The impedance cardiogram recorded through two electrocardiogram/defibrillator pads as a determinant of cardiac arrest during experimental studies

OBJECTIVE: Laypersons are poor at emergency pulse checks (sensitivity 84%, specificity 36%). Guidelines indicate that pulse checks should not be performed. The impedance cardiogram (dZ/dt) is used to assess stroke volume. Can a novel defibrillator-based impedance cardiogram system be used to distinguish between circulatory arrest and other collapse states?

DESIGN: Animal study.

SETTING: University research laboratory.

SUBJECTS: Twenty anesthetized, mechanically ventilated pigs, weight 50-55 kg.

INTERVENTIONS: Stroke volume was altered by right ventricular pacing (160, 210, 260, and 305 beats/min). Cardiac arrest states were then induced: ventricular fibrillation (by rapid ventricular pacing) and, after successful defibrillation, pulseless electrical activity and asystole (by high-dose intravenous pentobarbitone).

MEASUREMENTS AND MAIN RESULTS: The impedance cardiogram was recorded through electrocardiogram/defibrillator pads in standard cardiac arrest positions. Simultaneously recorded electro- and impedance cardiogram (dZ/dt) along with arterial blood pressure tracings were digitized during each pacing and cardiac arrest protocol. Five-second epochs were analyzed for sinus rhythm (20 before ventricular fibrillation, 20 after successful defibrillation), ventricular fibrillation (40), pulseless electrical activity (20), and asystole (20), in two sets of ten pigs (ten training, ten validation). Standard impedance cardiogram variables were noncontributory in cardiac arrest, so the fast Fourier transform of dZ/dt was assessed. During ventricular pacing, the peak amplitude of fast Fourier transform of dZ/dt (between 1.5 and 4.5 Hz) correlated with stroke volume (r2 = .3, p < .001). In cardiac arrest, a peak amplitude of fast Fourier transform of dZ/dt of < or = 4 dB x ohm x rms indicated no output with high sensitivity (94% training set, 86% validation set) and specificity (98% training set, 90% validation set).

CONCLUSIONS: As a powerful clinical marker of circulatory collapse, the fast Fourier transformation of dZ/dt (impedance cardiogram) has the potential to improve emergency care by laypersons using automated defibrillators.

Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity

High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are primarily due to a high prevalence of chronic hepatitis B virus infection and heavy aflatoxin exposure via groundnut consumption. We investigated genetic polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL1*2) and DNA repair (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n = 216) were compared with frequency-matched controls (n = 408) with no clinically apparent liver disease. Although the prevalence of variant genotypes was generally low, in multivariable analysis (adjusting for demographic factors, hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were significantly associated with HCC. A weak association of the HYL1*2 polymorphism with HCC was observed but did not reach statistical significance. GSTT1 was not associated with HCC. The risk for HCC with null GSTM1 was most prominent among those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and was not evident among those with less than the mean groundnut intake (OR, 0.64; 95% Cl, 0.20-2.02). Among participants who had all three suspected aflatoxin-related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a significant 15-fold increased risk of HCC was observed albeit with imprecise estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic modulation of carcinogen metabolism and DNA repair can alter susceptibility to HCC and that these effects may be modified by environmental factors.

Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants

Procedural pain in the neonatal intensive care unit triggers a cascade of physiological, behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm, who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development. The aim of this study was to examine relationships between cumulative procedural pain (number of skin-breaking procedures from birth to term, adjusted for early illness severity and overall intravenous morphine exposure), and later cognitive, motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age (CCA), and further, to evaluate the extent to which parenting factors modulate these relationships over time. Participants were N=211 infants (n=137 born preterm 32 weeks gestational age [GA] and n=74 full-term controls) followed prospectively since birth. Infants with significant neonatal brain injury (periventricular leucomalacia, grade 3 or 4 intraventricular hemorrhage) and/or major sensori-neural impairments, were excluded. Poorer cognition and motor function were associated with higher number of skin-breaking procedures, independent of early illness severity, overall intravenous morphine, and exposure to postnatal steroids. The number of skin-breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation. In general, greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months, but not at 18 months CCA, however, specific protocols for morphine administration were not evaluated. Lower parenting stress modulated effects of neonatal pain, only on cognitive outcome at 18 months.

Preferences for place of care and place of death among informal caregivers of the terminally ill

Objectives: (1) To determine informal caregivers perceptions about place of care and place of death; and (2) to identify variables associated with a home death among terminally ill individuals who received in-home support services in a publicly funded home care system. Participants and design: A total of 216 informal caregivers participated in a bereavement interview. Data collection included care recipient and informal caregiver characteristics, the use of and satisfaction with community services, and preferences about place of death. Results: Most caregivers reported that they and the care recipient had a preferred place of death (77 and 68%, respectively) with over 63% reporting home as the preferred place of death. Caregivers had a greater preference for an institutional death (14%) than care recipients (4.7%). While 30% of care recipients did not die in their preferred location, most caregivers (92%) felt, in retrospect, that where the care recipient died was the appropriate place of death. Most caregivers reported being satisfied with the care that was provided. The odds of dying at home were greater when the care recipient stated a preference for place of death (OR: 2.92; 95% CI: 1.25, 6.85), and the family physician made home visits during the care recipients last month of life (Univariate odds ratios (OR): 4.42; 95% CI: 1.46, 13.36). Discussion: The ethic of self-control and choice for the care recipient must be balanced with consideration for the well being of the informal caregiver and responsiveness of the community service system. © 2005 Edward Arnold (Publishers) Ltd.

Factors associated with home death for individuals who receive homesupportservices:A retrospective cohort study

Objectives: To determine the factors associated with a home death among older adults who received palliative care nursing home services in the home. Methods: The participants in this retrospective cohort study were 151 family caregivers of patients who had died approximately 9 months prior to the study telephone interview. The interview focused on the last year of life and covered two main areas, patient characteristics and informal caregiver characteristics. Results: Odds ratios [OR] and 95% confidence intervals [95% CI] were used to determine which of the 15 potential informal caregiver and seven patient predictor variables were associated with dying at home. Multivariate analysis revealed that the odds of dying at home were greater when the patient lived with a caregiver [OR = 7.85; 95% CI = (2.35, 26.27)], the patient stated a preference to die at home [OR= 6.51; 95% CI = (2.66,15.95)], and the family physician made home visits [OR = 4.79; 95% CI = (1.97,11.64)]. However the odds were lower for patients who had caregivers with fair to poor health status [OR = 0.22; 95% CI = (0.07, 0.65)] and for patients who used hospital palliative care beds [OR = 0.31; 95% CI = (0.12, 0.80)]. Discussion: The findings suggest that individuals who indicated a preference to die at home and resided with a healthy informal caregiver had better odds of dying at home. Home visits by a family physician were also associated with dying at home.

Fundus autofluorescence in the diagnosis of cystoid macular oedema

Aim: To determine the sensitivity and specificity of the non-invasive imaging technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular oedema (CMO), using fluorescein angiography as the reference standard. Design: Retrospective, consecutive, observational case series. Methods: Ninety-six consecutive patients with CMO suspected clinically were selected from the AF database of the Retina Unit, Ophthalmology Department, Grampian University Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO was secondary to (1) cataract extraction, (2) inherited retinopathies, (3) inflammatory eye disease or (4) idiopathic cases were included in this study. Only patients in whom AF images had been performed within 2 weeks of FFA and, when obtained following FFA, there was a minimum gap of 4 days ("washing out" period), were considered eligible for this study. A total of 34 eyes from 34 patients were eligible and were included in this study. FFA was used as the reference test to confirm the presence of CMO, and, based on fluorescein angiography (FFA), CMO was graded as either mild or florid. AF images were examined in a masked fashion for the presence or absence of CMO. The sensitivity and specificity of AF in detecting CMO were then calculated. Results: CMO was seen on AF imaging as round or oval areas at the fovea with an AF signal similar to that of background levels. At this site (fovea), the AF signal is usually reduced compared with background, due to the blockage caused by luteal pigment. The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity when compared with the reference standard FFA. Based on the FFA, there were 12 cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes). Conclusions: AF imaging can be used as a rapid, non-invasive technique in the diagnosis of CMO.

Adherence to antiepileptic medicines in children: A multiple-methods assessment involving dried blood spot sampling

Purpose: To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods.
Methods: A total of 100 children with epilepsy (=17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (=9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children.
Key Findings: The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37-15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16-11.41).
Significance: This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence. © 2013 International League Against Epilepsy.
Key Words: Adherence, Epilepsy, Dried blood spots, MARS, Depressed mood.

Effects of modified LDL and HDL on retinal pigment epithelial cells: a role in diabetic retinopathy?

Aims/hypothesis: Blood–retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown.

Methods: In human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavilyoxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate
experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5–40 µmol/l) or 4-hydroxynonenal (4-HNE, 5–80 µmol/l), with or without pretreatment with N-HDL or HOG-HDL.

Results: ApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures.

Conclusions/interpretation: In DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium.

Knowledge of UK physical activity guidelines:Implications for better targeted health promotion

Objective. The aim of this study is to investigate the correlates of knowledge of the UK physical activity (PA) guidelines.

Method. A Northern Ireland-wide population survey (2010/2011) of 4653 adults provided cross-sectional data on PA, knowledge of guidelines and socio demographic characteristics. Multinomial logistic regression was used to investigate the associations between knowledge and socio-demographic characteristics (Model 1); and modifiable health behaviours (Model 2).

Results. Results showed that 47% of respondents were unaware of PA guidelines. Males who had a lower level of education (OR 5.91; 95% CI 1.67, 20.94), lived in more deprived areas (OR 4.80; 95% CI 1.87, 12.30), low income (OR 2.36; 95% CI 1.63, 3.41) and did no PA (OR 2.74; 95% CI 1.31, 5.76) were more likely to be unaware of the guidelines. Females who were younger (OR 1.03; 95% CI 1.02, 1.05) and reported poor health (OR 2.71; 95% CI 1.61, 4.58) were more likely to be unaware of the guidelines.

Conclusion. There is a lack of awareness about the levels of PA needed to promote health. An understanding of the characteristics of those who are unaware of the guidelines has important implications for the design of targeted, effective health promotion.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.

Robot and insect navigation by polarized skylight

A study of a large number of published experiments on the behaviour of insects navigating by skylight has led to the design of a system for navigation in lightly clouded skies, suitable for a robot or drone. The design is based on the measurement of the directions in the sky at which the polarization angle, i.e. the angle χ between the polarized E-vector and the meridian, equals ±π/4 or ±(π/4 + π/3) or ±(π/4 - π/3). For any one of these three options, at any given elevation, there are usually 4 such directions and these directions can give the azimuth of the sun accurately in a few short steps, as an insect can do. A simulation shows that this compass is accurate as well as simple and well suited for an insect or robot. A major advantage of this design is that it is close to being invariant to variable cloud cover. Also if at least two of these 12 directions are observed the solar azimuth can still be found by a robot, and possibly by an insect.

Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions

Ischaemic strokes evoke blood-brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen-glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions. Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection.

Remediation of oily wastewater from an interceptor tank using a novel photocatalytic drum reactor

A novel photocatalytic reactor has been developed to remediate oily wastewaters. In the first instance degradation rates of model organic compounds, methylene blue (MB) and 4-c hlorophenol (4-CP) were determined. The experimental set-up investigated a 1:10 w/v catalyst to organic solution volume, 30 g catalyst, 300 mls MB (10 μM) or 4-CP (100 μM). The catalyst investigated was a pellet catalyst to improve separation of the remediated volume from the catalyst following treatment. MB concentration decreased by 93% after 15 mins irradiation whilst 4-CP concentration decreased by 94% following 90 mins irradiation. Oily waste water (OWW) from an interceptor tank typically containing diesel oils was obtained from Sureclean, an environmental clean-up company. The OWW was treated using the same conditions as MB and 4-CP, the model organic compounds. Levels of total organic carbon (TOC) and total petroleum hydrocarbon (TPH) were used to monitor the efficacy of the photocatalytic reactor. TOC reduced by 45% following two 90 mins treatment cycles. TPH reduced by 45% following 90 mins irradiation and by a further 25% during a second stage of treatment. This reactor can be used as a polishing technique assembled within a wastewater treatment plant. Allowing for more than one pass through the reactor improves its efficiency. 

Mechanistic studies of the photocatalytic oxidation of microcystin-LR: An investigation of byproducts of the decomposition process

Microcystins (cyclic heptapeptides) are produced by a number of freshwater cyanobacteria and cause concern in potable water supplies due to their acute and chronic toxicity. The present study reports the structural characterization of the degradation products of the photocatalytic oxidation of microcystin-LR, so aiding the mechanistic understanding of this process. TiO₂ photocatalysis is a promising technology for removal of these toxins from drinking water. However, before it can be adopted in any practical application it is necessary to have a sufficient knowledge of degradation byproducts and their potential toxicity. Liquid chromatography-mass spectrometry analysis demonstrated that the major destruction pathway of microcystin appears to be initiated via three mechanisms: UV irradiation, hydroxyl radical attack, and oxidation. UV irradiation caused geometrical isomerization of microcystin converting the (4E), (6E) of the Adda configuration to (4E), 6(Z) or 4(Z), 6(E). Hydroxyl radical attack on the conjugated diene structure of Adda moiety produced dihyroxylated products. Further oxidation cleaved the hydroxylated 4-5 and/or 6-7 bond of Adda to form aldehyde or ketone peptide residues, which then were oxidized into the corresponding carboxylic acids. Photocatalysis also hydrolyzed the peptide bond on the ring structure of microcystin to form linear structures although this appeared to be a minor pathway.

In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription

BACKGROUND: LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB), synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only.

RESULTS: We report that disruption of luxS renders H. pylori non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp (other genes in the cysteine provision pathway) does not, implying that the lost phenotype is not due to disrupted cysteine provision. The motility defect of the DeltaluxSHp mutant was complemented genetically by luxSHp and also by addition of in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor of AI-2). In contrast, exogenously added cysteine could not restore motility to the DeltaluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic effect of LuxS was important. Microscopy showed reduced number and length of flagella in the DeltaluxSHp mutant. Immunoblotting identified decreased levels of FlaA and FlgE but not FlaB in the DeltaluxSHp mutant, and RT-PCR showed that the expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced. Addition of DPD but not cysteine to the DeltaluxSHp mutant restored flagellar gene transcription, and the number and length of flagella.

CONCLUSIONS: Our data show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative role in regulation of motility by modulating flagellar transcripts and flagellar biosynthesis through production of the signalling molecule AI-2.