bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of PR Interval on Outcomes Following Cardiac Resynchronization Therapy: A Secondary Analysis of the COMPANION Trial
Authors: LIN JEFFREY , BUHR KEVIN A. , KIPP RYAN 
Published: November 2016

Effect of PR Interval on CRT OutcomesBackgroundProlonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from CRT‐D regardless of whether left bundle branch block (LBBB) or non‐LBBB is present.Methods and ResultsA total of 308 patients enrolled in the optimal pharmacologic therapy (OPT) and 595 patients in the cardiac resynchronization therapy with defibrillation (CRT‐D) arms of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were stratified according to normal (≤230 ms) or prolonged PR interval (>230 ms). The incidence of all‐cause mortality (ACM) or hospitalization (primary endpoint) and ACM (secondary endpoint) was compared using Kaplan–Meier curves. Cox proportional hazards models for the primary and secondary endpoints were fit with LBBB status and baseline PR interval. CRT‐D treatment reduced both hospitalization/ACM (P = 0.002) and ACM (P = 0.003) compared to OPT. However, CRT‐D was increasingly more effective in reducing ACM hazard in patients with longer baseline PR intervals (P = 0.002) regardless of LBBB status. In particular, in the prolonged baseline PR interval subgroup, ACM was reduced with CRT‐D compared to OPT (P = 0.001) with little evidence of ACM reduction in the normal PR subgroup (P = 0.07).ConclusionsIn patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT‐D may improve survival regardless of LBBB status. In patients with non‐LBBB, a benefit from CRT‐D may occur with prolonged PR intervals.
Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes
Authors: DE POOTER JAN , EL HADDAD MILAD , DE BUYZERE MARC , ARANDA HERNANDEZ ALFONSO , CORNELUSSEN RICHARD , STEGEMANN BERTHOLD , RINALDI CHRISTOPHER A. , STERLINSKI MACIEJ , SOKAL ADAM , FRANCIS DARREL P. , JORDAENS LUC , STROOBANDT ROLAND X. , VAN HEUVERSWYN FREDERIC , TIMMERMANS FRANK 
Published: November 2016

Paced QRS Area Predicts CRT ResponseIntroductionVectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR).Methods and ResultsVCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl, YAmpl, ZAmpl, and 3DAmp) and QRS areas (XArea, YArea, ZArea, and 3DArea) in the orthogonal leads (X, Y, and Z) and in 3‐dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 μVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 μVs, IQR:10;57) and YArea (44 μVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl, Δ3DAmpl, ZArea, ΔZArea, Δ3DArea, and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement.ConclusionOf all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.
Randomized controlled trial comparing lactulose plus albumin versus lactulose alone for treatment of hepatic encephalopathy
Authors: Sharma Barjesh Chander , Singh Jatinderpal , Srivastava Siddharth , Sangam Alok , Mantri Alok Kumar , Trehanpati Nirupma , Sarin Shiv Kumar 
Published: November 2016

AbstractBackgroundHepatic encephalopathy (HE) is associated with poor prognosis and treatment of HE is primarily directed at the reduction of the blood ammonia levels. The study evaluated the efficacy and safety of albumin plus lactulose versus lactulose alone for treatment of overt HE.MethodsIn prospective randomized controlled trial, 120 patients with overt HE were randomized in two groups: group A lactulose plus albumin (n = 60) and group B lactulose alone (n = 60). Primary end point was complete reversal of HE, and secondary end points were mortality and hospital stay.ResultsA total of 120 patients (mean age 40.4 ± 9.3 years) were included in this study. Thirty‐six (30%) patients were in Child–Turcotte–Pugh (CTP) class B, and 84 (70%) were in CTP Class C. Mean CTP score was 9.8 ± 2.1, and model for end‐stage liver disease score was 26.1 ± 5.3. Twenty seven (22.5%) had grade 2, 57 (47.5%) had grade 3, and 36 (30%) had grade 4 HE at the time of admission. Forty‐five (75%) patients in group A compared with 32 (53.3%) patients in group B had complete reversal of HE (P = 0.03). Mortality was significantly lower in lactulose plus albumin group (11[18.3%]) versus lactulose alone (19 [31.6%], [P < 0.05]). There was significant decrease in levels of arterial ammonia, interleukin‐6, interleukin‐18, tumor necrosis factor‐alpha, and endotoxins after treatment in both groups; however, the delta decrease was significantly higher in group A compared with group B. Hospital stay was shorter in group A.ConclusionsCombination of lactulose plus albumin is more effective than lactulose alone in treatment of overt HE.
A novel function of TBK1 as a target of Cdon in oligodendrocyte differentiation and myelination
Authors: Wang Li‐Chun , Kennedy Timothy E. , Almazan Guillermina 
Published: November 2016

AbstractDuring central nervous system development, oligodendrocyte progenitors elaborate multiple branched processes to contact axons and initiate myelination. Using cultured primary rat oligodendrocytes (OLGs), we have recently demonstrated that a cell surface protein belonging to the immunoglobulin superfamily, cell adhesion molecule‐related, down‐regulated by oncogenes (Cdon), is important in initiating OLG differentiation and axon myelination by promoting the formation of branched cellular processes; however, the molecular mechanism by which Cdon regulates OLG differentiation is not known. Here, using Cdon immunoprecipitation (IP) and liquid chromatography–tandem mass spectrometry analysis, we identified serine/threonine kinase TANK‐binding kinase 1 (TBK1) as a candidate novel target of Cdon. We confirmed this interaction using co‐IP and immunofluorescence with TBK1 antibodies, showing that TBK1 partly co‐localizes with Cdon along cellular processes in puncta‐like structures. We show that TBK1 is expressed throughout OLG differentiation, and surprisingly, that levels of phosphorylated TBK1 (ser172) increase during OLG maturation, while total levels of TBK1 protein decrease. To investigate function, TBK1 expression was knocked down using siRNA in OLG primary cultures, reducing protein levels by 69%. Two myelin‐specific proteins, myelin basic protein and myelin‐associated glycoprotein, were similarly reduced when examined at day 2 and day 4 of OLG differentiation. Reduced Cdon or TBK1 expression also decreased Akt phosphorylation at Threonine 308 in OLG. Our findings provide evidence that a Cdon‐TBK1 complex is associated with Akt phosphorylation and early OLG differentiation.
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Protective effects of a novel nutritional and phytonutrient blend on ultraviolet radiation‐induced skin damage and inflammatory response through aging defense mechanisms
Authors: Wood Steven M , Mastaloudis Angela F , Hester Shelly N , Gray Russell , Kern Dale , Namkoong Jin , Draelos Zoe D 
Published: November 2016

SummaryBackgroundThe human body relies on several aging defense mechanisms (ADMs) to limit damage induced from pro‐aging stressors (aging aggressors). However, such protective mechanisms can be compromised, leading to accelerated aging. The skin provides a model to probe the effects of an oral nutritional intervention on ADMs in response to ultraviolet radiation (UVR)‐induced damage.ObjectiveTo determine whether supplementation with a novel nutritional and phytonutrient blend could protect against UVR‐induced skin damage and positively influence facial skin attributes and characteristics by bolstering ADMs.MethodsThirty‐six healthy, nonsmoking women (40–75 years) with Fitzpatrick skin types I and II were recruited. UVR‐induced erythema and the number of apoptotic cells were determined before (pre‐) and after 8‐week (post‐) supplementation. Other clinical variables included skin carotenoid concentrations, facial skin attributes and characteristics.ResultsEight‐week supplementation led to protection against UVR‐induced skin damage as evidenced by reductions in erythema at all three minimal erythema doses (MEDs) (9.1 to 7.4 [P = 0.10]; 15.8 to 13.6 [P = 0.02]; and 19.6 to 17.3 [P = 0.01] for one, two, and three MEDs and a reduction in the average number of apoptotic cells [11.3 to 5.3, P < 0.0001] pre‐ and post‐supplementation, respectively). Skin carotenoid concentrations increased from 28 111 Raman intensity units to 38 472 (P < 0.0001) along with noticeable improvements in facial skin attributes and characteristics: elasticity, transepidermal water loss, radiance, texture, and overall appearance (all P < 0.05) following supplementation.ConclusionEight weeks of oral supplementation positively impacted ADMs resulting in protection against UVR‐induced skin damage and improvements in facial skin attributes and characteristics.
The Social and Spatial Stratification of Vaccinal Patterns in Berlin Following Re‐Unification
Authors: Baur Nicole 
Published: November 2016

AbstractEfforts by health authorities to stress the importance of herd immunity in the light of a resurgence of seemingly vanquished childhood diseases have frequently met with poor response rates. Investigating whether reunified Berlin can achieve a desirable herd immunity of 80% ‐ 85% against diphtheria, this paper examines the potential influence of socio‐demographic variables (age, gender, social circumstances, migration background) on vaccine‐uptake. Secondly, it investigates historically diverging vaccinal policies in Berlin as well as recent changes to monitoring coverage in their effect on immunisation‐related behaviour.
The association between dentition status and sarcopenia in Japanese adults aged ≥75 years
Authors: Iwasaki M. , Kimura Y. , Ogawa H. , Wada T. , Sakamoto R. , Ishimoto Y. , Fujisawa M. , Okumiya K. , Ansai T. , Miyazaki H. , Matsubayashi K. 
Published: November 2016

SummarySarcopenia is an age‐related loss of muscle mass and muscle strength or physical performance. There are limited data on the association between oral health and sarcopenia. To test the hypothesis that impaired dentition status was associated with sarcopenia, we conducted a cross‐sectional study. A total of 272 community‐dwelling Japanese adults aged ≥75 years for whom data were available from comprehensive health examinations conducted in 2015 were included in this study. During dental examination, the number of natural teeth and occluding pairs of natural teeth was counted. In denture wearers, the fit of the removable dentures was also evaluated. The criteria proposed by the Asian Working Group for Sarcopenia were used to define sarcopenia. A multivariable logistic regression model was used to evaluate the association between dentition status and the presence of sarcopenia. The prevalence of sarcopenia was 25·7% (70/272). Compared to individuals with ≥10 occluding pairs of natural teeth, those with no occluding pairs of natural teeth had significantly higher risk of having sarcopenia (adjusted odds ratio, 3·37; 95% confidence interval, 1·07–10·61), after adjusting for possible confounders. In addition, compared to individuals with well‐fitting dentures, those with ill‐fitting dentures had significantly higher risk of having sarcopenia (adjusted odds ratio, 5·07; 95% confidence interval, 1·59–16·19). Our findings suggest that impaired dentition status is significantly associated with sarcopenia among community‐dwelling Japanese adults aged ≥75 years. Future longitudinal studies with larger, more diverse populations are necessary to validate our findings.
Lipiodol does not affect the tissue distribution of intravenous doxorubicin infusion in pigs
Authors: Lilienberg Elsa , Dubbelboer Ilse R , Sjögren Erik , Lennernäs Hans 
Published: November 2016

Abstract

Objectives
In liver cancer treatment, lipiodol is used as a pharmaceutical excipient to improve delivery of the cytostatic drug doxorubicin (DOX). As DOX and its metabolite doxorubicinol (DOXol) cause serious off-target adverse effects, we investigated the effects of drug-free lipiodol or ciclosporin (CsA) on the tissue distribution (Kp) of DOX and DOXol in relevant pig tissues.

Methods
Four treatment groups (TI–TIV) all received an intravenous DOX solution at 0 and 200 min. Before the second dose, the pigs received a portal vein infusion of saline (TI), lipiodol (TII), CsA (TIII) or lipiodol and CsA (TIV). After 6 h, the pigs were euthanised, and liver, kidney, heart and intestine samples were collected and analysed.

Key findings
The tissue DOX concentrations were highest in the kidney (TI–TIV). All the investigated tissues showed extensive DOX Kp. Lipiodol had no effect on the Kp of DOX to any of the tissues. However, the tissue concentrations of DOX were increased by CsA (in liver, kidney and intestine, P &lt; 0.05).

Conclusion
Lipiodol injected into the portal vein does not affect the tissue distribution of DOX and DOXol.
Telomeric localization of the Arabidopsis‐type heptamer repeat, (TTTAGGG)n, at the chromosome ends in Saccharina japonica (Phaeophyta)
Authors: Yang Qi‐Fan , Liu Li , Liu Yu , Zhou Zhi‐Gang 
Published: November 2016

Telomeres generally consist of short repeats of minisatellite DNA sequences and are useful in chromosome identification and karyotype analysis. To date, telomeres have not been characterized in the economically important brown seaweed Saccharina japonica, thus its full cytogenetic research and genetic breeding potential has not been realized. Herein, the tentative sequence of telomeres in S. japonica was identified by PCR amplification with primers designed based on the Arabidopsis‐type telomere sequence (TTTAGGG)n, which was chosen out of three possible telomeric repeat DNA sequences typically present in plants and algae. After PCR optimization and cloning, sequence analysis of the amplified products from S. japonica genomic DNA showed that they were composed of repeat units, (TTTAGGG)n, in which the repeat number ranged from 15 to 63 (n = 46). This type of repeat sequence was verified by a Southern blot assay with the Arabidopsis‐type telomere sequence as a probe. The digestion of S. japonica genomic DNA with the exonuclease Bal31 illustrated that the target sequence corresponding to the Arabidopsis‐type telomere sequence was susceptible to Bal31 digestion, suggesting that the repeat sequence was likely located at the outermost ends of the kelp chromosomes. Fluorescence in situ hybridizations with the aforementioned probe provided the initial cytogenetic evidence that the hybridization signals were principally localized at both ends of S. japonica chromosomes. This study indicates that the telomeric repeat of the kelp chromosomes is (TTTAGGG)n which differs from the previously reported (TTAGGG)n sequence in Ectocarpus siliculosus through genome sequencing, thereby suggesting distinct telomeres in brown seaweeds.
Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect‐acting antiviral era
Authors: McDonald S. A. , Innes H. A. , Aspinall E. , Hayes P. C. , Alavi M. , Valerio H. , Goldberg D. J. , Hutchinson S. J. 
Published: November 2016

SummaryAt a population level, little is known regarding the risk of liver‐ and nonliver‐related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)‐infected patients with decompensated cirrhosis (DC). This large‐scale national record‐linkage study estimates these outcomes following first hospital admission for DC. Record‐linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow‐up the disease course of all identified HCV‐diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994‐2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994‐1999 to 541 in 2009‐2013), with no evidence for any improvement in the relative risks of liver‐related or all‐cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver‐ and a nonliver‐related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5‐year cumulative incidence of liver‐related mortality, nonliver‐related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV‐infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.
Protective efficacy and hepatitis B virus clearance in mice enhanced by cell‐mediated immunity with novel prime‐boost regimens
Authors: Chuai X. , Chen P. , Chen H. , Wang W. , Deng Y. , Ruan L. , Li W. , Tan W. 
Published: November 2016

SummaryIn this study, anti‐hepatitis B virus (HBV) immunity was evaluated in mice using several regimens of the HBV recombinant protein vaccine HBSS1 that expressed in CHO cells containing S (1‐223 aa) and preS1 (21‐47 aa) and recombinant adenovirus rAdSS1 vaccine. Further, the protective efficacy of these vaccine regimens was studied in a mouse model. High titres of antigen‐specific antibodies and neutralizing activity were elicited in mice after vaccination. However, robust multi‐antigen (preS1 and S)‐specific cell‐mediated immunity (CMI) was only detected in mice primed with HBSS1 and boosted with rAdSS1. Moreover, functional T‐cell responses with high levels of cytokines and antigen‐specific cytotoxic T‐cell responses (CD107a+CD8+) were also detected in the mice. Rapid clearance of hepatitis B surface antigen and HBV DNA in blood and significantly decreased hepatitis B envelope antigen levels were observed in mice immunized with the heterogeneous prime‐boost vaccine after hepatitis B virus challenge by hydrodynamic injection (HI) of pCS‐HBV1.3. The clearance of HBV correlated well with antigen‐specific CMI (Th1 and CTL responses) and cytokine profiles (IFN‐γ, TNF‐α, IL‐2) elicited by vaccination. Taken together, our results might contribute to the development of new human HBV vaccines and a better understanding of the mechanisms underlying immune protection and clearance of hepatitis B virus infection.
Role of primary T‐cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort
Authors: Islam N. , Krajden M. , Gilbert M. , Gustafson P. , Yu A. , Kuo M. , Chong M. , Alvarez M. , Wong J. , Tyndall M. W. , Janjua N. Z. 
Published: November 2016

SummaryT‐cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T‐cell deficiency along with other factors on the spontaneous clearance of HCV in a large population‐based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990‐2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV‐positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46 783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T‐cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32‐0.94), and higher in females (aOR: 1.61, 95% CI: 1.54‐1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93‐2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T‐cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.
Pharmacokinetics and tolerability of a new formulation of omeprazole in the horse
Authors: Di Salvo A. , Busechian S. , Zappulla F. , Marchesi M. C. , Pieramati C. , Orvieto S. , Boveri M. , Predieri P. G. , Rueca F. , della Rocca G. 
Published: November 2016

A new formulation of omeprazole in gastro‐resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty‐four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4 mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which were treated orally once a day for 90 days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre‐established time points, were used to determine the concentration–time curves of omeprazole. The treatments were found to be safe and well tolerated by the horses. The serum hematological and biochemical values were within reference ranges for the entire observational time. No accumulation of the drug was found after 29 days of treatment. LowerCmaxandAUCs were obtained at the 29th day of treatment.
Labor Force Participation of Women in the EU – What Role do Family Policies Play?
Authors: Gehringer Agnieszka , Klasen Stephan 
Published: November 2016

AbstractWe empirically study the role of different family policies in affecting women's labor market behavior in the European Union. Women tend to assume more family duties than men and, consequently, often participate less in the labor market. Family policies aim to support families in general while a particular focus is on helping women to reconcile family duties with labor market participation. Their impact, however, is not clear, especially when it comes to different forms of labor market activity. We use a static and dynamic panel econometric framework examining the link between financial support for four types of family policies and labor force participation as well as (part‐time and full‐time) employment. The results suggest no stable significant impact of expenditures on family policies on overall labor force participation. However, higher spending on family allowance, cash benefits, and daycare benefits appears to promote part‐time employment, whereas only spending on parental leave schemes is a significant positive determinant of women's full‐time employment.