Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Evaporative evolution of a Na–Cl–NO(3)–K–Ca–SO(4)–Mg–Si brine at 95°C: Experiments and modeling relevant to Yucca Mountain, Nevada

A synthetic Topopah Spring Tuff water representative of one type of pore water at Yucca Mountain, NV was evaporated at 95°C in a series of experiments to determine the geochemical controls for brines that may form on, and possibly impact upon the long-term integrity of waste containers and drip shields at the designated high-level, nuclear-waste repository. Solution chemistry, condensed vapor chemistry, and precipitate mineralogy were used to identify important chemical divides and to validate geochemical calculations of evaporating water chemistry using a high temperature Pitzer thermodynamic database. The water evolved toward a complex "sulfate type" brine that contained about 45 mol % Na, 40 mol % Cl, 9 mol % NO(3), 5 mol % K, and less than 1 mol % each of SO(4), Ca, Mg, ∑CO(2)(aq), F, and Si. All measured ions in the condensed vapor phase were below detection limits. The mineral precipitates identified were halite, anhydrite, bassanite, niter, and nitratine. Trends in the solution composition and identification of CaSO(4 )solids suggest that fluorite, carbonate, sulfate, and magnesium-silicate precipitation control the aqueous solution composition of sulfate type waters by removing fluoride, calcium, and magnesium during the early stages of evaporation. In most cases, the high temperature Pitzer database, used by EQ3/6 geochemical code, sufficiently predicts water composition and mineral precipitation during evaporation. Predicted solution compositions are generally within a factor of 2 of the experimental values. The model predicts that sepiolite, bassanite, amorphous silica, calcite, halite, and brucite are the solubility controlling mineral phases

Etiology of Childhood Bacteremia and Timely Antibiotics Administration in the Emergency Department

BACKGROUND: Bacteremia is now an uncommon presentation to the children’s emergency department (ED) but is associated with significant morbidity and mortality. Its evolving etiology may affect the ability of clinicians to initiate timely, appropriate antimicrobial therapy. METHODS: A retrospective time series analysis of bacteremia was conducted in the Alder Hey Children’s Hospital ED between 2001 and 2011. Data on significant comorbidities, time to empirical therapy, and antibiotic susceptibility were recorded. RESULTS: A total of 575 clinical episodes were identified, and Streptococcus pneumoniae (n = 109), Neisseria meningitidis (n = 96), and Staphylococcus aureus (n = 89) were commonly isolated. The rate of bacteremia was 1.42 per 1000 ED attendances (95% confidence interval: 1.31–1.53). There was an annual reduction of 10.6% (6.6%–14.5%) in vaccine-preventable infections, and an annual increase of 6.7% (1.2%–12.5%) in Gram-negative infections. The pneumococcal conjugate vaccine was associated with a 49% (32%–74%) reduction in pneumococcal bacteremia. The rate of health care–associated bacteremia increased from 0.17 to 0.43 per 1000 ED attendances (P = .002). Susceptibility to empirical antibiotics was reduced (96.3%–82.6%; P < .001). Health care–associated bacteremia was associated with an increased length of stay of 3.9 days (95% confidence interval: 2.3–5.8). Median time to antibiotics was 184 minutes (interquartile range: 63–331) and 57 (interquartile range: 27–97) minutes longer in Gram-negative bacteremia than in vaccine-preventable bacteremia. CONCLUSIONS: Changes in the etiology of pediatric bacteremia have implications for prompt, appropriate empirical treatment. Increasingly, pediatric bacteremia in the ED is health care associated, which increases length of inpatient stay. Prompt, effective antimicrobial administration requires new tools to improve recognition, in addition to continued etiological surveillance

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

Integrated photonic quantum gates for polarization qubits

Integrated photonic circuits have a strong potential to perform quantum information processing. Indeed, the ability to manipulate quantum states of light by integrated devices may open new perspectives both for fundamental tests of quantum mechanics and for novel technological applications. However, the technology for handling polarization encoded qubits, the most commonly adopted approach, is still missing in quantum optical circuits. Here we demonstrate the first integrated photonic Controlled-NOT (CNOT) gate for polarization encoded qubits. This result has been enabled by the integration, based on femtosecond laser waveguide writing, of partially polarizing beam splitters on a glass chip. We characterize the logical truth table of the quantum gate demonstrating its high fidelity to the expected one. In addition, we show the ability of this gate to transform separable states into entangled ones and vice versa. Finally, the full accessibility of our device is exploited to carry out a complete characterization of the CNOT gate through a quantum process tomography.Comment: 6 pages, 4 figure

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

TNF-α increases human melanoma cell invasion and migration in vitro: the role of proteolytic enzymes

Inflammatory mediators have been reported to promote malignant cell growth, invasion and metastatic potential. More specifically, we have recently reported that tumour necrosis factor alpha (TNF-a) increases melanoma cell attachment to extracellular matrix (ECM) substrates and invasion through fibronectin. In this study, we extend these investigations asking specifically whether the TNF-a effect on cell invasion and migration involves activation of proteolytic enzymes. We examined the effect of TNF-a on melanoma expression/activation of type IV gelatinases matrix metalloproteinases 2 and 9 (MMPs -2 and -9) and general proteolytic enzymes. Stimulation with TNF-a significantly increased both melanoma cell migration at 24 h ( þ 21%) and invasion through fibronectin ( þ 35%) but did not upregulate/activate the expression of latent MMP-2 constitutively produced by these cells and did not upregulate their general protease activity. However, the increased cell migration and invasion through fibronectin observed following stimulation with TNF-a were inhibited by the general protease inhibitor a2 macroglobulin. These findings suggest that the promigratory and proinvasive effect of TNF-a on this melanoma cell line may be mediated to some extent by induction of localised cell membrane-bound degradative enzyme activity, which is not readily detected in biochemical assays

Informed consent for MRI and fMRI research: Analysis of a sample of Canadian consent documents

<p>Abstract</p> <p>Background</p> <p>Research ethics and the measures deployed to ensure ethical oversight of research (e.g., informed consent forms, ethics review) are vested with extremely important ethical and practical goals. Accordingly, these measures need to function effectively in real-world research and to follow high level standards.</p> <p>Methods</p> <p>We examined approved consent forms for Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) studies approved by Canadian research ethics boards (REBs).</p> <p>Results</p> <p>We found evidence of variability in consent forms in matters of physical and psychological risk reporting. Approaches used to tackle the emerging issue of incidental findings exposed extensive variability between and within research sites.</p> <p>Conclusion</p> <p>The causes of variability in approved consent forms and studies need to be better understood. However, mounting evidence of administrative and practical hurdles within current ethics governance systems combined with potential sub-optimal provision of information to and protection of research subjects support other calls for more scrutiny of research ethics practices and applicable revisions.</p

Lifestyle physical activity among urban Palestinians and Israelis: a cross-sectional comparison in the Palestinian-Israeli Jerusalem risk factor study

<p>Abstract</p> <p>Background</p> <p>Urban Palestinians have a high incidence of coronary heart disease, and alarming prevalences of obesity (particularly among women) and diabetes. An active lifestyle can help prevent these conditions. Little is known about the physical activity (PA) behavior of Palestinians. This study aimed to determine the prevalence of insufficient PA and its socio-demographic correlates among urban Palestinians in comparison with Israelis.</p> <p>Methods</p> <p>An age-sex stratified random sample of Palestinians and Israelis aged 25-74 years living in east and west Jerusalem was drawn from the Israel National Population Registry: 970 Palestinians and 712 Israelis participated. PA in a typical week was assessed by the Multi-Ethnic Study of Atherosclerosis (MESA) questionnaire. Energy expenditure (EE), calculated in metabolic equivalents (METs), was compared between groups for moderate to vigorous-intensity physical activity (MVPA), using the Wilcoxon rank-sum test, and for domain-specific prevalence rates of meeting public health guidelines and all-domain insufficient PA. Correlates of insufficient PA were assessed by multivariable logistic modeling.</p> <p>Results</p> <p>Palestinian men had the highest median of MVPA (4740 METs-min_*wk^-1) compared to Israeli men (2,205 METs-min_*wk^-1<it>p </it>< 0.0001), or to Palestinian and Israeli women, who had similar medians (2776 METs-min_*wk^-1). Two thirds (65%) of the total MVPA reported by Palestinian women were derived from domestic chores compared to 36% in Israeli women and 25% among Palestinian and Israeli men. A high proportion (63%) of Palestinian men met the PA recommendations by occupation/domestic activity, compared to 39% of Palestinian women and 37% of the Israelis. No leisure time PA was reported by 42% and 39% of Palestinian and Israeli men (<it>p </it>= 0.337) and 53% and 28% of Palestinian and Israeli women (<it>p </it>< 0.0001). Palestinian women reported the lowest level of walking. Considering all domains, 26% of Palestinian women were classified as insufficiently active versus 13% of Palestinian men (<it>p </it>< 0.0001) who did not differ from the Israeli sample (14%). Middle-aged and elderly and less educated Palestinian women, and unemployed and pensioned Palestinian men were at particularly high risk of inactivity. Socio-economic indicators only partially explained the ethnic disparity.</p> <p>Conclusions</p> <p>Substantial proportions of Palestinian women, and subgroups of Palestinian men, are insufficiently active. Culturally appropriate intervention strategies are warranted, particularly for this vulnerable population.</p

Motion dazzle and camouflage as distinct anti-predator defenses.

BACKGROUND: Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms. RESULTS: Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected. CONCLUSIONS: Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are