg⁻¹ wet weight (ww), mean ± SD: 0.84 ± 0.67 mg kg⁻¹ ww]. The EU Environmental Quality Standard of 0.02 mg kg⁻¹ was exceeded in all waters, while the guideline set by FAO/WHO for Hg levels in fish used for human consumption (0.5-1.0 mg kg⁻¹) was exceeded in 52.5 % of Swedish waters after 2000. Different trend analysis approaches indicated an overall long-term decline of at least 20 % during 1965-2012 but trends did not follow any consistent regional pattern. During the latest decade (2003-2012), however, a spatial gradient has emerged with decreasing trends predominating in southwestern Sweden.

Mercury concentrations in landlocked Arctic char (Salvelinus alpinus) from the Canadian Arctic. Part I: insights from trophic relationships in 18 lakes.

Concentrations of mercury (Hg) have increased slowly in landlocked Arctic char over a 10- to 15-year period in the Arctic. Fluxes of Hg to sediments also show increases in most Arctic lakes. Correlation of Hg with trophic level (TL) was used to investigate and compare biomagnification of Hg in food webs from lakes in the Canadian Arctic sampled from 2002 to 2007. Concentrations of Hg (total Hg and methylmercury [MeHg]) in food webs were compared across longitudinal and latitudinal gradients in relation to delta(13)C and delta(15)N in periphyton, zooplankton, benthic invertebrates, and Arctic char of varying size-classes. Trophic magnification factors (TMFs) were calculated for the food web in each lake and related to available physical and chemical characteristics of the lakes. The relative content of MeHg increased with trophic level from 4.3 to 12.2% in periphyton, 41 to 79% in zooplankton, 59 to 72% in insects, and 74 to 100% in juvenile and adult char. The delta(13)C signatures of adult char indicated coupling with benthic invertebrates. Cannibalism among char lengthened the food chain. Biomagnification was confirmed in all 18 lakes, with TMFs ranging from 3.5 +/- 1.1 to 64.3 +/- 0.8. Results indicate that TMFs and food chain length (FCL) are key factors in explaining interlake variability in biomagnification of [Hg] among different lakes.