bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverging shrub and tree growth from the Polar to the Mediterranean biomes across the European continent
Authors: Pellizzari Elena , Camarero Jesus Julio , Gazol Antonio , Granda Elena , Shetti Rohan , Wilmking Martin , Moiseev Pavel , Pividori Mario , Carrer Marco
Published: November 2016

Climate warming is expected to enhance productivity and growth of woody plants, particularly in temperature‐limited environments at the northernmost or uppermost limits of their distribution. However, this warming is spatially uneven and temporally variable, and the rise in temperatures differently affects biomes and growth forms. Here, applying a dendroecological approach with generalized additive mixed models, we analysed how the growth of shrubby junipers and coexisting trees (larch and pine species) responds to rising temperatures along a 5000‐km latitudinal range including sites from the Polar, Alpine to the Mediterranean biomes. We hypothesize that, being more coupled to ground microclimate, junipers will be less influenced by atmospheric conditions and will less respond to the post‐1950 climate warming than coexisting standing trees. Unexpectedly, shrub and tree growth forms revealed divergent growth trends in all the three biomes, with juniper performing better than trees at Mediterranean than at Polar and Alpine sites. The post‐1980s decline of tree growth in Mediterranean sites might be induced by drought stress amplified by climate warming and did not affect junipers. We conclude that different but coexisting long‐living growth forms can respond differently to the same climate factor and that, even in temperature‐limited area, other drivers like the duration of snow cover might locally play a fundamental role on woody plants growth across Europe.
Accurate and Precise Silicon Isotope Analysis of Sulfur‐ and Iron‐Rich Samples by MC‐ICP‐MS
Authors: Chen Xinyang , Lapen Thomas J. , Chafetz Henry S.
Published: November 2016

Silicon isotope determination of sulfur‐rich samples by MC‐ICP‐MS can be challenging because cation‐exchange chromatography used for Si purification does not efficiently remove anionic sulfur species. Results for pure Si standard solutions with addition of sulfate showed shifts of up to +1.04 ± 0.10‰ (2s) in δ30Si. Doping of both standard solutions and samples with S to a fixed S/Si ratio can eliminate the relative change in instrumental mass fractionation due to variable S/Si in samples and also boosts the relative sensitivity of Si by up to 66%. Moreover, Fe hydroxide precipitation during sample processing adsorbs Si resulting in isotopic fractionations. Tests using Fe‐rich samples showed that this could be a major factor for observed shifts in δ30Si. Acidification of the sample and standard solutions to a pH < 1 aggressively dissolved any Fe hydroxide precipitates, even in relatively Fe‐rich samples such as chondrite meteorites. The pH values of the sample solutions were subsequently adjusted to a range of 2–3 by adding ultra‐pure NaOH solutions. The combination of sulfur doping and the pH adjustment protocol ensured a full recovery of Si and proved to be an efficient and reliable method for Si isotope determination of S‐ and Fe‐rich materials.
Differences in Topographical Pressure Pain Sensitivity Maps of the Scalp Between Patients With Migraine and Healthy Controls
Authors: Barón Johanna , Ruiz Marina , Palacios‐Ceña María , Madeleine Pascal , Guerrero Ángel L. , Arendt‐Nielsen Lars , Fernández‐de‐las‐Peñas César
Published: November 2016

Objective

To investigate differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls considering the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the symptoms.

Background

It seems that the trigeminal area is sensitized in migraine. No study has investigated topographical pressure sensitivity maps of the scalp in patients with migraine.

Methods

Pressure pain thresholds (PPTs) were assessed from 21 points distributed over the scalp in 86 patients with episodic migraine, 76 with chronic migraine, and 42 healthy age and matched healthy controls in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of migraine, anxiety, and depression (Hospital Anxiety and Depression Scale, HADS) were collected.

Results

The multivariate ANCOVA revealed significant differences in PPT between points (F = 55.674; P < .001) and groups (F = 5.316; P = .006), but not sides (F = 0.880; P = .417). No significant effect of gender (F = 0.897; P = .656), depression (F = 1.109; P = .220), or anxiety (F = 0.981; F = 0.569) was found. Post hoc comparisons revealed: (1) lower PPTs in both migraine groups than in healthy controls in all points (P < .001); (2) no significant differences between chronic or episodic migraine (P > .335) except for Fp1 (P = .045) and Fp2 (P = .017) points where subjects with chronic migraine had lower PPTs than those with episodic migraine; (3) no differences between bilateral/unilateral migraine (P > .417). An anterior to posterior gradient was found, with the lowest PPTs located in frontal regions and the highest PPTs in occipital areas (all groups, P < .001).

Conclusions

We found that patients with migraine exhibited generalized pressure pain hypersensitivity in the head as compared to healthy controls and that hypersensitivity was similar between episodic/chronic and unilateral/bilateral migraine. Topographical pressure pain sensitivity maps revealed an anterior to posterior gradient of pressure pain sensitivity in both migraine and control groups.
Gender Differences in the Use of Complementary and Alternative Medicine and Their Association With Moderate Mental Distress in U.S. Adults With Migraines/Severe Headaches
Authors: Rhee Taeho Greg , Harris Ila M.
Published: November 2016

Objective

We examined whether the prevalence of complementary and alternative medicine (CAM) use varies by gender, and assessed the interaction of gender and CAM use on moderate mental distress (MMD) in U.S. adults with migraines/severe headaches.

Methods

We used data from the 2012 National Health Interview Survey, which represents non‐institutionalized U.S. adults with migraines/severe headaches (n = 4645 unweighted). Using a cross‐sectional design with survey sampling techniques, we conducted descriptive analyses for prevalence of CAM use by gender. Multivariate logistic regression analyses were run to investigate potential roles of migraines/severe headaches and CAM use on MMD by gender.

Results

The overall prevalence of past year CAM use was 44.4%. Women consistently used CAM more frequently than men (P = .004). The most commonly used CAM types included herbal supplements (22.2%), massage (14.2%), and chiropractic/osteopathic (13.9%). After controlling for covariates, the odds of MDD were increased by the presence of migraines/severe headaches (P < .001) and the use of any CAM (P < .001). The interaction effect of migraines/severe headaches and CAM use decreased the odds of MMD by 27% in women (P < .05), but not in men.

Conclusion

Women used CAM more frequently than men among adults with migraines/severe headaches in the United States. In addition, the interaction of gender and CAM use exists; the CAM use was associated with decreased odds of MMD among women only, suggesting that women with migraines/severe headaches may have benefited from CAM for their mental distress. Future research is needed to explore why such patterns vary by gender.
The probiotic role of Lactobacillus plantarum in reducing risks associated with cardiovascular disease
Authors: Liu Dong‐Mei , Guo Jun , Zeng Xin‐An , Sun Da‐Wen , Brennan Charles S. , Zhou Quan‐Xing , Zhou Jin‐Song
Published: November 2016

A novel strain of Lactobacillus plantarum DMDL 9010 (CGMCC No. 5172) was isolated from naturally fermented mustard. The potential cholesterol reduction effects of this strain were investigated using an in vivo model. The results showed that L. plantarum DMDL 9010 at a dose of 109 cells per day significantly reduced (P ≤ 0.05) serum total cholesterol (TC), low‐density lipoprotein cholesterol content (LDL‐C) levels and atherosclerosis index (AI) by 23.03%, 28.00% and 34.03%, respectively, while L. plantarum DMDL 9010 did not exhibit a significant effect on reducing serum triglycerides (TG) and increasing the serum high‐density lipoprotein cholesterol content (HDL‐C) in experimental rats (P > 0.05). The morphological and pathological changes in the liver illustrated that L. plantarum DMDL 9010 protected the rats against hepatocyte steatosis. Additionally, a high dose of L. plantarum DMDL 9010 was shown to exhibit a positive cholesterol‐lowering effect through decreasing the liver cholesterol (−33.20%) and triglyceride (−40.86%) levels, and increasing significantly (P ≤ 0.05) faecal cholesterol (+31.07%) and bile acid excretion (+70.18%). The results demonstrated that L. plantarum DMDL 9010 acted in a dose‐dependent way to decrease serum and total hepatic cholesterol and triglyceride and enhance faecal excretion of bile acids. In conclusion, these findings suggest that L. plantarum DMDL 9010 has potential to be explored as a probiotic for hypercholesterolaemic preventive and therapeutic.
Solubility, functional properties, ACE‐I inhibitory and DPPH scavenging activities of Alcalase hydrolysed soy protein hydrolysates
Authors: Horax Ronny , Vallecios Mariela Serrano , Hettiarachchy Navam , Osorio Luis Fernando , Chen Pengyin
Published: November 2016

Soy proteins are less soluble at acidic pH value, which impedes their utilisation in acidic beverages. Soy protein isolate (SPI) was hydrolysed using varying Alcalase concentrations (0.0001–2.0 U g−1 protein) at different pHs (3.0–4.0). Degree of hydrolysis (DH) of soy protein hydrolysates (SPH) at pH 3.0, 3.5 and 4.0 were 5.0–10.7%, 2.3–6.1% and 0–5.4%, respectively, while solubilities ranged from 70.7 to 74.9%, 18.8 to 51.2% and 7.1 to 40.4%, respectively. The highest solubility (74.9%) was observed at pH 3.0 with 1.5 U Alcalase per g protein (DH = 9.2%). Emulsifying activities of SPHs at pH 3.0 and 4.0 ranged from 0.49 to 0.63 AU and 0.19 to 0.24 AU, respectively, while the emulsifying stabilities were 12.2–14.7 min and 18.7–56.0 min, respectively. The foaming capacity at pH 3.0 and 4.0 was 44.9–46.3 mL and 31.2–41.3 mL, respectively, whereas the foaming stability was 25.5–35.2 min and 12.8–15.1 min, respectively. However, hydrolysates had an insignificant effect on ACE‐I inhibitory and DPPH scavenging activities in comparison with SPI.
Childhood obesity prevention cluster randomized trial for Hispanic families: outcomes of the healthy families study
Authors: Hull P. C. , Buchowski M. , Canedo J. R. , Beech B. M. , Du L. , Koyama T. , Zoorob R.
Published: November 2016

Background

Obesity prevalence is disproportionately high among Hispanic children.

Objectives

The Healthy Families Study assessed the efficacy of a culturally targeted, family‐based weight gain prevention intervention for Hispanic immigrant families with children ages 5–7 years.

Methods

The study used a two‐group, cluster randomized trial design, assigning 136 families (clusters) to the active intervention (weight gain prevention) and 136 families to attention control (oral health). The active intervention included a 4‐month intensive phase (eight classes) and an 8‐month reinforcement phase (monthly mail/telephone contact). Children's body mass index z‐score (BMI‐Z) was the primary outcome.

Results

The BMI‐Z growth rate of the active intervention group did not differ from the attention control group at short‐term follow‐up (median 6 months; 168 families, 206 children) or long‐term follow‐up (median 16 months; 142 families, 169 children). Dose response analyses indicated a slower increase in BMI‐Z at short term among overweight/obese children who attended more intervention classes. Moderate physical activity on weekends increased at short term. Weekend screen time decreased at short term among those attending at least one class session.

Conclusion

Low class attendance likely impacted intention‐to‐treat results. Future interventions targeting this population should test innovative strategies to maximize intervention engagement to produce and sustain effects on weight gain prevention.
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 Outcomes

Background

Prolonged 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 Results

A 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).

Conclusions

In 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 Response

Introduction

Vectorcardiographic (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 Results

VCGs 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.

Conclusion

Of 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

Background

Hepatic 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.

Methods

In 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.

Results

A 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.

Conclusions

Combination 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

During 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

Background

The 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.

Objective

To 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.

Methods

Thirty‐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.

Results

Eight‐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.

Conclusion

Eight 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

Efforts 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

Sarcopenia 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

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 < 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

At 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

In 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

T‐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.
Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover
Authors: Hussein H. , Dulin J. , Smanik L. , Drost W. T. , Russell D. , Wellman M. , Bertone A.
Published: November 2016

Our investigations evaluated the effect of VEL‐0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX‐1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis of plasma bone biomarkers (CTX‐1 and osteocalcin), poststudy bone fluorescent labeling, and bone biopsy were performed. Bone specimens were further processed for microcomputed tomography and bone histomorphometry. Each dose of this CatKI transiently inhibited plasma CTX‐1 (reflecting inhibition of bone collagen resorption) and increased bone plasma osteocalcin concentrations, with no detectable adverse effect on normal bone turnover in the face of exercise. Bone morphology, density, and formation rate were not different between control and treated group. Further investigation of CatK inhibition in abnormal bone turnover is required in animals with bone diseases.
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

We 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.
Hepatocellular carcinomas with intracellular hyaline bodies have a poor prognosis
Authors: Aigelsreiter Ariane , Neumann Jens , Pichler Martin , Halasz Judith , Zatloukal Kurt , Berghold Andrea , Douschan Philipp , Rainer Florian , Stauber Rudolf , Haybaeck Johannes , Denk Helmut , Lackner Carolin
Published: November 2016

Background & Aims

Mallory‐Denk bodies (MDBs) and intracellular hyaline bodies (IHBs) are cytoplasmic inclusions found in a subset of hepatocellular carcinoma (HCC). MDBs are mainly composed of the intermediate filament proteins keratin (K) 8 and K18, the cellular stress‐ and adapter‐protein sequestosome 1/p62 (p62) and ubiquitin, whereas IHBs consist of p62 and/or ubiquitin. Of note, cytoplasmic inclusions containing p62 can serve as markers of suppressed autophagy, which in turn has been associated with poor prognosis. The aim of this study was to evaluate the prognostic significance of p62‐containing MDB and IHB in patients with HCC.

Methods

Ninety resected HCCs were assessed by H&E histology for MDB or IHB, and their presence was confirmed by immunohistochemistry using K8/18, p62 and ubiquitin antibodies. The prognostic impact of inclusions was assessed using Kaplan‐Meier and multivariate Cox proportional model.

Results

Mallory‐Denk bodies and/or IHB were found in about 50% of HCC. Both types of inclusions were seen in 21%, MDB only in 19% and IHB only in 10% of cases. The presence of MDB in tumours was associated with the steatohepatitic variant of HCC, which also showed fatty change, ballooning of tumour cells, MDBs, inflammation and pericellular fibrosis (P<.001). In contrast, IHBs were not associated with steatohepatitic morphology but were associated with significantly shorter overall survival (P=.006). Multivariate analysis revealed macroscopic vascular invasion (P=.045) and presence of IHB in HCC cells (P=.005) as independently associated with overall survival.

Conclusions

Intracellular hyaline bodies and macroscopic vascular invasion identify a subset of HCC patients with poor prognosis.
Evolution, genomics and epidemiology of Pseudomonas syringae
Authors: Baltrus David A. , McCann Honour C. , Guttman David S.
Published: November 2016

A remarkable shift in our understanding of plant‐pathogenic bacteria is underway. Until recently, nearly all research on phytopathogenic bacteria was focused on a small number of model strains, which provided a deep, but narrow, perspective on plant–microbe interactions. Advances in genome sequencing technologies have changed this by enabling the incorporation of much greater diversity into comparative and functional research. We are now moving beyond a typological understanding of a select collection of strains to a more generalized appreciation of the breadth and scope of plant–microbe interactions. The study of natural populations and evolution has particularly benefited from the expansion of genomic data. We are beginning to have a much deeper understanding of the natural genetic diversity, niche breadth, ecological constraints and defining characteristics of phytopathogenic species. Given this expanding genomic and ecological knowledge, we believe the time is ripe to evaluate what we know about the evolutionary dynamics of plant pathogens.
Music interventions for dental anxiety
Authors: Bradt J , Teague A
Published: November 2016

Anxiety is a significant issue in the dental care of adults and children. Dental anxiety often leads to avoidance of dental care which may result in significant deterioration of oral and dental health. Non‐pharmacological anxiety management interventions such as music listening are increasingly used in dental care. Although efficacy for music's anxiolytic effects has been established for pre‐operative anxiety, findings regarding the use of music listening for dental anxiety are inconclusive, especially for children. The use of music for passive distraction may not be adequate for children and highly anxious adults. Instead, interventions offered by a trained music therapist may be needed to optimize music's anxiolytic impact. Music therapy interventions are individualized to the patient's presenting needs and geared at enhancing patients’ active engagement in the management of their anxiety. Interventions may include (i) active refocusing of attention, (ii) music‐guided deep breathing, (iii) music‐assisted relaxation, and (iv) music‐guided imagery. In addition, music therapists can teach patients music‐based anxiety management skills prior to dental treatments, offer them the opportunity to express emotions related to the upcoming procedure, and help them gain a sense of control and safety. Clinical guidelines for the use of music listening by dental practitioners are offered.
Onychophoran‐like myoanatomy of the Cambrian gilled lobopodian Pambdelurion whittingtoni
Authors: Young Fletcher J. , Vinther Jakob
Published: November 2016

Arthropods are characterized by a rigid, articulating, exoskeleton operated by a lever‐like system of segmentally arranged, antagonistic muscles. This skeletomuscular system evolved from an unsegmented body wall musculature acting on a hydrostatic skeleton, similar to that of the arthropods’ close relatives, the soft‐bodied onychophorans. Unfortunately, fossil evidence documenting this transition is scarce. Exceptionally‐preserved panarthropods from the Cambrian Lagerstätte of Sirius Passet, Greenland, including the soft‐bodied stem‐arthropod Pambdelurion whittingtoni and the hard‐bodied arthropods Kiisortoqia soperi and Campanamuta mantonae, are unique in preserving extensive musculature. Here we show that Pambdelurion's myoanatomy conforms closely to that of extant onychophorans, with unsegmented dorsal, ventral and longitudinal muscle groups in the trunk, and extrinsic and intrinsic muscles controlling the legs. Pambdelurion also possesses oblique musculature, which has previously been interpreted as an arthropodan characteristic. However, this oblique musculature appears to be confined to the cephalic region and first few body segments, and does not represent a shift towards arthropodan myoanatomy. The Sirius Passet arthropods, Kiisortoqia and Campanamuta, also possess large longitudinal muscles in the trunk, although, unlike Pambdelurion, they are segmentally divided at the tergal boundaries. Thus, the transition towards an arthropodan myoanatomy from a lobopodian ancestor probably involved the division of the peripheral longitudinal muscle into segmented units.
5‐ALA‐mediated photodynamic therapy reduces the parasite load in mice infected with Leishmania braziliensis
Authors: Souza D. M. , Alves P. M. , Silva M. L. F. , Paulino T. P. , Coraspe H. O. , Mendonça M. M. S. , Ribeiro B. M. , da Silva M. V. , Rodrigues Júnior V. , Rodrigues D. B. R.
Published: November 2016

Photodynamic therapy (PDT) has proven to be an effective alternative for the treatment of cutaneous leishmaniasis. Skin lesions consist of ulcers with well‐defined raised edges, and granular floor. Th1 immune response is the protective profile in patients infected with Leishmania. In this study, the photodynamic therapy with 5‐aminolevulinic acid, the parasitic load, and the modulation of the immune response was evaluated in mice infected with Leishmania braziliensis. Balb/c mice were infected with L. braziliensis and subsequently treated with three sections of PDT. The parasite load and mRNA expression of cytokines (IFN‐γ, IL‐4, IL‐17, IL‐22, IL‐27, IL‐10) and transcription factors (GATA‐3, Foxp3 and T‐bet) were analysed by quantitative PCR. The parasite load in the treated group was significantly lower than in the untreated group (P<.0001); in PDT treated animals, we observed an increase in IFN‐γ and T‐bet mRNA (P=.012 and P=.0071). There was a significant reduction in mRNA expression of IL‐22 associated with an increased expression of IL‐27 mRNA in the animals treated with light only (P=.0001). 5‐ALA associated with photodynamic therapy promotes a reduction in parasite load and an increased expression of IFN‐γ and T‐bet mRNA.
Identification of lactoferrin and glutamate receptor‐interacting protein 1 in bovine cervical mucus: A putative marker for oestrous detection
Authors: Lee WY , Park MH , Kim KW , Song H , Kim KB , Lee CS , Kim NK , Park JK , Yang BC , Oh KB , Im GS , Chung HJ
Published: November 2016

Contents

Accurate detection of oestrus is important for artificial insemination. The aim of this study was to identify oestrous‐specific bovine cervical mucus proteins that could be used to determine the optimal time for artificial insemination. Non‐oestrous and controlled internal drug release (CIDR)‐induced oestrous‐stage mucus proteins were purified and subjected to surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis and MALDI‐TOF/TOF. Among differentially expressed proteins, lactoferrin (LF) and glutamate receptor‐interacting protein 1 (GRIP1) showed a twofold increase during the CIDR‐induced oestrous stage compared to the levels in non‐oestrous stage in bovine cervical mucus. The RT‐PCR, Western blotting and immunohistochemistry results showed that LF and GRIP1 expression was significantly increased during the oestrous stage in the uterus. This study demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not during the non‐oestrous stage, suggesting that cervical mucus LF and GRIP1 are useful oestrous detection markers in cattle.