Crisis recovery in surgery: Error management and problem solving in safety-critical situations.

BACKGROUND: Surgical crises, both clinical and executive, carry risk of harm to patients, staff, and organizations. Once stabilized and contained, crisis recovery requires complex decision-making and problem-solving to address primary failures (errors) and their consequences. In contrast to other safety-critical professions, surgeons may lack access to crisis recovery strategies and tools that go beyond the technical aspects of clinical practice. This study aims to develop a framework for surgical crisis recovery based on problem-solving interventions used by pilots in commercial aviation. METHODS: This study undertook observational fieldwork, semistructured interviews, and focus groups with senior airline pilots and health care safety experts. Thematic analysis using the framework method identified key interventions applicable to surgical crisis recovery. Subsequently, expert group consensus adapted and content validated this model for clinical use. RESULTS: Qualitative data from 22 aviation and health care safety experts informed surgical crisis resolution. This consisted of 3 strategies: (1) building cognitive capacity by improving situational awareness and workload management; (2) using checklists in abnormal situations to implement emergency operating procedures; (3) undertaking structured decision-making using analysis-based problem-solving cycles (eg, T-DODAR framework). Twelve tools were validated and adapted to aid implementation of these strategies. CONCLUSION: Once stabilized, surgical crises may be resolved using 3 sequential strategies derived from commercial aviation.

Short-term effects of very low dose cadmium feeding on copper, manganese and iron homeostasis: A gastropod perspective.

The available information on the interplay between low-dose cadmium intake and copper, manganese, and iron homeostasis in invertebrates is limited. We have currently studied the accumulation of these trace metals in the hepatopancreas of adult snails, Cantareus aspersus, following 14 and 28 days of exposure to low doses of dietary cadmium, up to 1 mg/kg dw (dry weight). The cadmium dose, but not the duration of exposure, had a significant effect on hepatopancreas copper deposition, the values being significantly elevated compared to controls. A significant peak in manganese levels at 14 days was found in snails administered the lowest cadmium dose. These increases occurred even in the absence of cadmium increase in the hepatopancreas. Our data suggest that low dose cadmium feeding can produce a transient disturbance in hepatopancreas copper and manganese homeostasis. Such responses may serve as early biomarkers of physiological changes occurring during the initial stages of cadmium intoxication.

Clinical Significance of Measuring Global Hydroxymethylation of White Blood Cell DNA in Prostate Cancer: Comparison to PSA in a Pilot Exploratory Study.

This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP. We observed a wider heterogeneity in 5hmC content in all of the prostate pathologies analyzed when compared to the healthy age-matched controls. When compared to blood levels of prostate-specific antigen (PSA), this 5hmC-based biomarker had a lower performance in PCa detection than the use of a PSA cut-off of 2.5 nanograms per milliliter (ng/mL). Above this threshold, however, it delineated almost three quarters of PCa patients from controls and patients with other prostate pathologies. Overall, genome-wide 5hmC content of WBC DNA appears to be applicable for detecting non-cancerous prostate diseases, rather than PCa. Our results also suggest a potential clinical usefulness of complementing PSA as a PCa marker by the addition of a set of hydroxymethylation markers in the blood, but further studies are necessary to confirm these findings.

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas.

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics.

Data on expression of lipoxygenases-5 and -12 in the normal and acetaminophen-damaged liver.

Here we present additional data on the expression of lipoxygenases -5 and -12 in the normal and acetaminophen-damaged liver, which are associated with our manuscript recently published in Chemico-Biological Interactions on lipid metabolism and eicosanoid signaling pathways involved in acetaminophen-induced liver damage in a mouse model (http://dx.doi.org/10.1016/j.cbi.2015.10.019 [1]). It has been demonstrated that the expression of lipoxygenase-5 and leukotriene formation are increased in the livers of rats with carbon tetrachloride (CCl4)-induced cirrhosis (http://dx.doi.org/10.1053/gast.2000.17831 [2]). In addition, the lipoxygenase-12 is known to be expressed in the resident macrophage population of the liver (http://dx.doi.org/10.1016/S0014-5793(99)00396-8 [3]). Mice were injected with acetaminophen, and at 48 h their livers were processed for immunohistochemistry with anti-mouse lipoxygenase-5 and -12 antibodies. At the same time point, the RNA was also extracted from the liver to assess the expression of lipoxygenase-5 and -12 genes via qPCR analysis. Our results show that lipoxygenase-5 expression, but not that of lipoxygenase-12, changes significantly in the acetominophen-damaged liver.

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.

Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc.

Acetaminophen-induced liver injury: Implications for temporal homeostasis of lipid metabolism and eicosanoid signaling pathway.

Acetaminophen is a commonly used drug that induces serious hepatotoxicity when overdosed, leading to increased levels of serum aminotransferases. However, little knowledge exists linking acetaminophen to liver free fatty acids and the eicosanoid-mediated signaling pathway. To this end, adult NMRI mice injected with a dose of 400 mg/kg acetaminophen were monitored for one week post-treatment. Consistent changes were observed in serum transaminases, profile of hepatic free fatty acids, expression of cyclooxygenase, elongase, lipogenesis, and lipolysis genes; as well as in expression patterns of cyclooxygenase-1 and -2 in the liver. Both linoleic acid and arachidonic acid--substrates in eicosanoid biosynthesis--were significantly influenced by overdose, and the latter peaked first among the free fatty acids examined here. There was a close similarity between the temporal dynamics of linoleic acid and aspartate aminotransferases. Moreover, serum transaminases were reduced by cyclooxygenase-2 inhibitors, but not by cyclooxygenase-1 inhibitors. Our results hence attest to the hazard of acetaminophen overdose on the temporal homeostasis of hepatic concentrations of free fatty acids and expression of key genes underlying liver lipid metabolism. There is also evidence for activation of a cyclooxygenase-mediated signaling pathway, especially the cyclooxygenase 2-prostanoid pathway, during acetaminophen-induced liver injury. Therefore, the results of the present study should provide valuable information to a wide audience, working to understand the health hazard of this drug and the implications of the eicosanoid signaling pathway in liver pathophysiology.

Impact of soil cadmium on land snails: a two-stage exposure approach under semi-field conditions using bioaccumulative and conchological end-points of exposure.

Land snails are highly tolerant to cadmium exposure and are able to accumulate soil cadmium independently of food ingestion. However, little information exists on the kinetics of cadmium retention in terrestrial gastropods exposed to an increase in the soil cadmium content, over time. There is also little knowledge about how exposure to cadmium-polluted soils influences shell growth and architecture. In this context, we examined cadmium accumulation in the hepatopancreas and shell of juvenile Cantareus aspersus exposed to elevating high levels of cadmium in soil. Also, the toxicity of cadmium to snails was assessed using a range of conchological endpoints, including shell height, width, volume, allometry and integrity. Test snails, aged three months, were reared under semi-field conditions, fed an uncontaminated diet and exposed first, for a period of 30 days, to a series of soil cadmium concentrations, and then, for a second period of 30 days, to soils with higher cadmium content. Cadmium showed a dose-dependent accumulation in both the hepatopancreas and shell. The kinetics of cadmium retention in the hepatopancreas of snails previously exposed to cadmium-spiked soils was significantly influenced by a new exposure event. The shell was not a relevant bioaccumulator for soil cadmium. Under the present experimental conditions, only high cadmium exposure significantly affected either the shell growth or snail survival. There was no consistent effect on shell allometry, but the shell integrity, especially in rapidly growing parts, appeared to be affected by high cadmium exposure. Our results attest to the value of hepatopancreas for describing cadmium retention in land snails and to the difficulty of using conchological parameters in field surveys for estimating the environmental hazard of soil cadmium.

Soil manganese enrichment from industrial inputs: a gastropod perspective.

Manganese is one of the most abundant metal in natural environments and serves as an essential microelement for all living systems. However, the enrichment of soil with manganese resulting from industrial inputs may threaten terrestrial ecosystems. Several studies have demonstrated harmful effects of manganese exposure by cutaneous contact and/or by soil ingestion to a wide range of soil invertebrates. The link between soil manganese and land snails has never been made although these invertebrates routinely come in contact with the upper soil horizons through cutaneous contact, egg-laying, and feeding activities in soil. Therefore, we have investigated the direct transfer of manganese from soils to snails and assessed its toxicity at background concentrations in the soil. Juvenile Cantareus aspersus snails were caged under semi-field conditions and exposed first, for a period of 30 days, to a series of soil manganese concentrations, and then, for a second period of 30 days, to soils with higher manganese concentrations. Manganese levels were measured in the snail hepatopancreas, foot, and shell. The snail survival and shell growth were used to assess the lethal and sublethal effects of manganese exposure. The transfer of manganese from soil to snails occurred independently of food ingestion, but had no consistent effect on either the snail survival or shell growth. The hepatopancreas was the best biomarker of manganese exposure, whereas the shell did not serve as a long-term sink for this metal. The kinetics of manganese retention in the hepatopancreas of snails previously exposed to manganese-spiked soils was significantly influenced by a new exposure event. The results of this study reveal the importance of land snails for manganese cycling in terrestrial biotopes and suggest that the direct transfer from soils to snails should be considered when precisely assessing the impact of anthropogenic Mn releases on soil ecosystems.

A novel exploratory chemometric approach to environmental monitorring by combining block clustering with Partial Least Square (PLS) analysis.

BACKGROUND: Given the serious threats posed to terrestrial ecosystems by industrial contamination, environmental monitoring is a standard procedure used for assessing the current status of an environment or trends in environmental parameters. Measurement of metal concentrations at different trophic levels followed by their statistical analysis using exploratory multivariate methods can provide meaningful information on the status of environmental quality. In this context, the present paper proposes a novel chemometric approach to standard statistical methods by combining the Block clustering with Partial least square (PLS) analysis to investigate the accumulation patterns of metals in anthropized terrestrial ecosystems. The present study focused on copper, zinc, manganese, iron, cobalt, cadmium, nickel, and lead transfer along a soil-plant-snai food chain, and the hepatopancreas of the Roman snail (Helix pomatia) was used as a biological end-point of metal accumulation. RESULTS: Block clustering deliniates between the areas exposed to industrial and vehicular contamination. The toxic metals have similar distributions in the nettle leaves and snail hepatopancreas. PLS analysis showed that (1) zinc and copper concentrations at the lower trophic levels are the most important latent factors that contribute to metal accumulation in land snails; (2) cadmium and lead are the main determinants of pollution pattern in areas exposed to industrial contamination; (3) at the sites located near roads lead is the most threatfull metal for terrestrial ecosystems. CONCLUSION: There were three major benefits by applying block clustering with PLS for processing the obtained data: firstly, it helped in grouping sites depending on the type of contamination. Secondly, it was valuable for identifying the latent factors that contribute the most to metal accumulation in land snails. Finally, it optimized the number and type of data that are best for monitoring the status of metallic contamination in terrestrial ecosystems exposed to different kinds of anthropic polution.

Use of enzymatic tools for biomonitoring inorganic pollution in aquatic sediments: a case study (Bor, Serbia).

BACKGROUND: Sediment bacterial communities are key players in biogeochemical cycling of elements in the aquatic environment. Copper mining, smelting, and processing operations located in Bor area (Serbia) are major environmental hot spots in the lower Danube Basin and Western Balkans. In the present study, we evaluate the influence of trace element (TE) concentration in sediments and physico-chemical properties of water on sediment microbial communities in water streams adjacent to the Copper Smelter Complex Bor (RTB Bor, Serbia). The degree to which metabolic activities of bacterial biota inhabiting differently polluted sites is inhibited by inorganic pollution were compared using selected enzymatic bioindicators. RESULTS: Cu, Zn, Pb, and As concentrations systematically exceeded the target values for metal loadings in aquatic sediments. Water electrical conductivity (WEC) followed the same pattern of spatial variation, irrespective of season. Interestingly, the most intense enzymatic activity occurred at the reference site although this site showed the greatest TE levels in aquatic sediments. Catalase activity (CA), potential dehydrogenase activity (PDA), actual dehydrogenase activity (ADA), urease activity (UA), and phosphatase activity (PA) in aquatic sediments displayed heterogeneous patterns of spatio-temporal variation. Inorganic pollution greatly affected CA, ADA, and PDA, but much less so UA and PA. Canonical correlation analysis showed that pH and WEC were the strongest determinants of enzymatic activity in bacterial biota, with the latter variable being reversely correlated with the enzymatic indicator of sediment quality (EISQ). The median values of EISQ increased with distance from the major sources of pollution. In addition, it was found that sites with different degrees of inorganic pollution can be appropriately classified by applying cluster analysis to EISQ, TE levels in sediments, and physico-chemical properties of water. CONCLUSIONS: Because EISQ can precisely identify changes in overall enzymatic activity of sediment bacterial communities, this enzymatic bioindicator has a great potential for biomonitoring the current status of inorganic pollution in aquatic ecosystems.

Bioaccumulative and conchological assessment of heavy metal transfer in a soil-plant-snail food chain.

BACKGROUND: Copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) can pose serious threats to environmental health because they tend to bioaccumulate in terrestrial ecosystems. We investigated under field conditions the transfer of these heavy metals in a soil-plant-snail food chain in Banat area, Romania. The main goal of this paper was to assess the Roman snail (Helix pomatia) usefulness in environmental monitoring as bioindicator of heavy metal accumulation. Eight sampling sites, selected by different history of heavy metal (HM) exposure, were chosen to be sampled for soil, nettle leaves, and newly matured snails. This study also aimed to identify the putative effects of HM accumulation in the environment on phenotypic variability in selected shell features, which included shell height (SH), relative shell height (RSH), and whorl number (WN). RESULTS: Significantly higher amounts of HMs were accumulated in snail hepatopancreas and not in foot. Cu, Zn, and Cd have biomagnified in the snail body, particularly in the hepatopancreas. In contrast, Pb decreased when going up into the food chain. Zn, Cd, and Pb correlated highly with each other at all levels of the investigated food chain. Zn and Pb exhibited an effective soil-plant transfer, whereas in the snail body only foot Cu concentration was correlated with that in soil. There were significant differences among sampling sites for WN, SH, and RSH when compared with reference snails. WN was strongly correlated with Cd and Pb concentrations in nettle leaves but not with Cu and Zn. SH was independent of HM concentrations in soil, snail hepatopancreas, and foot. However, SH correlated negatively with nettle leaves concentrations for each HM except Cu. In contrast, RSH correlated significantly only with Pb concentration in hepatopancreas. CONCLUSIONS: The snail hepatopancreas accumulates high amounts of HMs, and therefore, this organ can function as a reliable biomarker for tracking HM bioavailability in soil. Long-term exposure to HMs via contaminated food might influence the variability of shell traits in snail populations. Therefore, our results highlight the Roman snail (Helix pomatia) potential to be used in environmental monitoring studies as bioindicator of HM pollution.

Post-infectious pseudoaneurysm after coronary angioplasty using drug eluting stents.

Infections at the site of coronary stents are uncommon, and believed to be the result of either direct stent contamination at the time of delivery, or from transient bacteraemia from the access site. A case of pseudoaneurysm ("mycotic" aneurysm) of the left anterior descending coronary artery, due to infection with Staphylococcus aureus after paclitaxel-eluting stents implantation is presented.

K5 D328E: a novel missense mutation in the linker 12 domain of keratin 5 associated with epidermolysis bullosa simplex (Weber-Cockayne).

A novel missense mutation was detected in the L12 region of keratin 5 (K5) in a Slovene family diagnosed with a Weber-Cockayne variant of epidermolysis bullosa simplex (EBS). Direct sequencing identified a heterozygous GAC to GAA substitution altering codon 328 of K5 from Asp to Glu in all affected family members, while no mutation was observed either in the healthy individual or the 50 unrelated control samples. Asp(328) of K5 (position 12 in the L12 domain) is remarkably conserved among all type II keratins. K5 L12:D12E is the third mutation found to affect this residue in K5-related EBS, indicating the importance of Asp(328) for K5 structure and the dramatic effect that fine changes can have on keratin intermediate filament integrity.

Lack of efficacy of 6-week treatment with oral terbinafine for tinea capitis due to Microsporum canis in children.

Twenty-two children aged 2 to 9 years with noninflammatory tinea capitis due to Microsporum canis were evaluated in an open clinical pilot study run from January 1994 to July 1995. Each child was given oral terbinafine according to body weight for 6 weeks. Mycologic evaluation was done at the end of treatment and after follow-up periods of 4 and 8 weeks. None of the patients achieved complete mycologic cure by the end of the treatment period. Four weeks later complete mycologic cure was established in nine patients, and on final evaluation in seven. The treatment was very well tolerated by all the children. No systemic adverse effects were noted. According to our data, a 6-week course of oral terbinafine is inadequate for tinea capitis due to M. canis in children. Further study is needed to determine the most appropriate duration of therapy.