bluuebunny/crossref_metadata_2025 huggingface dataset:
PS55 The Use Of A Wealth Index Within An Impoverished Community: A Cohort Study In Kwazulu-Natal, South Africa
Authors: Davidson LL , Kauchali S , Chhagan MK , Bah F , Uwemedimo OOT , Craib MH , McKeague I
Published: September 2012

Background

An index of wealth is widely used in national surveys to create economic profiles. We constructed such an index within a population-based cohort study of 1,788 preschool children and their primary caregivers living in five isiZulu tribal areas of KwaZulu-Natal, South Africa, an extremely poor area which remains at the epi-center of the South African HIV/AIDS epidemic.

Methods

Study Design: Information on household assets, employment, household structure was obtained by door-to-door survey alongside a screen for child disability in developing countries. All children were invited to a structured medical and psychological assessment for disability and HIV status of child and primary caregiver. Wealth Index: A household asset index developed within our study population used many items identical to those in WHO DHS surveys, employing a principal components approach. Asset indicators were grouped into 3 categories: land ownership, ownership of consumer goods, and characteristics of household dwelling (building material, water sources, toilet facility, energy source, etc.). Factor analysis was performed: variables with zero variances and all variables with prevalence less than 2% were removed. The first component explained 16% of the variance and a KMO of 0.532. We ranked the factor scores on the first component in ascending order, standardized to a range of 0 to 4, and grouped into tertiles (1=lowest third, 2=middle third, 3=top third).

Results

The wealth index gave information about study participation: Of 1788 children screened, children from households in the poorest third were significantly more likely to be brought to the assessment: 91% compared to 83 and 89 % in the middle and top third respectively. Significant differences in the wealth index were found between the five areas in the sample. With regard to caregiver responses about child disability, those in the poorest third were most likely to report that their child had a disability (43% compared to 46 and 49% - significant on test for trend). Though doctors found a lower rate of disability than reported by parents, there was no difference in disability or false positives rate by wealth index tertile. HIV seropositivity of caregiver varied by tertile (30.3%, 28.5% and 21.8 % in poorest, middle and least poor) but not that of children.

Conclusion

Even within extremely deprived areas in a low or middle income country, a wealth index can assess comparative risk among groups suffering more or less material disadvantage and also provide important information in assessing possibility of selection bias in the findings.
DYNAMICS OF FIRST ORDER EQUATIONS WITH NONLINEAR DELAYED FEEDBACK
Authors: KASCHENKO D. , KASCHENKO S. , SCHWARZ W.
Published: September 2012

In this paper, we have studied an important class of first order differential equations with nonlinear delayed feedback. The nonlocal dynamics of such equations was investigated by analytical and numeric–analytical methods. An approach based on asymptotic analysis made it possible to study attractors consisting of impulse type solutions. We obtained some numerical characteristics of irregular oscillations and studied their dependence on the delay.
HYPERBOLIC-LIKE PROPERTIES OF POPP'S ATTRACTOR
Authors: STEFAŃSKI ANDRZEJ , WOJEWODA JERZY , CHUDZIK AGNIESZKA , KAPITANIAK TOMASZ
Published: September 2012

We compare typical properties of the hyperbolic and quasi-hyperbolic attractors with the properties of the particular attractor observed in the classical dry friction oscillator excited by external harmonic drive [Popp & Stelter, 1990a; Hinrichs et al., 1998; Oestreich et al., 1996]. Our analysis shows that the main common feature of these attractors is their structural stability (in spite of their chaotic nature), which is manifested by a low sensitivity of system dynamics and the structure of the phase-space for changes of parameters in differential equations.
PIECEWISE SMOOTH REVERSIBLE DYNAMICAL SYSTEMS AT A TWO-FOLD SINGULARITY
Authors: JACQUEMARD A. , TEIXEIRA M. A. , TONON D. J.
Published: September 2012

This paper focuses on the existence of closed orbits around a two-fold singularity of 3D discontinuous systems of the Filippov type in the presence of symmetries.
NONLINEAR BEHAVIORS OF GEAR SHIFTING DIGITAL PHASE LOCKED LOOPS
Authors: CHEN XI , LING BINGO WING-KUEN , SUN LI-MIN
Published: September 2012

Applying gear shifting algorithms to the implementation of Phase Locked Loops (PLLs) can significantly improve their performances. However, the behaviors of gear shifting digital PLLs (GSDPLLs) have not been fully studied due to the existence of newly adaptive control parameters. These parameters play a very important role in the design of GSDPLLs. In this paper, various nonlinear behaviors of GSDPLLs including the steady state periodic behaviors, divergent behaviors and chaotic behaviors, are studied. In particular, the effects of the initial conditions of GSDPLLs on their dynamical behaviors are investigated. The obtained results are useful for the design of GSDPLLs. Numerical simulation results are presented for illustrations.
CORRELATION OF KINETIC MOMENT OF INERTIA WITH POWER FORMULA INDEX
Authors: KUMAR RAJESH , KATOCH VIKAS , SHARMA S. , GUPTA J. B.
Published: September 2012

The level energies of ground band of even Z, even N nuclei may be reproduced well with good accuracy by using the power index formula E = aIb. In an earlier study of the dependence of the kinetic moment of inertia (MoI) J(1) on spin I, a possible correlation of the MoI J(1) with power index "b" was suggested. Here we illustrate that the slope of the kinetic MoI versus spin I corresponds to the magnitude of the index "b" for several isotopes in the A = 100–150 region. The validity of the formula is illustrated for light nuclei in A = 100 region and its use for studying shape phase transition at N = 60.
p-TYPE NITROGEN-DOPED ZnO MICRORODS PREPARATION BY SPRAY PYROLYSIS
Authors: ZAHEDI F. , DARIANI R. S. , ROZATI S. M.
Published: September 2012

Nitrogen doped ZnO films with different N/Zn atomic ratio have been prepared by spray pyrolysis technique on glass substrate at 500°C. N/Zn atomic ratio has been selected 0, 0.5, 1, 2 and 3. The effect of N/Zn ratio on structural, optical and electrical properties has been investigated. Hall effect measurement studies show that the conductivity type of the films is affected by N/Zn ratio. The conductivity type of films changes from n for N/Zn = 0 and 0.5 to p for N/Zn = 1 and 2. Further increasing in N/Zn to 3 again led to n-type conductivity. p-type ZnO:N microrods film prepared with N/Zn = 1 has highest carrier concentration (1.36 × 1016 cm-3) and lowest resistivity (628 Ω.cm). All films are polycrystalline with hexagonal wurtzite structure. (002) plane is preferential orientation for all films. Surface morphology changes from rods to grains by increasing in N/Zn ratio. Optical transmission of the films increases with increasing in N/Zn ratio. Photoluminescence spectra at room temperature show the ultraviolet emission and two visible emissions at 440 nm and 520 nm. X-ray photoelectron spectroscopy analysis confirms the incorporation of nitrogen in ZnO:N film with N/Zn = 1 .
APPROXIMATION OF EMPOWERMENT IN THE CONTINUOUS DOMAIN
Authors: SALGE CHRISTOPH , GLACKIN CORNELIUS , POLANI DANIEL
Published: September 2012

The empowerment formalism offers a goal-independent utility function fully derived from an agent's embodiment. It produces intrinsic motivations which can be used to generate self-organizing behaviors in agents. One obstacle to the application of empowerment in more demanding (esp. continuous) domains is that previous ways of calculating empowerment have been very time consuming and only provided a proof-of-concept. In this paper we present a new approach to efficiently approximate empowerment as a parallel, linear, Gaussian channel capacity problem. We use pendulum balancing to demonstrate this new method, and compare it to earlier approximation methods.
Responses of Algal Cells to Engineered Nanoparticles Measured as Algal Cell Population, Chlorophyll a, and Lipid Peroxidation: Effect of Particle Size and Type
Authors: Metzler D. M. , Erdem A. , Tseng Y. H. , Huang C. P.
Published: September 2012

This paper investigated toxicity of three engineered nanoparticles (ENP), namely, Al2O3, SiO2, and TiO2to the unicellular green algae, exemplified byPseudokirchneriella subcapitatawith an emphasis on particle size. The changes in pH, cell counts, chlorophyll a, and lipid peroxidation were used to measure the responses of the algal species to ENP. The most toxic particle size was TiO2at 42 nm with an EC20 of 5.2 mg/L and Al2O3at 14–18 nm with an EC20 of 5.1 mg/L. SiO2was the least toxic with an EC20 of 318 mg/L. Toxicity was positively related to the surface charge of both ENP and algae. The chlorophyll content of the algal cells was influenced by the presence of ENP, which resulted in limited light and availability of nutrients due to increase in turbidity and nutrient adsorption onto the ENP surface, separately. Lipid peroxidation was attributed to reactive oxygen species (ROS). Fast reaction between algal cells and ROS due to direct contact between TiO2and algal cells is an important factor for lipid peroxidation.
The Challenges of Dialysis in Systemic Sclerosis: Between the Devil and the Deep Blue Sea?
Authors: Brown N. , Summers A. , Venning M. C. , Bruce I. N.
Published: September 2012

We present the case of a patient with systemic sclerosis (SSc) and end stage renal disease (ESRD) who experienced complications of both peritoneal and haemodialysis. We review previously reported outcomes of patients with systemic sclerosis on dialysis and discuss potential shared mechanisms in both the disease pathogenesis and dialysis-related complications, particularly with regards to encapsulating peritoneal sclerosis (EPS).
Effectiveness and Cost-Effectiveness of Dialectical Behaviour Therapy for Self-Harming Patients with Personality Disorder: A Pragmatic Randomised Controlled Trial
Authors: Priebe Stefan , Bhatti Nyla , Barnicot Kirsten , Bremner Stephen , Gaglia Amy , Katsakou Christina , Molosankwe Iris , McCrone Paul , Zinkler Martin
Published: September 2012

Background: A primary goal of dialectical behaviour therapy (DBT) is to reduce self-harm, but findings from empirical studies are inconclusive. The aim of this study was to assess the effectiveness and cost-effectiveness of DBT in reducing self-harm in patients with personality disorder. Methods: Participants with a personality disorder and at least 5 days of self-harm in the previous year were randomised to receive 12 months of either DBT or treatment as usual (TAU). The primary outcome was the frequency of days with self-harm; secondary outcomes included borderline personality disorder symptoms, general psychiatric symptoms, subjective quality of life, and costs of care. Results: Forty patients each were randomised to DBT and TAU. In an intention-to-treat analysis, there was a statistically significant treatment by time interaction for self-harm (incidence rate ratio 0.91, 95% CI 0.89–0.92, p < 0.001). For every 2 months spent in DBT, the risk of self-harm decreased by 9% relative to TAU. There was no evidence of differences on any secondary outcomes. The economic analysis revealed a total cost of a mean of 5,685 GBP (6,786 EUR) in DBT compared to a mean of 3,754 GBP (4,481 EUR) in TAU, but the difference was not significant (95% CI –603 to 4,599 GBP). Forty-eight per cent of patients completed DBT. They had a greater reduction in self-harm compared to dropouts (incidence rate ratio 0.78, 95% CI 0.76–0.80, p < 0.001). Conclusions: DBT can be effective in reducing self-harm in patients with personality disorder, possibly incurring higher total treatment costs. The effect is stronger in those who complete treatment. Future research should explore how to improve treatment adherence.
Cognitive Therapy versus Fluvoxamine as a Second-Step Treatment in Obsessive-Compulsive Disorder Nonresponsive to First-Step Behavior Therapy
Authors: van Balkom Anton J.L.M. , Emmelkamp Paul M.G. , Eikelenboom Merijn , Hoogendoorn Adriaan W. , Smit Johannes H. , van Oppen Patricia
Published: September 2012

Background: To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP). Methods: A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an ‘as randomized basis’ and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed. Results: Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ2(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed. Conclusions: OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably.
Increased Serum Heat Shock Protein 27 Antibody Titers and Prooxidant-Antioxidant Balance in Patients with Beta-Thalassemia Major
Authors: Saber Hamidreza , Banihashem Abdollah , Saber Hamidreza , Tavallaie Shima , Mirhosseini Naghmeh , Ghayour-Mobarhan Majid , Ferns Gordon A.A.
Published: September 2012

Objective: Determination of the serum heat shock protein 27 (Hsp27) antibody titers and prooxidant-antioxidant balance (PAB) in patients with thalassemia as markers of cell and oxidative stress, respectively. Methods: Serum PAB and anti-Hsp27 antibody titers were measured in 140 patients with thalassemia major and 140 sex- and age-matched healthy volunteers. Results: A significantly higher serum PAB value was observed in patients in comparison to controls. In the patient group, anti-Hsp27 antibody titers were significantly higher than for the control group (p < 0.001). We found a weak negative correlation between anti-Hsp27 antibody concentrations and the PAB (p = 0.03), but these values were not correlated with serum superoxide dismutase activity in the thalassemic patients. Conclusions: Increased levels of serum PAB and Hsp27 antibodies may be involved in the pathological consequences of β-thalassemia major and may contribute to the development of endothelial injury.
Secreted Factors from Human Mast Cells Trigger Inflammatory Cytokine Production by Human Airway Smooth Muscle Cells
Authors: Xia Y.C. , Harris T. , Stewart A.G. , Mackay G.A.
Published: September 2012

Background: A notable feature of allergic asthma is the infiltration of mast cells into smooth muscle in the human airway. Thus, mast cells and human airway smooth muscle (hASM) cells are likely to exhibit mutual functional modulation via direct cell-cell contact or through released factors. This study examined mast cell modulation of hASM cell cytokine release. Methods: The mast cell line HMCα was used to model mast cell function. hASM cells were either co-cultured directly with resting or IgE/antigen-stimulated HMCα cells or treated with HMCα-conditioned media to examine the impact on cytokine release. The activation pathways triggered in hASM cells by the mast cell-derived factors were examined through the use of selective inhibitors and by Western blotting. Results: HMCα cells, or their conditioned media, induced the expression of cytokines (IL-8 and IL-6) by hASM cells at both the mRNA and the protein level. Cytokine expression in hASM cells was greatly amplified when HMCα cells were IgE/antigen-activated. The effects of the conditioned media were not mediated by the chemokines MCP-1 and MIP-1α or by exosomes. While the mast cell-derived factor(s) increased p38MAPK phosphorylation in hASM cells, cytokine production was not inhibited by the p38MAPK inhibitor SB203580. hASM cell production of IL-8 induced by HMCα condition media but not IL-6 was, however, attenuated by the Src tyrosine kinase inhibitor PP2. Conclusions: Our study shows that the release of soluble mediators by activated mast cells can stimulate hASM cells to elicit production of proinflammatory cytokines that may then exacerbate airway inflammation in asthma.
Osteoprotegerin Predicts Long-Term Outcome in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention
Authors: Pedersen Sune , Mogelvang Rasmus , Bjerre Mette , Frystyk Jan , Flyvbjerg Allan , Galatius Soren , Sørensen Tor Biering , Iversen Allan , Hvelplund Anders , Jensen Jan S.
Published: September 2012

Background: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22–33). Results: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03–1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00–1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18–1.90; p = 0.001). Conclusion: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome.
Fractional Anisotropy in Three Variants of Primary Progressive Aphasia
Authors: Magnin Eloi , Cattin Françoise , Vandel Pierre , Galmiche Jean , Moulin Thierry , Rumbach Lucien
Published: September 2012

Objective: Our aim was to report diffusion tensor imaging (DTI) patterns in three patients, each with a different primary progressive aphasia (PPA) variant. Design: One agrammatic PPA, one semantic PPA, and one logopenic PPA subject underwent a magnetic resonance imaging examination including DTI sequences. The fractional anisotropy (FA) value was calculated in regions of interest (ROIs) involved in these three variants (perisylvian region, temporal pole, and parietotemporal junction) for each patient. Left-right FA ratios in each ROI were compared between PPA subjects and a group of three amnestic mild cognitive impairment patients with a cerebrospinal fluid biomarker profile of the Alzheimer type. Results: The FA values were lower in the left hemisphere (p = 0.03). The lowest FA values were observed in the left perisylvian region for the non-fluent/agrammatic subtype PPA patient, in the left anterior temporal lobe for the semantic subtype PPA patient, and in the left parietotemporal junction for the logopenic patient (p = 0.028). The left-right FA ratio in these specific ROIs for each PPA variant was significantly lower than in the amnestic mild cognitive impairment group (p = 0.009). Conclusion: DTI patterns could be an effective new tool for diagnosing PPA and classifying the three variants.
Distal Hyperintense Vessels on Flair: A Prognostic Indicator of Acute Ischemic Stroke
Authors: Huang Xianjun , Liu Wenhua , Zhu Wusheng , Ni Guanzhong , Sun Wen , Ma Minmin , Zhou Zhiming , Wang Qizhang , Xu Gelin , Liu Xinfeng
Published: September 2012

Background: Hyperintense vessels (HVs) on fluid-attenuated inversion recovery (FLAIR) are frequently observed in acute ischemic stroke (AIS). The presence of HVs represents altered blood flow from collaterals distal to arterial occlusion or stenosis. This study aimed to evaluate the prognostic value of HVs in AIS. Methods: Fifty-four consecutive patients with acute middle cerebral artery occlusion were enrolled in the study. The location and extent of the HVs was determined by FLAIR. Clinical data were obtained and compared between patients with different grades of HVs. Additionally, the relationship between distal HVs and leptomeningeal collaterals (LMCs) was assessed using angiography. Results: HVs were observed in 41 (75.9%) of the 54 patients enrolled. The initial NIHSS score was lower (p < 0.001) and the infarction volume was smaller (p < 0.001) in patients with distal HVs. Adjusting of other factors, regression analysis revealed that distal HVs are an independent predictor of a favorable outcome at 90 days (p = 0.006; OR 0.049; 95% CI 0.006–0.420). Furthermore, the presence of distal HVs was correlated with the presence of LMCs. Conclusion: Distal HVs may be a marker for LMCs and act as a predictor of a favorable clinical outcome for patients with AIS.
Microvascular Effect of Intracoronary Eptifibatide in Acute Myocardial Infarction
Authors: Iancu Adrian , Ober Camelia , Bondor Cosmina Ioana , Cadiş Horaţiu
Published: September 2012

Objectives: In this prospective, randomized trial in patients with acute myocardial infarction (AMI) admitted for primary percutaneous coronary intervention (PPCI), loaded with 600 mg clopidogrel, we hypothesized that eptifibatide administered downstream of the coronary occlusion leads to a lower degree of microvascular obstruction compared with no additional eptifibatide. Methods: Fifty patients with AMI, loaded with 600 mg of clopidogrel at the first hospital contact, with occlusion of the left anterior descending artery (LAD), were randomized to an eptifibatide group (EG) or a control group (CG). In both groups, stenting was performed after thrombus aspiration. Microvascular reperfusion was assessed by angiography, electrocardiography, and transthoracic Doppler ultrasonography of the LAD. Results: TIMI myocardial perfusion grade 2–3 was not different between the EG (72%) and the CG (84%) (p = 0.31). ST segment resolution >70% was similarly detected in both groups (32 vs. 40%; p = 0.56). The mean diastolic deceleration time did not differ significantly between the CG (856.36 ± 397.88 ms) and the EG (935.72 ± 252.22 ms) (p = 0.41). Multivariate logistic regression revealed no significant influence of the treatment with eptifibatide on ST segment resolution (OR 0.47; 95% CI 0.11–2.10, p = 0.32), TIMI myocardial perfusion (OR 0.52; 95% CI 0.10–2.59, p = 0.42), and diastolic deceleration time (OR 0.21; 95% CI 0.03–1.51, p = 0.12). Conclusions: In AMI patients loaded with 600 mg of clopidogrel undergoing PPCI, intracoronary administration of eptifibatide does not clearly improve microvascular obstruction.
Association between Arterial Elasticity Indices and Coronary Artery Calcium in a Healthy Multi-Ethnic Cohort
Authors: Panaich Sidakpal S. , Zalawadiya Sandip K. , Veeranna Vikas , Afonso Luis
Published: September 2012

Objectives: Reduced arterial elasticity is a risk factor for coronary artery disease. Our main objective was to evaluate the association between large arterial elasticity (LAE) and small arterial elasticity (SAE) with subclinical atherosclerosis as reflected by the coronary artery calcium score (CACS). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) includes a multi-ethnic, population-based cohort (n = 6,814), aged 45–84 years, free from clinical cardiovascular disease. We undertook a post hoc analysis of the NHLBI limited access data set of MESA subjects (n = 6,278) to evaluate the association between LAE and SAE with CACS [divided in to 4 categories: none (reference), 1–99, 100–299, and ≥300] using multivariable adjusted logistic regression analysis. Results: After adjustments for age, sex, systolic blood pressure, anti-hypertensive medications use, race, smoking, diabetes, high-density lipoprotein and total cholesterol, and high-sensitivity C-reactive protein, both LAE [adjusted odds ratio (aOR) 0.65; 95% CI 0.49–0.87 for CACS ≥300] and SAE (aOR 0.68, 95% CI 0.56–0.83 for CACS ≥300) were significantly (p < 0.001 for both) associated with a higher CACS. Conclusion: Both LAE and SAE, independent of traditional risk factors and inflammation, are associated with subclinical coronary atherosclerosis.
High Prevalence of Gastroesophageal Reflux Symptoms in Patients with Non-Alcoholic Fatty Liver Disease Associated with Serum Levels of Triglyceride and Cholesterol but Not Simple Visceral Obesity
Authors: Fujikawa Yoshiko , Tominaga Kazunari , Fujii Hideki , Machida Hirohisa , Okazaki Hirotoshi , Yamagami Hirokazu , Tanigawa Tetsuya , Watanabe Kenji , Watanabe Toshio , Fujiwara Yasuhiro , Matsuura Toshifumi , Kawada Norifumi , Arakawa Tetsuo
Published: September 2012

Background/Aims: Visceral obesity is commonly involved in the pathogenesis of gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, other characteristic factors different from visceral obesity are associated with the pathogenesis of NAFLD. We investigated the prevalence of GERD symptoms in patients with NAFLD and its associated risk factors. Methods: NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD. Results: GERD symptom score and its prevalence rate were higher in the NAFLD group (7.4 ± 0.7, 37%) than those seen in the control groups (4.5 ± 0.4, 20%), which was independent of sex, age, and body mass index (BMI). GERD symptoms were correlated with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r = 0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms of the NAFLD group were significantly severer in the higher group of T-CHO and TG levels than those in the lower group. Multivariate analysis proved that risk factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31–11.9) and T-CHO (OR 3.39, 95% CI 1.11–10.3). Conclusion: The severity and prevalence of GERD symptoms in patients with NAFLD were high, which was associated with serum levels of TG and T-CHO but not BMI.
Combined Rifampicin and Ursodeoxycholic Acid Treatment Does Not Amplify Rifampicin Effects on Hepatic Detoxification and Transport Systems in Humans
Authors: Marschall Hanns-Ulrich , Wagner Martin , Zollner Gernot , Fickert Peter , Silbert Dagmar , Gustafsson Ulf , Sahlin Staffan , Trauner Michael
Published: September 2012

Background: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) were found to stimulate different but complementary hepatobiliary detoxification pathways in gallstone patients. Aim: To study whether single drug effects are sustained or even enhanced by combination of both drugs and whether possible effects are mediated by circulating fibroblast growth factor 19 (FGF19), which has recently been identified as a master regulator of bile acid biosynthesis. Methods: 20 patients scheduled for laparoscopic cholecystectomy were randomized to a combination of UDCA (1 g/day during 3 weeks before surgery) and RIFA (600 mg/day during 1 week before surgery), or no treatment. Routine biochemistry, lipids, bile acid synthesis (7α-hydroxy-4-cholesten-3-one, C-4) and FGF19 were measured in serum. Bile acids were analyzed in serum and bile. A wedge liver biopsy was taken for determination of expression of hepatobiliary ABC transporters on mRNA and protein levels and of enzymes and regulatory transcription factors involved in the metabolism of biliary compounds on mRNA levels. Results: Combination treatment with both RIFA and UDCA significantly stimulated bile acid and bilirubin detoxification (CYP3A4, p < 0.001), conjugation (UGT1A1, p < 0.001) and elimination (MRP2, p < 0.05), as well as bile acid synthesis (p < 0.05), as compared to untreated controls. Notably, serum FGF19 levels in RIFA- and UDCA-treated patients did not differ from controls. Conclusion: Combined treatment with RIFA and UDCA preserves the previously observed beneficial effects of single treatment with RIFA, including stimulation of bile acid synthesis. Most notably, the latter effect in humans is not mediated by FGF19.
Elevated Plasma Cytokines in Japanese Patients with Eosinophilic Esophagitis and Gastroenteritis
Authors: Kinoshita Yoshikazu , Furuta Kenji , Ishimura Norihisa , Ishihara Shunji
Published: September 2012

Background/Aim: The role of Th2-type cytokines in development of eosinophilic esophagitis (EoE) has been largely revealed, whereas research on the pathogenesis of eosinophilic gastroenteritis (EGE) has not been widely performed. We investigated the possible involvement of Th2-type cytokines in EGE by measuring plasma cytokine concentrations in patients with EGE as well as those with EoE. Methods: 18 patients with EoE, 18 with EGE, and 30 normal volunteers were enrolled in the study. Plasma concentrations of five cytokines (thymic stromal lymphopoietin, IL-5, IL-13, IL-15, and eotaxin-3) were measured using Milliplex® assays. Clinical characteristics of the patients and plasma cytokine levels were then compared. Results: Higher proportions of patients with EoE and those with EGE showed elevated plasma concentrations of IL-5 and IL-15 as compared to the normal controls. There was also a positive correlation between IL-5 and IL-15, and also with blood eosinophil count. The plasma concentrations of these cytokines tended to be higher in cases with EGE than in those with EoE, though there were overlaps in cytokine levels among the patients and controls. Conclusion: Similar increases in plasma IL-5 and IL-15 were observed in patients with EoE and those with EGE.
Perforation and Postoperative Bleeding of Endoscopic Submucosal Dissection in Gastric Tumors: Analysis of 1,190 Lesions in Low- and High-Volume Centers in Saga, Japan
Authors: Miyahara Koichi , Iwakiri Ryuichi , Shimoda Ryo , Sakata Yasuhisa , Fujise Takehiro , Shiraishi Ryosuke , Yamaguchi Kanako , Watanabe Akira , Yamaguchi Daisuke , Higuchi Toru , Tominaga Naoyuki , Ogata Shinichi , Tsuruoka Nanae , Noda Takahiro , Hidaka Hidenori , Mannen Kotaro , Endo Hiroyoshi , Yamanouchi Kohei , Yamazato Tetsuro , Sakata Hiroyuki , Fujimoto Kazuma
Published: September 2012

Background: This retrospective study aimed to determine risk factors associated with serious complications of endoscopic submucosal dissection of gastric tumors in multicenters compared between high- and low-volume centers. Methods: Between 2001 and 2010, gastric endoscopic submucosal dissection was performed in 1,190 lesions of 1,082 patients in five hospitals in Saga, three high-volume and two low-volume centers. Risk factors for serious complications were evaluated. Patients’ background characteristics were evaluated, including anticoagulants use and underlying diseases. Results: Postoperative bleeding was detected in 75 patients (6.9%), and perforation was detected in 40 patients (3.7%). Most postoperative bleeding and perforation cases were recovered with endoscopic procedures, although one case of each complication was treated by emergency surgery. Multivariate analysis indicated that risk factors for perforation were tumor location, massive submucusal invasion, endoscopists’ experience of 100–149 cases and hypertension, and that risk factors for postoperative bleeding were tumor location, resected tumor size, and scar lesion. The serious complications were not different between high- and low-volume centers. Conclusions: The present study indicated that risk factors for perforation during endoscopic submucosal dissection were tumor, endoscopist and patient related, although risk factors for postoperative bleeding were tumor related. There was no difference in complications between high- and low-volume centers.
Prediction of Esophageal Variceal Bleeding in B-Viral Liver Cirrhosis Using the P2/MS Noninvasive Index Based on Complete Blood Counts
Authors: Kim Beom Kyung , Ahn Sang Hoon , Han Kwang-Hyub , Park Jun Yong , Han Min Seok , Jo Jung Hyun , Kim Ja Kyung , Lee Kwan Sik , Chon Chae Yoon , Kim Do Young
Published: September 2012

Background/Aim: Periodic endoscopy for esophageal varices (EVs) and prophylactic treatment of high-risk EVs, i.e. medium/large EVs, small EVs with the red-color sign or decompensation, are recommended in cirrhotic patients. We assessed the cumulative risks for future EV bleeding using the following simple P2/MS index: (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)]. Methods: We enrolled 475 consecutive B-viral cirrhosis patients for 4 years, none of whom experienced EV bleeding. All underwent laboratory work-ups, endoscopy and ultrasonography. Those with EV bleeding took a nonselective β-blocker as prophylaxis. The major endpoint was the first occurrence of EV bleeding, analyzed using the Kaplan-Meier and Cox regression methods. Results: Among patients with EV bleeding (n = 131), 25 experienced their first EV bleeding during follow-up. To differentiate the risk for EV bleeding, we divided them into two subgroups according to their P2/MS value (subgroup 1: P2/MS ≥9 and subgroup 2: P2/MS <9). The risk was significantly higher in subgroup 2 (p = 0.029). From multivariate analysis, a lower P2/MS (p = 0.040) remained a significant predictor for EV bleeding along with large varix size (p = 0.015), red-color sign (p = 0.041) and Child-Pugh classification B/C (p = 0.001). In subgroup 1, the risk for EV bleeding was similar to that of patients with low-risk EVs (p = 0.164). Conclusions: The P2/MS is a reliable predictor for the risk of EV bleeding among patients with EV bleeding. According to risk stratification, different prophylactic treatments should be considered for the subgroup with a P2/MS <9.
Bacterial Stimulation of the TLR-MyD88 Pathway Modulates the Homeostatic Expression of Ileal Paneth Cell α-Defensins
Authors: Menendez A. , Willing B.P. , Montero M. , Wlodarska M. , So C.C. , Bhinder G. , Vallance B.A. , Finlay B.B.
Published: September 2012

Paneth cell α-defensins are antimicrobial peptides involved in the control of the intestinal microbiota and immunological homeostasis. In mice, they are encoded by multiple, highly homologous genes (Defa). The transcriptional activity of ileal Defa genes was studied in response to pharmacological and genetic perturbations of the intestinal environment of C57BL/6 mice. Defa gene transcription was sensitive to oral antibiotic administration suggesting that commensal microbes regulate Defa expression. Ileal microbiota analysis showed that decreased transcription of Defa genes correlated with depletion of Lactobacillus. Defa expression was partially restored in vivo by lactobacillus administration to antibiotic-treated mice. Defa transcripts were less abundant in ex vivo, microbiota-free intestinal explants but recovered after explant exposure to UV-killed bacteria, Toll-like receptor (TLR)-2 or TLR4 agonists. Genetic deficiency of several TLRs or MyD88 led to dramatic drops in Defa transcription in vivo. These results show that Paneth cell Defa genes are regulated by commensal bacteria through TLR-MyD88 signaling and provide a further understanding of the dysregulation of intestinal homeostasis that occurs as a result of imbalances in the populations of commensal bacteria.
Effectiveness of Varenicline as an Aid to Smoking Cessation in Primary Care: An Observational Study
Authors: Andreas Stefan , Chenot Jean-François , Diebold Ruth , Peachey Sarah , Mann Karl
Published: September 2012

Aims: Although varenicline is commonly prescribed in primary care, information on smoking-related comorbidities and the effectiveness of varenicline in this context in Germany is scarce. This study assessed the efficacy and safety of varenicline in a large sample of patients seeking smoking cessation treatment through their general practitioners. The frequency of comorbidities was also evaluated. Methods: This was a 12-week, prospective, observational, non-comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were evaluated by verbal reporting using the nicotine use inventory. Results: Overall, 1,391 subjects were enrolled; 1,177 received study medication and were evaluated for effectiveness and safety. At the end of the study, 71.1% (95% confidence interval 68.5–73.7) of subjects were abstinent. There were a total of 205 all-causality adverse events; 2.2% were classified as serious or severe. There were no fatal adverse events. At inclusion, 66.7% of participants had at least 1 concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%), hypertension (29.6%) and depression (10.4%) being the most commonly reported. Conclusion: These real-world data indicate that varenicline is an effective and well-tolerated smoking cessation treatment when used in the primary care setting including patients with smoking-related comorbidities.
Sepsis: Going to the Heart of the Matter
Authors: Celes Mara R.N. , Prado Cibele M. , Rossi Marcos A.
Published: September 2012

Although myocardial depression is the predominant cause of death in severe sepsis/septic shock, it remains disputed whether the functional changes are a consequence of structural alterations. If we look at myocardial dysfunction from the perspective of a critically ill patient, there are a few questions to be asked: What causes myocardial dysfunction? What is the pathophysiology of cardiac dysfunction and death? Is there something that could be done to prevent the outcome? Each of these questions is interrelated and the answers will be more easily addressed if we continue to understand the basic mechanisms that are implicated. The principal mechanisms proposed for the pathogenesis of myocardial dysfunction support a prominent role for functional rather than anatomical abnormalities. However, attempts to reduce the high mortality in septic patients by manipulating the functional alterations have provided limited success. In recent years, the concept of septic cardiomyopathy has evolved, which implies alterations in the myocardial phenotype. This review includes an overview on the activation of the immune system and therapeutic approaches in sepsis, myocardial structural changes in the human septic heart, experimental models of sepsis, and cellular, molecular and functional myocardial changes seen in a variety of experimental sepsis models. The abnormal parameters discussed may emerge as therapeutic targets, for which modulation might provide beneficial effects on cardiovascular outcome and mortality in sepsis in the future.
Comparison of Quick Diagnosis Units and Conventional Hospitalization for the Diagnosis of Cancer in Spain: A Descriptive Cohort Study
Authors: Bosch Xavier , Moreno Pedro , Ríos Martín , Jordán Anna , López-Soto Alfonso
Published: September 2012

Objective: Quick diagnosis units (QDUs) in Spain provide patients with severe disease who would normally require hospitalization with the prompt and effective diagnosis they deserve. We compared the value and cost of a QDU and of conventional hospitalization in assessing patients with cancer. Methods: In a descriptive cohort study, 169 patients with a final diagnosis of cancer were prospectively evaluated between November 2008 and April 2010. We also analyzed a retrospective cohort of 53 randomly selected patients with neoplasia hospitalized during this period. In addition to the variables time to diagnosis and length of stay, we compared the costs of both models using microcosting techniques. Results: Colorectal cancer was the commonest cancer (26%). QDU patients were younger than hospitalized patients (68.3 vs. 74.7 years; p < 0.05), and there were also significant differences with respect to the source of referral (p < 0.00001) and destination (p < 0.00001), but not regarding diagnosis (p > 0.34), reason for consultation (p > 0.26) and time to diagnosis/length of stay (Wilcoxon rank sum test, p > 0.05). The mean costs for hospitalization were EUR 4,059.37 compared with EUR 601.84 in the QDU. Conclusion: For diagnostic purposes, cancer patients can be managed similarly in a QDU or in in-hospital settings, but the QDU model seems to incur fewer costs.
Inflammatory/Stress Feedback Dysregulation in Women with Fibromyalgia
Authors: Bote Maria E. , García Juan J. , Hinchado Maria D. , Ortega Eduardo
Published: September 2012

Objective: Although one of the current hypotheses of the aetiology of fibromyalgia (FM) syndrome involves inflammatory and neuroendocrine disorders, its biophysiology still remains unclear. The purpose of the present investigation was to study the systemic inflammatory and stress responses, as well as the innate response mediated by monocytes and neutrophils in FM patients. Methods: Twenty-five women diagnosed with primary FM and 20 age-matched healthy women (control group) were enrolled in the study. Circulating ‘neuroendocrine-stress’ biomarkers (CRH, ACTH, cortisol, NA, eHsp72, serotonin and IGF-1) were evaluated by ELISA. Serum IL-8 and CRP concentrations were also determined by ELISA, and inflammatory cytokine release by monocytes [IL-1β, TNFα, IL-6, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1) and RANTES] was evaluated by the Luminex BioPlex system. The phagocytic process of neutrophils (chemotaxis, phagocytosis and microbicide capacity) was also evaluated. Results: FM patients showed an inflammatory state accompanied by an altered stress response. This is mainly manifested by high circulating levels of IL-8 and CRP (in 100% of the FM group), high circulating levels of cortisol, and increased systemic levels of NA and eHsp72. There is also increased release of inflammatory cytokines (IL-1β, TNFα, IL-6, IL-10, IL-18 and MCP-1) by monocytes, and enhanced activation of the functional capacity of neutrophils (chemotactic, phagocytic and fungicidal activities). Conclusion: An inflammatory/stress feedback dysregulation underlies FM. Whether dysregulation of the stress response is the cause of the inflammatory dysregulation or vice versa is also discussed.
Compulsory Commitment to Care of Substance Misusers: International Trends during 25 Years
Authors: Israelsson Magnus , Gerdner Arne
Published: September 2012

Purpose: The study explores international trends in law on compulsory commitment to care of substance misusers (CCC), and two subtypes – civil CCC and CCC within criminal justice legislation – as well as maximum length and amount of applications of such care. Method: The time period covers more than 25 years, and a total of 104 countries and territories. The study is based on available data in three times of observation (1986, 1999 and 2009). Applications of CCC in number of cases are studied on European level for the years 2002–2006. Trends are analyzed using nonparametric tests and general linear models for repeated measures. Findings are discussed from contextual analysis. Result: There is a trend towards decrease in the number of countries worldwide having civil CCC legislation after the millennium, while CCC under criminal law has increased since the mid-1980s, resulting in some total net decrease. The shift results in longer mean duration of CCC and an increase in the number of cases sentenced. Conclusion: There is a risk that the shift from civil CCC to penal CCC implies more focus on young out-acting males in compulsory treatment and that the societal responsibility for more vulnerable persons might be neglected.
High-Flow Nasal Cannulae for Respiratory Support of Preterm Infants: A Review of the Evidence
Authors: Manley Brett J. , Dold Simone K. , Davis Peter G. , Roehr Charles C.
Published: September 2012

Background: High-flow nasal cannulae (HFNC) are gaining in popularity as a form of non-invasive respiratory support for preterm infants in neonatal intensive care units around the world. They are proposed as an alternative to nasal continuous positive airway pressure (NCPAP) in a variety of clinical situations, including post-extubation support, primary therapy from birth and ‘weaning’ from NCPAP. Objectives: To present and discuss the available evidence for the use of HFNC in the preterm population. Methods: An internet-based literature search for relevant, original research articles (both randomised studies and not) on the use of HFNC in preterm infants was undertaken. Results: A total of 19 studies were included in the review. Distending pressure generated by HFNC in preterm infants increases with increasing flow rate and decreasing infant size and varies according to the amount of leak around the prongs. HFNC may be as effective as NCPAP at improving respiratory parameters such as tidal volume and work of breathing in preterm infants, but probably only at flow rates >2 litres/min. The efficacy and safety of HFNC in preterm infants remain to be determined. Conclusions: There is growing evidence of the feasibility of HFNC as an alternative to other forms of non-invasive ventilation in preterm infants. However, there remains uncertainty about the efficacy and safety of HFNC in this population. Until the results of larger randomised trials are known, widespread use of HFNC to treat preterm infants cannot be recommended.
Twist Confers Chemoresistance to Anthracyclines in Bladder Cancer through Upregulating P-Glycoprotein
Authors: Chen Yule , Li Lei , Zeng Jin , Wu Kaijie , Zhou Jiancheng , Guo Peng , Zhang Dong , Xue Yan , Liang Liang , Wang Xinyang , Chang Luke S. , He Dalin
Published: September 2012

Background: The membrane transporter P-glycoprotein (P-gp) was found to mediate chemoresistance, which is one of the obstacles to effective chemotherapy in several types of human cancer. The transcription factor Twist, which has been reported to participate in cancer invasion and metastasis, also plays a vital role in the progression of chemoresistance. However, the effect of Twist on P-gp-related chemoresistance remains dubious. Methods and Results: We found that Twist can regulate the expression of P-gp and then confer resistance to anthracycline drugs in human bladder cancer cells. Firstly, Twist was found to be coexpressed with P-gp in human bladder cancer cells and tissues, which were associated with enhanced chemoresistance to anthracycline drugs. Secondly, knockdown of Twist by specific siRNA treatment significantly sensitized bladder cancer cells to anthracycline drugs via inhibiting P-gp expression. Bladder cancer cells that survived transient exposure to anthracycline drugs showed higher levels of P-gp expression and more nuclear localization of Twist than untreated cells. Conclusion: We report a novel mechanism of anthracycline chemoresistance in bladder cancer in which activated Twist mediates P-gp expression in addition to its antiapoptotic roles. Therapeutic strategies targeting Twist may improve the management of recurrent bladder cancer after chemotherapy.