bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of clinical or haemodynamic rebound after abrupt interruption of beta‐blockers in patients with cirrhosis
Authors: Payancé A. , Bissonnette J. , Roux O. , Elkrief L. , Gault N. , Francoz C. , Nekachtali O. , Soubrane O. , Lebrec D. , Valla D. , Durand F. , Rautou P.‐E.
Published: March 2016

Background

Beta‐blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta‐blockers is based on an animal study and on isolated case reports of variceal bleeding.

Aim

To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta‐blockers.

Methods

We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: ‘no beta‐blockers’ including patients not receiving beta‐blockers; ‘≤1 day’, ‘2–3 days’ and ‘≥4 days’ classified according to the time patients had interrupted beta‐blockers before catheterisation. Results were expressed as median (interquartile range).

Results

A total of 150 patients were included. Among the 25 patients in the groups ‘2–3 days’ and ‘≥4 days’, median duration of beta‐blockers interruption was 4 (3–6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta‐blockers. After adjustment, beta‐blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the ‘≥4 days’ group [4.6 L/min/m2 (3.5–5.1)] than in the ‘≤1 day’ group [3.4 (2.6–4.0); P = 0.001] or in the ‘2–3 days’ group [3.1 (2.7–3.7); P = 0.007], but not different from the ‘no beta‐blockers’ group.

Conclusions

Abrupt interruption of beta‐blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta‐blockers in patients with cirrhosis may not require particular dosing or surveillance.
Responsiveness of beef cattle (Bos taurus) to human approach, novelty, social isolation, restraint and trade‐offs between feeding and social companionship
Authors: Hirata Masahiko , Kubo Shotaro , Taketomi Ikuko , Matsumoto Yuka
Published: March 2016

This study investigated responsiveness of beef cattle to various environmental stimuli by subjecting 15–16 Japanese Black cows to five tests repeated twice. Within individual behavioral measures, cows were moderately (repeatability = 0.54–0.70) or highly (repeatability = 0.74–0.89) consistent in flight distance during grazing and resting in the human approach tests, maximum distance from the group pen and the number of total and different feed tub visits in the feeding–sociability trade‐off test, and unwillingness to enter the restraint, movement under restraint and flight speed after release from restraint in the social isolation and restraint test. By contrast, cows were not consistent in the latency to make the first contact and the number of contacts with novel object(s) in the novelty test (repeatability = 0.24–0.39). Across behavioral measures in different tests, cows showed no consistency (P ≥ 0.05) in any combinations of measures from the two human approach tests, the trade‐off test and the social isolation and restraint test. In conclusion, human approach (particularly during resting), feeding–sociability trade‐off and social isolation and restraint situations can be used for evaluating personality in Japanese Black cows, while the value of the novelty test needs to be reexamined.
The TRPA1 Activator Allyl Isothiocyanate (AITC) Contracts Human Jejunal Muscle: Pharmacological Analysis
Authors: Sandor Zsolt , Dekany Andras , Kelemen Dezsö , Bencsik Timea , Papp Robert , Bartho Lorand
Published: March 2016

The contractile effect of AITC (300 μM) on human jejunal longitudinal strips was inhibited by the TRPA1 antagonist HC 030031 and atropine or scopolamine, but was insensitive to tetrodotoxin, purinoceptor antagonists or capsaicin desensitization. It is concluded that TRPA1 activation stimulates a cholinergic mechanism in a tetrodotoxin‐resistant manner.
Accumulating evidence for a role of TCF7L2 variants in bipolar disorder with elevated body mass index
Authors: Cuellar‐Barboza Alfredo B , Winham Stacey J , McElroy Susan L , Geske Jennifer R , Jenkins Gregory D , Colby Colin L , Prieto Miguel L , Ryu Euijung , Cunningham Julie M , Frye Mark A , Biernacka Joanna M
Published: March 2016

Objectives

Bipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome‐wide association study, we found that BMI modified the association of rs12772424 – a common variant in the gene encoding transcription factor 7‐like 2 (TCF7L2) – with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF7L2 single nucleotide polymorphisms (SNPs) to explore further the association of BD with the TCF7L2–BMI interaction.

Methods

Using a sample of 662 BD cases and 616 controls, we conducted SNP‐level and gene‐level tests to assess the evidence for an association between BD and the interaction of BMI and genetic variation in TCF7L2. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL) analysis.

Results

The analysis provided independent evidence of an rs12772424–BMI interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP marginal effects on BD, the TCF7L2–BMI interaction was significant at the gene level (p = 0.042), with seven of the 26 SNPs showing SNP–BMI interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF7L2 expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway.

Conclusions

The current study provides further evidence suggesting that TCF7L2 involvement in BD risk may be regulated by BMI. Detailed, prospective assessment of BMI, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association.
Sequential detection of learning in cognitive diagnosis
Authors: Ye Sangbeak , Fellouris Georgios , Culpepper Steven , Douglas Jeff
Published: March 2016

In order to look more closely at the many particular skills examinees utilize to answer items, cognitive diagnosis models have received much attention, and perhaps are preferable to item response models that ordinarily involve just one or a few broadly defined skills, when the objective is to hasten learning. If these fine‐grained skills can be identified, a sharpened focus on learning and remediation can be achieved. The focus here is on how to detect when learning has taken place for a particular attribute and efficiently guide a student through a sequence of items to ultimately attain mastery of all attributes while administering as few items as possible. This can be seen as a problem in sequential change‐point detection for which there is a long history and a well‐developed literature. Though some ad hoc rules for determining learning may be used, such as stopping after M consecutive items have been successfully answered, more efficient methods that are optimal under various conditions are available. The CUSUM, Shiryaev–Roberts and Shiryaev procedures can dramatically reduce the time required to detect learning while maintaining rigorous Type I error control, and they are studied in this context through simulation. Future directions for modelling and detection of learning are discussed.
Live imaging of transforming growth factor‐β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid
Authors: Takaoka Saori , Kamioka Yuji , Takakura Kanako , Baba Ai , Shime Hiroaki , Seya Tsukasa , Matsuda Michiyuki
Published: March 2016

Transforming growth factor‐β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live‐imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer‐based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee‐TAK1, responded to stress‐inducing reagents such as anisomycin, tumor necrosis factor‐α, and interleukin1‐β. The anisomycin‐induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)‐7‐oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee‐TAK1 were implanted into mice and observed through imaging window by two‐photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee‐TAK1 is a versatile tool to monitor cellular stress in cancer tissues.
Reduction of the expression and production of adhesion molecules and chemokines by brain endothelial cells in response to tumor necrosis factor‐α and interleukin‐17 in hypothermia
Authors: Matsui Tomohiro , Yoshida Yusuke
Published: March 2016

Objective

The upregulation of adhesion molecules and chemokines might facilitate the recruitment and infiltration of inflammatory cells into injured brain tissue, leading to enhanced post‐ischemic brain inflammation and exacerbated brain injury. Here we examined the effects of hypothermia and hyperthermia on the expression and production of adhesion molecules and chemokines by brain endothelial cells in response to tumor necrosis factor (TNF)‐α and interleukin (IL)‐17 in an attempt to identify the mechanisms responsible for the neuroprotection conferred by therapeutic hypothermia.

Methods

Brain endothelial bEnd.3 cells were stimulated with TNF‐α or IL‐17 under hypothermia (33°C), normothermia (37°C) or hyperthermia (39°C). Levels of mRNA expression and protein production of a number of adhesion molecules and chemokines were measured.

Results

In TNF‐α‐stimulated bEND.3 cells, the mRNA expression of adhesion molecules, intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 was reduced by hypothermia compared with normothermia. The production of chemokines, macrophage inflammatory protein‐2 (MIP‐2/CXCL2), interferon‐γ‐inducible protein‐10 (IP‐10/CXCL10) and monocyte chemoattractant protein‐1 (MCP‐1/CCL2) was reduced by hypothermia, but augmented by hyperthermia. In IL‐17‐stimulated bEND.3 cells, the mRNA expression of IP‐10/CXCL10, and the production of MIP‐2/CXCL2 and MCP‐1/CCL2 were reduced by hypothermia compared with normothermia.

Conclusions

Therapeutic hypothermia might suppress the recruitment of inflammatory cells to the central nervous system by directly reducing the expression and production of cell adhesion molecules and chemokines by brain endothelial cells in response to stimulation with TNF‐α and IL‐17. Conversely, the hyperthermic state might promote such inflammatory responses by directly augmenting the TNF‐α‐stimulated brain endothelial cell production of chemokines.
Costs and Opportunities for Preserving Coastal Wetlands under Sea Level Rise
Authors: Runting Rebecca K. , Lovelock Catherine E. , Beyer Hawthorne L. , Rhodes Jonathan R.
Published: March 2016

Rises in sea level can alter the distribution of coastal wetlands through migration landward and loss due to inundation. The expansion of coastal developments can prevent potential wetland migration, exacerbating loss as sea levels rise. Pre‐emptive planning to set aside key coastal areas for wetland migration is therefore critical for the long‐term preservation of species habitat and ecosystem services, yet we have little understanding of the economic costs and benefits of doing so. Using data and simulations from Queensland, Australia, we show that the opportunity cost of preserving wetlands is likely to be much higher under sea level rise than under current sea levels. However, we find that payments for ecosystem services can alleviate these costs, and in many cases may make expanding the reserve network profitable in the long run. This highlights the need to develop markets and payment mechanisms for ecosystem services to support climate change adaptation policies for coastal wetlands.
Exploring the Permanence of Conservation Covenants
Authors: Hardy Mathew J. , Fitzsimons James A. , Bekessy Sarah A. , Gordon Ascelin
Published: March 2016

Conservation on private land is a growing part of international efforts to stem the decline of biodiversity. In many countries, private land conservation policy often supports in perpetuity covenants and easements, which are legally binding agreements used to protect biodiversity on private land by restricting activities that may negatively impact ecological values. With a view to understand the long‐term security of these mechanisms, we examined release and breach data from all 13 major covenanting programs across Australia. We report that out of 6,818 multi‐party covenants, only 8 had been released, contrasting with approximately 130 of 673 single‐party covenants. Breach data was limited, with a minimum of 71 known cases where covenant obligations had not been met. With a focus on private land conservation policy, we use the results from this case study to argue that multi‐party covenants appear an enduring conservation mechanism, highlight the important role that effective monitoring and reporting of the permanency of these agreements plays in contributing to their long‐term effectiveness, and provide recommendations for organizations seeking to improve their monitoring programs. The collection of breach and release data is important for the continuing improvement of conservation policies and practices for private land.
The clinical value of exhaled nitric oxide in patients with lung cancer
Authors: Liu Peng‐Fei , Zhao Da‐Hui , Qi Yan , Wang Jian‐Guo , Zhao Ming , Xiao Kun , Xie Li‐Xin
Published: March 2016

Introduction and Objectives

To investigate the clinical value of fractional exhaled nitric oxide (FeNO) in lung cancer patients.

Methods

A total of 172 healthy control subjects and 164 patients with histopathologically confirmed lung cancer were enrolled in this study. The FeNO measurements and pulmonary function tests were conducted in the Chinese PLA General Hospital. The recorded data included FeNO, the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), FEV1/FVC, the FEV1 (% predicted), the demographic characteristics, the presence of complications and the smoking status.

Results

The patients with lung cancer had a significantly higher level of eNO than the healthy control subjects (33.85 ± 15.63 ppb, n = 163; 16.83 ± 4.17 ppb, n = 172; P < 0.01). The areas under receiver operating characteristic curves for eNO predicting airway inflammation in lung cancer subjects and healthy control subjects was 0.932 (95% confidence interval: 0.904–0.961). In the lung cancer group, the eNO levels in the squamous cell carcinoma, adenocarcinoma, small‐cell lung cancer and lung carcinoid tumor groups were significantly different (P < 0.01). Lung cancer patients with a predicted FEV1% value <80% had a higher level of eNO than the patients with a predicted FEV1% value ≥80%.

Conclusions

The eNO levels in patients with lung cancer were higher than the normal level, especially in the patients with squamous cell carcinoma and small‐cell lung cancer. The differences in eNO among the lung cancer subtypes were statistically significant. Measuring eNO will be helpful in diagnosing airway inflammation in lung cancer and in the classification of lung cancer.
FISCAL FEDERALISM, DECENTRALIZATION, AND ECONOMIC GROWTH: A META‐ANALYSIS
Authors: Baskaran Thushyanthan , Feld Lars P. , Schnellenbach Jan
Published: March 2016

The theoretical literature on fiscal federalism has identified several channels through which government decentralization could affect economic growth. Much of the literature focuses on the efficiency aspects of a decentralized provision of public services, but decentralization may also increase growth by raising the ability of the political system to innovate and carry out reforms. In contrast, some authors argue that decentralization increases corruption and government inefficiency, and thus may diminish growth. Given this theoretical ambiguity, several studies have attempted to identify the effect of decentralization on economic growth empirically over the last two decades. We review and conduct a meta‐analysis of this empirical literature. Based on our analysis, we point out open questions and discuss possible ways to answer them. (JEL H77, O43, C52)
Emergence and accumulation of novel pathogens suppress an invasive species
Authors: Stricker Kerry Bohl , Harmon Philip F. , Goss Erica M. , Clay Keith , Luke Flory S.
Published: March 2016

Emerging pathogens are a growing threat to human health, agriculture and the diversity of ecological communities but may also help control problematic species. Here we investigated the diversity, distribution and consequences of emerging fungal pathogens infecting an aggressive invasive grass that is rapidly colonising habitats throughout the eastern USA. We document the recent emergence and accumulation over time of diverse pathogens that are members of a single fungal genus and represent multiple, recently described or undescribed species. We also show that experimental suppression of these pathogens increased host performance in the field, demonstrating the negative effects of emerging pathogens on invasive plants. Our results suggest that invasive species can facilitate pathogen emergence and amplification, raising concerns about movement of pathogens among agricultural, horticultural, and wild grasses. However, one possible benefit of pathogen accumulation is suppression of aggressive invaders over the long term, potentially abating their negative impacts on native communities.
Global patterns and substrate‐based mechanisms of the terrestrial nitrogen cycle
Authors: Niu Shuli , Classen Aimée T. , Dukes Jeffrey S. , Kardol Paul , Liu Lingli , Luo Yiqi , Rustad Lindsey , Sun Jian , Tang Jianwu , Templer Pamela H. , Thomas R. Quinn , Tian Dashuan , Vicca Sara , Wang Ying‐Ping , Xia Jianyang , Zaehle Sönke
Published: March 2016

Nitrogen (N) deposition is impacting the services that ecosystems provide to humanity. However, the mechanisms determining impacts on the N cycle are not fully understood. To explore the mechanistic underpinnings of N impacts on N cycle processes, we reviewed and synthesised recent progress in ecosystem N research through empirical studies, conceptual analysis and model simulations. Experimental and observational studies have revealed that the stimulation of plant N uptake and soil retention generally diminishes as N loading increases, while dissolved and gaseous losses of N occur at low N availability but increase exponentially and become the dominant fate of N at high loading rates. The original N saturation hypothesis emphasises sequential N saturation from plant uptake to soil retention before N losses occur. However, biogeochemical models that simulate simultaneous competition for soil N substrates by multiple processes match the observed patterns of N losses better than models based on sequential competition. To enable better prediction of terrestrial N cycle responses to N loading, we recommend that future research identifies the response functions of different N processes to substrate availability using manipulative experiments, and incorporates the measured N saturation response functions into conceptual, theoretical and quantitative analyses.
Adsorption behavior of methacryloyloxydecyl dihydrogen phosphate on an apatite surface at neutral pH
Authors: Bista Baba , Nakashima Syozi , Nikaido Toru , Sadr Alireza , Takagaki Tomohiro , Romero Maria J. R. H. , Sato Takaaki , Tagami Junji
Published: March 2016

This study aimed to quantify the adsorption affinity of neutralized 10‐methacryloyloxydecyl dihydrogen phosphate (10‐MDP‐N) toward hydroxyapatite (HA) and dicalcium phosphate dihydrate (DCPD) at pH 7.0 by employing the Langmuir isotherm model. Furthermore, the effects of inorganic phosphate (Pi) and fluoride (F−) ions on the adsorption of 10‐MDP‐N onto HA and DCPD were examined. Fixed amounts of HA and DCPD powders were suspended in different concentrations of 10‐MDP‐N solutions and were incubated for 18 h. Equilibrated concentrations of 10‐MDP‐N were measured by spectrophotometry and the adsorption affinity was estimated using the Langmuir model. Moreover, the adsorption was examined by zeta‐potential analysis. The results indicated that significant Langmuir correlation was noted in both substrates, along with an increasing negative zeta‐potential; however, in DCPD the correlation was less strong. The addition of 1.0 mM Pi slightly delayed the adsorption of 10‐MDP‐N onto both substrates, whereas 3.0 mM Pi drastically delayed adsorption onto HA but completely inhibited adsorption onto DCPD. Up to 50 ppm, F− enhanced the adsorption onto HA, and the adsorption plateaued at higher concentrations of F−, whereas no obvious influence of F− on the adsorption onto DCPD was noted.
Diagnostic dichotomy: A question of thoracic mesothelioma
Authors: May J. , Fews D. , Tennant K. , Mair T.
Published: March 2016

A 12‐year‐old Irish Sport Horse gelding was presented with a two‐day history of acute onset dyspnoea, pyrexia, tachycardia and ventral sternal oedema. A pleural effusion was identified, and thoracocentesis yielded a haemorrhagic modified transudate. Cytological examination of the fluid showed numerous red blood cells with smaller numbers of large nucleated cells that exhibited mild anisocytosis and anisokaryosis. Thoracoscopy identified adhesions between the visceral and dorsal parietal pleura, haemorrhagic effusion ventrally and haemorrhagic soft tissue plaques scattered over the diaphragm and mediastinum; biopsies of tissue on the caudal mediastinum were obtained. Histopathological examination of the biopsies identified inflammation, with a suspicion of underlying neoplasia; adenocarcinoma, haemangiosarcoma or mesothelioma were considered most likely, but could not be confirmed on the basis of these examinations. The horse was euthanased, and mesothelioma was diagnosed followingpost mortemexamination. This case demonstrates some of the difficulties associated with the accuratepremortemdiagnosis of mesothelioma.
‘Smelling’ the cerebrospinal fluid: olfactory signaling molecules are expressed in and mediate chemosensory signaling from the choroid plexus
Authors: Gonçalves Isabel , Hubbard Peter C. , Tomás Joana , Quintela Telma , Tavares Gabriela , Caria Sandra , Barreiros Daniela , Santos Cecília R.A.
Published: March 2016

The olfactory‐type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G‐protein (Gαolf), adenylate cyclase 3 and cyclic nucleotide‐gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP‐brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration‐dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gαolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C–inositol 1,4,5‐trisphosphate pathways. Olfactory‐like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.
Controls on fluid movement in crustal lithologies: evidence from zircon in metaconglomerates from Shetland
Authors: Dempster T. J. , Macdonald F.
Published: March 2016

An investigation of the morphology of zircon in clasts and matrix of a greenschist facies metaconglomerate from Shetland has revealed a history of alteration of radiation‐damaged grains, partial dissolution and growth of new zircon. These processes are linked to the generation of chemically modified dark backscattered electron (BSE) zircon that is spatially related to fractures generated during radiation damage; embayments and rounding of zircon margins; and late overgrowths of original grains. These late modifications of zircon are all linked to the presence of fluids and so zircon morphology is used to track fluid behaviour in different lithologies in the metaconglomerate. Alteration is unrelated to clast margins and radically different in various clast types. This reflects a difference in permeability and suggests that deformation strongly controls fluid influx into quartzite, whereas zircon alteration in granite is associated with a restricted permeability reflecting the more limited response to deformation events.
Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study
Authors: Liu Jun , Pan Yu , Chen Lei , Qiao Qing Yan , Wang Jing , Pan Li Hua , Gu Yan Hong , Gu Hui Fang , Fu Shun Kun , Jin Hui Min
Published: March 2016

Introduction Aspirin is an effective antiplatelet drug for preventing cardiovascular events in high‐risk subjects. However, for patients with chronic kidney disease and undergoing hemodialysis (HD), its preventive efficacy remains controversial. The present study aimed to determine whether aspirin therapy reduces the risk of cardiovascular disease (CVD) and all‐cause mortality in patients on HD.

Methods We conducted a 5‐y prospective cohort study involving patients on HD. Major exposure variables included prescription of aspirin (100 mg/d) and no aspirin (nonaspirin). The primary outcomes included all‐cause death, cardiovascular events, hemorrhage, and ischemic stroke. The secondary outcome included bleeding events defined by the requirement of hospitalization.

Findings In this study, 406 patients on regular HD were involved during a 5‐y follow‐up. Among these, 152 and 254 propensity‐matched patients were enrolled in the aspirin and nonaspirin cohort, respectively. The cumulative survival rate was not significantly higher in the aspirin than in the nonaspirin users (log rank χ2 = 1.080, P = 0.299). Aspirin use was not significantly associated with reduced all‐cause mortality, fatal and nonfatal congestive heart failure, as well as acute myocardial infarction and ischemic stroke. The risk of fatal cerebral hemorrhage was not significantly increased in the aspirin users (HR = 1.795, 95% CI 0.666–4.841, P = 0.174). After adjustment for other confounders, aspirin use was also not associated with decreased risk of all‐cause mortality and CVD.

Discussion The present prospective cohort study suggests that low‐dose aspirin use is not associated with a significant decrease in the risks of all‐cause mortality, CVD, and stroke in population undergoing HD (ClinicalTrials.gov number, NCT02261025).
Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b
Authors: Tamori Akihiro , Yoshida Kanako , Kurai Osamu , Kioka Kiyohide , Hai Hoang , Kozuka Ritsuzo , Motoyama Hiroyuki , Kawamura Etsushi , Hagihara Atsushi , Uchida‐Kobayashi Sawako , Morikawa Hiroyasu , Enomoto Masaru , Murakami Yoshiki , Kawada Norifumi
Published: March 2016

Simeprevir (SMV) is a potent, macrocyclic hepatitis C virus (HCV) non‐structural 3/4 A protease inhibitor. This prospective study compared the efficacy and safety of SMV in combination with peginterferon α2a + ribavirin (P2aR) and with peginterferon α2b + ribavirin (P2bR) in Japanese patients with HCV genotype 1b infection.

Methods

Hepatitis C virus genotype 1b patients were randomly assigned to receive SMV (100 mg QD) with P2aR for 12 weeks, then P2aR alone for 12 or 36 weeks; or SMV (100 mg QD) with P2bR for 12 weeks, then P2bR alone for 12 or 36 weeks. The primary endpoint was a sustained virologic response 24 weeks after completing treatment (SVR24).

Results

In total, 151 patients were randomly assigned to the P2aR (n = 76) or P2bR group (n = 75). Six patients dropped out. Sustained virologic response 24 weeks after completing treatment was achieved in 55 (75.3%) of 73 P2aR patients and 55 (76.4%) of 72 P2bR patients. There was no difference in the rate of SVR24 between the two groups (P = 0.88). No differences in the proportion of patients who became HCV RNA‐negative were detected between the P2aR and P2bR groups. The two groups had comparable numbers of adverse events, which led to the discontinuation of treatment in 9.6% and 8.3% of participants in the P2aR and P2bR groups, respectively.

Conclusion

Peginterferon α2a or α2b in combination with SMV + ribavirin therapy showed identical antiviral effects in patients with chronic hepatitis C. Also, the incidence of adverse events was identical for both regimens.
Hepatitis B virus vaccination‐related seroprevalence among health‐care personnel in a Japanese tertiary medical center
Authors: Yanase Mikio , Murata Kazumoto , Mikami Shintaro , Nozaki Yuichi , Masaki Naohiko , Mizokami Masashi
Published: March 2016

Aim

Few studies concerning the protective management of hepatitis B virus (HBV) infection among health‐care personnel (HCP), excluding occult HBV or carriers, have been reported. Therefore, we undertook a cross‐sectional study of the updated status of HBV vaccine management by measuring the antibody to hepatitis B surface antigen (anti‐HBs) along with the antibody to hepatitis B core antigen (anti‐HBc).

Methods

Both anti‐HBs and anti‐HBc were assessed in 1085 HCP employed by our institute. Hepatitis B virus vaccination‐related histories were recorded using self‐administered questionnaires.

Results

Of 1085 HCP, 27 (2.5%) were positive for anti‐HBc, and its positive rate increased with age. Of the 1058 subjects with negative anti‐HBc, 879 (83.1%) were positive for anti‐HBs. The median titer of anti‐HBs was 71.1 mIU/mL, which was higher in female subjects (P = 0.037). By age group, the positive rate of anti‐HBs were 77.5%, 89.3%, 90.8%, and 81.6% in the groups aged ≤29, 30–39, 40–49, and ≥50 years, respectively (P < 0.001). Of the 908 subjects who reported receiving HBV vaccination, 6 (0.7%) were positive for anti‐HBc. Among them, one subject was suspected to have a possible subclinical HBV infection after the HBV vaccination.

Conclusion

We report the current HBV vaccination‐related seroprevalence of anti‐HBs along with anti‐HBc in a Japanese tertiary medical institution consisting of more than 1000 HCP, which was an level comparable to similar sized hospitals in developed countries. Anti‐HBc would be important for understanding HBV status, but not necessary for general HBV vaccine management for HCP.
A quality assessment of randomized controlled trial reports in endodontics
Authors: Lucena C. , Souza E. M. , Voinea G. C. , Pulgar R. , Valderrama M. J. , De‐Deus G.
Published: March 2016

Aim

To assess the quality of the randomized clinical trial (RCT) reports published in Endodontics between 1997 and 2012.

Methodology

Retrieval of RCTs in Endodontics was based on a search of the Thomson Reuters Web of Science (WoS) database (March 2013). Quality evaluation was performed using a checklist based on the Jadad criteria, CONSORT (Consolidated Standards of Reporting Trials) statement and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). Descriptive statistics were used for frequency distribution of data. Student's t‐test and Welch test were used to identify the influence of certain trial characteristics upon report quality (α = 0.05).

Results

A total of 89 RCTs were evaluated, and several methodological flaws were found: only 45% had random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, and 19% were nonblinded designs. Regarding statistics, only 55% of the RCTs performed adequate sample size estimations, only 16% presented confidence intervals, and 25% did not provide the exact P‐value. Also, 2% of the articles used no statistical tests, and in 87% of the RCTs, the information provided was insufficient to determine whether the statistical methodology applied was appropriate or not. Significantly higher scores were observed for multicentre trials (P = 0.023), RCTs signed by more than 5 authors (P = 0.03), articles belonging to journals ranked above the JCR median (P = 0.03), and articles complying with the CONSORT guidelines (P = 0.000).

Conclusions

The quality of RCT reports in key areas for internal validity of the study was poor. Several measures, such as compliance with the CONSORT guidelines, are important in order to raise the quality of RCTs in Endodontics.
Different in vitro proliferation and cytokine‐production inhibition of memory T‐cell subsets after calcineurin and mammalian target of rapamycin inhibitors treatment
Authors: Merino David , San Segundo David , Medina Juan M. , Rodrigo Emilio , Asensio Esther , Irure Juan , Fernández‐Fresnedo Gema , Arias Manuel A. , López‐Hoyos Marcos
Published: March 2016

Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi) are the main immunosuppressants used for long‐term maintenance therapy in transplant recipients to avoid acute rejection episodes. Both groups of immunosuppressants have wide effects and are focused against the T cells, although different impacts on specific T‐cell subsets, such as regulatory T cells, have been demonstrated. A greater knowledge of the impact of immunosuppression on the cellular components involved in allograft rejection could facilitate decisions for individualized immunosuppression when an acute rejection event is suspected. Memory T cells have recently gained focus because they might induce a more potent response compared with naive cells. The impact of immunosuppressants on different memory T‐cell subsets remains unclear. In the present study, we have studied the specific impact of CNI (tacrolimus) and mTORi (rapamycin and everolimus) over memory and naive CD4+ T cells. To do so, we have analysed the proliferation, phenotypic changes and cytokine synthesis in vitro in the presence of these immunosuppressants. The present work shows a more potent effect of CNI on proliferation and cytokine production in naive and memory T cells. However, the mTORi permit the differentiation of naive T cells to the memory phenotype and allow the production of interleukin‐2. Taken together, our data show evidence to support the combined use of CNI and mTORi in transplant immunosuppression.
High‐Energy Mechanical Treatment Boosts Ion Transport in Nanocrystalline Li2B4O7
Authors: Wohlmuth Dominik , Epp Viktor , Stanje Bernhard , Welsch Anna‐Maria , Behrens Harald , Wilkening Martin
Published: March 2016

In many cases fast solid ion conductors are characterized by a large number fraction of defects and vacant positions that enable the ions to move over long distances in a facile way. The introduction of structural disorder via high‐energy mechanical impact represents a very promising possibility to improve and to tune the transport properties of otherwise poorly conducting solids. Lithium tetraborate, Li2B4O7, in its single crystalline form or with an average crystallite size in the μm range, is known as a very poor Li ion conductor and can serve as a model compound to study the influence of structural disorder on ion dynamics. In the present study, we used high‐energy ball milling to prepare nanocrystalline defect‐rich Li2B4O7 characterized by a mean crystallite diameter of ca. 20 nm. With increasing milling time the sample became partly amorphous. Polycrystalline Li2B4O7 with crystallite sizes in the order of 100 nm served as starting material. The nanostructured samples obtained show dc conductivities σdc in the order of 2.5 × 10−7 S/cm at 490 K which represents an increase by more than four orders of magnitude compared to the source material. While conductivity spectroscopy was applied to study the effect of different milling times on ionic conductivity in detail; Li ion self‐diffusion in nanostructured Li2B4O7 as well as in the starting material was investigated by variable‐temperature solid‐state 7Li nuclear magnetic resonance (NMR) relaxometry. While the first is sensitive to long‐range ion transport, lithium NMR is able to access also short‐ranged ion motions.
Crack‐Free Drying of Ceramic Microparts on a Hydrophobic Flexible Polymer Substrate Using Soft Lithography
Authors: Su Bo , Meng Junhu , Zhang Zhaozhu
Published: March 2016

Drying is a critical step in the fabrication of ceramic microparts from suspensions using soft lithography. In this communication, a simple method using a hydrophobic flexible polymer substrate was demonstrated to avoid the formation of cracks within ceramic microparts. Crack‐free alumina green microchannel parts with 120 μm feature size were attained on a polyethylene film. The results show that both the hydrophobic and flexible properties of the polymeric substrates can remove the substrate constraint to the green body of micropart, which is capable of preventing cracks formation. The method can be used to fabricate ceramic microparts/micropatterns for microeletromechanical systems and functional thick ceramic films.
Polyamorphism in Aluminum Nitride: A First Principles Molecular Dynamics Study
Authors: Durandurdu Murat
Published: March 2016

The high‐pressure behavior of amorphous aluminum nitride is investigated for the first time by means of ab initio molecular dynamics simulations. It is found to undergo two successive first‐order phase transformations with the application of pressure. The first one is a polyamorphic phase transition in which the low‐density amorphous phase transforms into a high‐density amorphous phase having an average coordination number of about 4.6. The high‐density amorphous structure transforms back to a low‐coordinated amorphous network upon pressure release but its density is higher than that of the original low‐density amorphous phase. The second phase change is the crystallization of the high‐density amorphous state into a rocksalt structure. A careful analysis suggests that the hexagonal‐like nanoclusters presented in amorphous aluminum nitride prevent the formation of a very dense amorphous phase (about sixfold coordinated) during the first phase transition and they act as a nucleation center for the crystallization process.
Management of Lead Content for Growth of {001}‐Oriented Lead Magnesium Niobate‐Lead Titanate Thin Films
Authors: Keech Ryan , Shetty Smitha , Wang Ke , Trolier‐McKinstry Susan
Published: March 2016

A scalable growth process for domain engineered {001}‐oriented lead magnesium niobate—lead titanate (PMN‐PT) thin films with Lotgering factors of 0.98–1.0, without an orienting perovskite seed layer, is presented. Deposition of a 2–3‐nm‐thick PbO buffer layer on {111} Pt thin film bottom electrodes, prior to chemical solution deposition of PMN‐PT reduces the driving force for Pb diffusion from the PMN‐PT to the bottom electrode, and facilitates nucleation of {001}‐oriented perovskite grains. Energy dispersive spectroscopy demonstrated that up to 10% of the Pb from a PMN‐PT precursor solution may diffuse into the bottom electrode. PMN‐PT grains with a mixed {101}/{111} orientation in a matrix of Pb‐deficient pyrochlore phase were then promoted near the interface. When this is prevented, phase‐pure films with {001} orientation can be achieved.
The accuracy and acceptability of performing capillary blood glucose measurements at the earlobe
Authors: Chan Helen Y.L. , Lau Tracy S.L. , Ho S.Y. , Leung Doris Y.P. , Lee Diana T.F.
Published: March 2016

Aims

To examine the accuracy and acceptability of capillary blood glucose monitoring using the earlobe.

Background

In current practice, blood samples for capillary blood glucose monitoring are obtained from the fingertip. Because obtaining blood samples from the fingertip is sometimes contraindicated, it is necessary to identify an alternative site for the procedure.

Design

A single‐patient design with repeated measurements.

Methods

Patients from an outpatient clinic and four medical wards were recruited to the study, in 2014, if they met one of the following criteria: (i) were in a relatively stable glycaemic state; (ii) were currently receiving intravenous infusion; (iii) had been diagnosed with chronic renal impairment or (iv) were aged 65 years or above and bedbound. Blood samples were obtained from the fingertip and the earlobe consecutively for blood glucose monitoring. Participants were asked to rate the respective pain level caused by the procedures. Intra‐class correlation coefficient was calculated to demonstrate the level of absolute agreement between the two blood glucose readings. The Wilcoxon signed rank test was used to compare the pain levels.

Results

A total of 120 patients participated in the study between February – December 2014. The intra‐class correlation coefficient between the readings at the two sampling sites was significantly high, except in a hypoglycaemic state. Participants generally reported a significantly lower level of pain when the earlobe rather than fingertip was pricked.

Conclusion

The earlobe is to be recommended as a safe alternative site for capillary blood glucose monitoring unless the patient is in a suspected hypoglycaemic state.
Renal Function Alters Antihypertensive Regimens in Type 2 Diabetic Patients
Authors: Weinrauch Larry A. , Bayliss George , Segal Alissa R. , Liu Jiankang , Wisniewski Eric , D'Elia John A.
Published: March 2016

To determine the prevalence of multidrug antihypertensive therapy (MDAT), records were evaluated for patients with both type 2 diabetes and hypertension during a 5‐year period at Joslin Diabetes Center. Hypertension control was defined as requiring multiple drugs if three or more antihypertensive drugs were used, one of which must be a diuretic (unless patient is receiving dialysis), or use of four or more antihypertensive drugs, one of which a diuretic (unless patient is receiving dialysis) was established. The objective was to determine the prevalence of multidrug requirement for hypertensive therapy in relationship to four levels of renal function estimated by the Modification of Diet in Renal Disease formula for glomerular filtration rate (GFR). Among 10,151 patients, mean estimated GFR was 80 mL/min. Using standard (ASN) classification for renal function, we noted the following breakdown of MDAT use:

Estimated GFR
Drugs, Mean No.
≥3 Drugs, No. (%)
≥4 Drugs, No. (%)

<30
3.1
379 (67)
214 (38)

30–60
2.7
1233 (55)
538 (24)

60–90
2.0
1279 (33)
458 (12)

>90
1.5
600 (17)
185 (5)

Prevalence of multidrug antihypertensive therapy is markedly increased in the presence of reduced renal function.
Atopic dermatitis induces the expansion of thymus‐derived regulatory T cells exhibiting a Th2‐like phenotype in mice
Authors: Moosbrugger‐Martinz Verena , Tripp Christoph H. , Clausen Björn E. , Schmuth Matthias , Dubrac Sandrine
Published: March 2016

Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper‐responsiveness of the skin and environmental factors. Although the important role of abnormal immune reactivity in the pathogenesis of AD is widely accepted, the role of regulatory T cells (Tregs) remains elusive. We found that the Treg population is expanded in a mouse model of AD, i.e. mice topically treated with vitamin D3 (VitD). Moreover, mice with AD‐like symptoms exhibit increased inducible T‐cell costimulator (ICOS)‐, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4)‐ and Glycoprotein‐A repetitions predominant receptor (GARP)‐expressing Tregs in skin‐draining lymph nodes. Importantly, the differentiation of Tregs into thymus‐derived Tregs is favoured in our mouse model of AD. Emigrated skin‐derived dendritic cells are required for Treg induction and Langerhans cells are responsible for the biased expansion of thymus‐derived Tregs. Intriguingly, thymus‐derived Tregs isolated from mice with AD‐like symptoms exhibit a Th2 cytokine profile. Thus, AD might favour the expansion of pathogenic Tregs able to produce Th2 cytokines and to promote the disease instead of alleviating symptoms.
Skin cancer in patients with psoriasis
Authors: Egeberg A. , Thyssen J.P. , Gislason G.H. , Skov L.
Published: March 2016

Background

Psoriasis is a chronic inflammatory skin disease that is commonly treated with ultraviolet phototherapy and systemic immunosuppressant drugs, which may confer a risk of skin cancer. Previous studies on the risk of skin cancer in patients with psoriasis have shown conflicting results.

Objectives

We investigated the risk of new‐onset melanoma and non‐melanoma skin cancer (NMSC), respectively, in a large cohort of patients with psoriasis and psoriatic arthritis.

Methods

Data on all Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2012 were linked at individual‐level in nationwide registers. Incidence rates per 10 000 person‐years were calculated, and incidence rate ratios (IRRs) were estimated by Poisson regression models.

Results

The study comprised 5 559 420 individuals with a maximum follow‐up time of 16 years. There were 75 410 patients with psoriasis, and 25 087 and 58 051 individuals developed melanoma and NMSC, respectively, during follow‐up. Adjusted IRRs (95% CI) of melanoma were 1.19 (1.03–1.37), 1.09 (0.75–1.58) and 1.36 (0.94–1.99), in mild psoriasis, severe psoriasis and psoriatic arthritis, respectively, and the corresponding adjusted IRRs of NMSC were 1.67 (1.55–1.81), 1.32 (1.10–1.59) and 1.62 (1.27–2.05) respectively.

Conclusions

We observed a modestly increased risk of melanoma and NMSC in patients with mild psoriasis, whereas patients with severe psoriasis and psoriatic arthritis had increased risk of NMSC but not melanoma. While the risk of skin cancer is only modestly increased in patients with psoriasis, clinicians should remain vigilant.