bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Effects of a Pharmacist Intervention in Acute Wards – A Randomized Controlled Trial
Authors: Nielsen Trine R. H. , Honoré Per H. , Rasmussen Mette , Andersen Stig E.
Published: April 2017

The purpose of the study was to investigate the clinical effect of a clinical pharmacist (CP) intervention upon admission to hospital on inpatient harm and to assess a potential educational bias. Over 16 months, 593 adult patients taking ≥4 medications daily were included from three Danish acute medicine wards. Patients were randomized to either the CP intervention or the usual care (prospective control). To assess a potential educational bias, a retrospective control group was formed by randomization. The CP intervention comprised medication history, medication reconciliation, medication review and entry of proposed prescriptions into the electronic prescribing system. The primary outcome of inpatient harm was identified using triggers from the Institute of Healthcare Improvement Global Trigger Tool. Harms were validated and rated for severity by two independent and blinded outcome panels. Secondary end‐points were harms per patient, length of hospital stay, readmissions and 1‐year mortality. Harm affected 11% of the patients in the intervention group compared to 17% in the combined control group, odds ratio (OR) 0.57 (CI 0.32–1.02, p = 0.06). The incidence of harm was similar in the intervention and prospective control groups, OR 0.80 (CI 0.40–1.59, p = 0.52) but occurred less frequently in the intervention than in the retrospective control group OR 0.46 (CI 0.25–0.85, p = 0.01). An educational bias from the intervention to the control group might have contributed to this negative outcome. In conclusion, the CP intervention at admission to hospital had no statistically significant effect on inpatient harm.
Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma: a Children's Oncology Group report
Authors: Lee Sanghoon , Day Nancy S. , Miles Rodney R. , Perkins Sherrie L. , Lim Megan S. , Ayello Janet , van de Ven Carmella , Harrison Lauren , El‐Mallawany Nader K. , Goldman Stanton , Cairo Mitchell S.
Published: May 2017

Burkitt lymphoma (BL) is the most common histological subtype of non‐Hodgkin lymphoma (NHL) in children and adolescents. Through the introduction of short intensive multi‐agent chemoimmunotherapy, survival has improved significantly over the past 30 years. However, this successful approach is limited by significant chemotherapy‐induced acute toxicity and risk of developing resistant disease, demonstrating the need to identify less toxic and targeted therapies. We analysed the comparative genomic signature and targetable signalling pathways in paediatric BL (PEBL) samples from the Children's Oncology Group study (ANHL01P1) by genomic profiling and selected genes were confirmed by quantitative real time polymerase chain reaction. These results were compared to PEBL samples from public databases and utilised the Gene Expression Omnibus (GEO) Series (GSE) 10172 and 4475 (n = 16), and 4732 (n = 15). Three hundred and seventy‐six genes (approximately 25%) were similarly expressed among three PEBL sample groups. Several target genes in Toll‐like receptor signalling, JAK‐STAT signalling and MAPK signalling were significantly overexpressed in PEBL. In addition, several tyrosine kinases, including Bruton tyrosine kinase, protein tyrosine phosphatase and histone deacetylase inhibitor were highly expressed in PEBL. These pre‐clinical results suggest that specific signal transduction pathways are overly expressed in PEBL and several pathways could serve as potential future therapeutic targets.
Modelling individual response time effects between and within experimental speed conditions: A GLMM approach for speeded tests
Authors: Goldhammer Frank , Steinwascher Merle A. , Kroehne Ulf , Naumann Johannes
Published: May 2017

Completing test items under multiple speed conditions avoids the performance measure being confounded with individual differences in the speed–accuracy compromise, and offers insights into the response process, that is, how response time relates to the probability of a correct response. This relation is traditionally represented by two conceptually different functions: the speed‐accuracy trade‐off function (SATF) across conditions relating the condition average response time to the condition average of accuracy, and the conditional accuracy function (CAF) within a condition describing accuracy conditional on response time. Using a generalized linear mixed modelling approach, we propose an item response modelling framework that is suitable for item response and response time data from experimental speed conditions. The proposed SATF and CAF model accommodates response time effects between conditions (i.e., person and item SATF slope) and within conditions (i.e., residual CAF slopes), captures person and item differences in these effects, and is suitable for measures with a strong speed component. Moreover, for a single condition a CAF model is proposed distinguishing person, item and residual CAF. The properties of the models are illustrated with an empirical example.
Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N‐arachidonoylphosphatidylethanolamine
Authors: Nerandzic Vladimir , Mrozkova Petra , Adamek Pavel , Spicarova Diana , Nagy Istvan , Palecek Jiri
Published: May 2017

Background and Purpose

Endocannabinoids play an important role in modulating spinal nociceptive signalling, crucial for the development of pain. The cannabinoid CB1 receptor and the TRPV1 cation channel are both activated by the endocannabinoid anandamide, a product of biosynthesis from the endogenous lipid precursor N‐arachidonoylphosphatidylethanolamine (20:4‐NAPE). Here, we report CB1 receptor‐ and TRPV1‐mediated effects of 20:4‐NAPE on spinal synaptic transmission in control and inflammatory conditions.

Experimental Approach

Spontaneous (sEPSCs) and dorsal root stimulation‐evoked (eEPSCs) excitatory postsynaptic currents from superficial dorsal horn neurons in rat spinal cord slices were assessed. Peripheral inflammation was induced by carrageenan. Anandamide concentration was assessed by mass spectrometry.

Key Results

Application of 20:4‐NAPE increased anandamide concentration in vitro. 20:4‐NAPE (20 μM) decreased sEPSCs frequency and eEPSCs amplitude in control and inflammatory conditions. The inhibitory effect of 20:4‐NAPE was sensitive to CB1 receptor antagonist PF514273 (0.2 μM) in both conditions, but to the TRPV1 antagonist SB366791 (10 μM) only after inflammation. After inflammation, 20:4‐NAPE increased sEPSCs frequency in the presence of PF514273 and this increase was blocked by SB366791.

Conclusions and Implications

While 20:4‐NAPE treatment inhibited the excitatory synaptic transmission in both naive and inflammatory conditions, peripheral inflammation altered the underlying mechanisms. Our data indicate that 20:4‐NAPE application induced mainly CB1 receptor‐mediated inhibitory effects in naive animals while TRPV1‐mediated mechanisms were also involved after inflammation. Increasing anandamide levels for analgesic purposes by applying substrate for its local synthesis may be more effective than systemic anandamide application or inhibition of its degradation.

Linked Articles

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
Impact of MET inhibition on small‐cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway
Authors: Taniguchi Hirokazu , Yamada Tadaaki , Takeuchi Shinji , Arai Sachiko , Fukuda Koji , Sakamoto Shuichi , Kawada Manabu , Yamaguchi Hiroyuki , Mukae Hiroshi , Yano Seiji
Published: May 2017

Small‐cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Hence, novel therapeutic strategies for the treatment of SCLC are urgently required. Accordingly, several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome. The receptor tyrosine kinase MET is a receptor for hepatocyte growth factor (HGF), and aberrant activation of HGF/MET signaling is known as one of the crucial mechanisms enabling cancer progression and invasion. Here, we found that the HGF/MET signaling was aberrantly activated in chemoresistant or chemorelapsed SCLC cell lines (SBC‐5, DMS273, and DMS273‐G3H) by the secretion of HGF and/or MET copy number gain. A cell‐based in vitro assay revealed that HGF/MET inhibition, induced either by MET inhibitors (crizotinib and golvatinib), or by siRNA‐mediated knockdown of HGF or MET, constrained growth of chemoresistant SCLC cells through the inhibition of ERK and AKT signals. Furthermore, treatment with either crizotinib or golvatinib suppressed the systemic metastasis of SBC‐5 cell tumors in natural killer cell‐depleted SCID mice, predominantly through cell cycle arrest. These findings reveal the therapeutic potential of targeting the HGF/MET pathway for inhibition, to constrain tumor progression of SCLC cells showing aberrant activation of HGF/MET signaling. We suggest that it would be clinically valuable to further investigate HGF/MET‐mediated signaling in SCLC cells.
CLDN8, an androgen‐regulated gene, promotes prostate cancer cell proliferation and migration
Authors: Ashikari Daisaku , Takayama Ken‐ichi , Obinata Daisuke , Takahashi Satoru , Inoue Satoshi
Published: May 2017

The proliferation of prostate cancer cells is controlled by the androgen receptor (AR) signaling pathway. However, the function of AR target genes has not been fully elucidated. In previous studies, we have identified global AR binding sites and AR target genes in prostate cancer cells. Here, we focused on Claudin 8 (CLDN8), a protein constituting tight junctions in cell membranes. We found one AR binding site in the promoter region and two functional androgen‐responsive elements in the sequence. Reporter assay revealed that transcriptional activation of the CLDN8 promoter by androgen is dependent on these androgen‐responsive elements. Furthermore, CLDN8 mRNA is induced by androgen time‐dependently and the induction is blocked by AR inhibitor, suggesting that AR is involved in the transcriptional activation. In addition, our functional analyses by overexpression and knockdown of CLDN8 mRNA indicate that CLDN8 promotes prostate cancer cell proliferation and migration. Claudin 8 was overexpressed in prostate cancer clinical samples compared to benign tissues. Furthermore, we found that CLDN8 regulates intracellular signal transduction and stabilizes the cytoskeleton. Taken together, these results indicate that CLDN8 functions as an AR downstream signal to facilitate the progression of prostate cancer. Claudin 8 may be a novel molecular target for prostate cancer therapy.
ATP‐P2Y2‐β‐catenin axis promotes cell invasion in breast cancer cells
Authors: Zhang Jiang‐Lan , Liu Ying , Yang Hui , Zhang Hong‐Quan , Tian Xin‐Xia , Fang Wei‐Gang
Published: May 2017

Extracellular adenosine 5′‐triphosphate (ATP), secreted by living cancer cells or released by necrotic tumor cells, plays an important role in tumor invasion and metastasis. Our previous study demonstrated that ATP treatment in vitro could promote invasion in human prostate cancer cells via P2Y2, a preferred receptor for ATP, by enhancing EMT process. However, the pro‐invasion mechanisms of ATP and P2Y2 are still poorly studied in breast cancer. In this study, we found that P2Y2 was highly expressed in breast cancer cells and associated with human breast cancer metastasis. ATP could promote the in vitro invasion of breast cancer cells and enhance the expression of β‐catenin as well as its downstream target genes CD44, c‐Myc and cyclin D1, while P2Y2 knockdown attenuated above ATP‐driven events in vitro and in vivo. Furthermore, iCRT14, a β‐catenin/TCF complex inhibitor, could also suppress ATP‐driven migration and invasion in vitro. These results suggest that ATP promoted breast cancer cell invasion via P2Y2‐β‐catenin axis. Thus blockade of the ATP‐P2Y2‐β‐catenin axis could suppress the invasive and metastatic potential of breast cancer cells and may serve as potential targets for therapeutic interventions of breast cancer.
New insights into antidiabetic drugs: Possible applications in cancer treatment
Authors: Shafiei‐Irannejad Vahid , Samadi Nasser , Salehi Roya , Yousefi Bahman , Zarghami Nosratollah
Published: April 2017

Globally at 2014, it was estimated that there was 347 million people with diabetes in which 90 percent of them were diagnosed with type 2 diabetes mellitus (T2DM). Although the association between diabetes mellitus and cancer risk was found about 100 years ago, the issue is not still clear. Many studies especially cohort and case–control studies have suggested a higher risk of cancer in patients with diabetes mainly in those with type 2 diabetes. Insulin concentration is high in these patients, and due to its mitogenic effects, it may be a possible hypotheses for higher risk of cancer in diabetic patients. Therefore, antidiabetic drugs, which are involved in insulin secretion and sensitivity, may have beneficial effects in cancer treatment. Several groups of drugs with different mechanisms of action, mostly prescribed orally, are used for the treatment of type 2 diabetes mellitus including, insulin sensitizers (thiazolidinediones), insulin secretagogues (sulfonylureas), and biguanides. In this review, the possible effects of antidiabetic drugs (biguanides, thiazolidinediones, and sulfonylureas) and some of their mechanisms for overcoming cancer will be discussed.
Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target
Authors: Al‐Khami A. A. , Ghonim M. A. , Del Valle L. , Ibba S. V. , Zheng L. , Pyakurel K. , Okpechi S. C. , Garay J. , Wyczechowska D. , Sanchez‐Pino M. D. , Rodriguez P. C. , Boulares A. H. , Ochoa A. C.
Published: April 2017

Background

Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up‐regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid‐derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology.

Objective

We tested whether FAO might play a role in the development of asthma‐like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach.

Methods

OVA‐ and house dust mite (HDM)‐induced murine asthma models were used in this study.

Results

Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen‐induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma.

Conclusions and clinical relevance

These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re‐purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.
Intrinsic Light Field Images
Authors: Garces Elena , Echevarria Jose I. , Zhang Wen , Wu Hongzhi , Zhou Kun , Gutierrez Diego
Published: May 2017

We present a method to automatically decompose a light field into its intrinsic shading and albedo components. Contrary to previous work targeted to two‐dimensional (2D) single images and videos, a light field is a 4D structure that captures non‐integrated incoming radiance over a discrete angular domain. This higher dimensionality of the problem renders previous state‐of‐the‐art algorithms impractical either due to their cost of processing a single 2D slice, or their inability to enforce proper coherence in additional dimensions. We propose a new decomposition algorithm that jointly optimizes the whole light field data for proper angular coherence. For efficiency, we extend Retinex theory, working on the gradient domain, where new albedo and occlusion terms are introduced. Results show that our method provides 4D intrinsic decompositions difficult to achieve with previous state‐of‐the‐art algorithms. We further provide a comprehensive analysis and comparisons with existing intrinsic image/video decomposition methods on light field images.
The rise of glyphosate and new opportunities for biosentinel early‐warning studies
Authors: Kissane Zoe , Shephard Jill M.
Published: May 2017

Glyphosate has become the most commonly used herbicide worldwide and is reputedly environmentally benign, nontoxic, and safe for use near wildlife and humans. However, studies indicate its toxicity is underestimated and its persistence in the environment is greater than once thought. Its actions as a neurotoxin and endocrine disruptor indicate its potential to act in similar ways to persistent organic pollutants such as the organochlorines dichlorodiphenyltrichloroethane (DDT) and dioxin. Exposure to glyphosate and glyphosate‐based herbicides for both wildlife and people is likely to be chronic and at sublethal levels, with multiple and ongoing exposure events occurring in urban and agricultural landscapes. Despite this, there has been little research on the impact of glyphosate on wildlife populations, and existing studies appear in the agricultural, toxicology, and water‐chemistry literature that may have limited visibility among wildlife biologists. These studies clearly demonstrate a link between chronic exposure and neurotoxicity, endocrine disruption, cell damage, and immune suppression. There is a strong case for the recognition of glyphosate as an emerging organic contaminant and substantial potential exists for collaborative research among ecologists, toxicologists, and chemists to quantify the impact of glyphosate on wildlife and to evaluate the role of biosentinel species in a preemptive move to mitigate downstream impacts on people. There is scope to develop a decision framework to aid the choice of species to biomonitor and analysis methods based on the target contaminant, spatial and temporal extent of contamination, and perceived risk. Birds in particular offer considerable potential in this role because they span agricultural and urban environments, coastal, inland, and wetland ecosystems where glyphosate residues are known to be present.
Decisional conflict between treatment options among end‐stage renal disease patients evaluated for kidney transplantation
Authors: McPherson Laura , Basu Mohua , Gander Jennifer , Pastan Stephen O. , Mohan Sumit , Wolf Michael S. , Chiles Mariana , Russell Allison , Lipford Kristie , Patzer Rachel E.
Published: April 2017

Although kidney transplantation provides a significant benefit over dialysis, many patients with end‐stage renal disease (ESRD) are conflicted about their decision to undergo kidney transplant. We aimed to identify the prevalence and characteristics associated with decisional conflict between treatment options in ESRD patients presenting for transplant evaluation. Among a cross‐sectional sample of patients with ESRD (n=464) surveyed in 2014 and 2015, we assessed decisional conflict through a validated 10‐item questionnaire. Decisional conflict was dichotomized into no decisional conflict (score=0) and any decisional conflict (score>0). We investigated potential characteristics of patients with decisional conflict using bivariate and multivariable logistic regression. The overall mean age was 50.6 years, with 62% male patients and 48% African American patients. Nearly half (48.5%) of patients had decisional conflict regarding treatment options. Characteristics significantly associated with decisional conflict in multivariable analysis included male sex, lower educational attainment, and less transplant knowledge. Understanding characteristics associated with decisional conflict in patients with ESRD could help identify patients who may benefit from targeted interventions to help patients make informed, value‐based, and supported decisions when deciding how to best treat their kidney disease.
Unusual dimerization of a BcCsp mutant leads to reduced conformational dynamics
Authors: Carvajal Alonso I. , Vallejos Gabriel , Komives Elizabeth A. , Castro‐Fernández Víctor , Leonardo Diego A. , Garratt Richard C. , Ramírez‐Sarmiento César A. , Babul Jorge
Published: April 2017

Cold shock proteins (Csp) constitute a family of ubiquitous small proteins that act as RNA‐chaperones to avoid cold‐induced termination of translation. All members contain two subdomains composed of 2 and 3 β‐strands, respectively, which are connected by a hinge loop and fold into a β‐barrel. Bacillus caldolyticus Csp (BcCsp) is one of the most studied members of the family in terms of its folding, function, and structure. This protein has been described as a monomer in solution, although a recent crystal structure showed dimerization via domain swapping (DS). In contrast, other cold shock proteins of the same fold are known to dimerize in a nonswapped arrangement. Hypothesizing that reducing the size of the hinge loop may promote swapping as in several other DS proteins with different folds we deleted two residues from these region (BcCsp∆36‐37), leading to a protein in monomer–dimer equilibrium with similar folding stability to that of the wild‐type. Strikingly, the crystal structure of BcCsp∆36‐37 revealed a nonswapped dimer with its interface located at the nucleic acid‐binding surface, showing that the deletion led to structural consequences far from the perturbation site. Concomitantly, circular dichroism experiments on BcCsp∆36‐37 demonstrated that binding of the oligonucleotide hexathymidine disrupts the dimer. Additionally, HDXMS shows a protective effect on the protein structure upon dimerization, where the resulting interactions between ligand‐binding surfaces in the dimer reduced the extent of exchange throughout the whole protein. Our work provides evidence of the complex interplay between conformational dynamics, deletions, and oligomerization within the Csp protein family.

Databases

Structural data are available in the Protein Data Bank under accession number 5JX4.
Virus–host interplay in hepatitis B virus infection and epigenetic treatment strategies
Authors: Hensel Kai O. , Rendon Julio C. , Navas Maria‐Cristina , Rots Marianne G. , Postberg Jan
Published: April 2017

Worldwide, chronic hepatitis B virus (HBV) infection is a major health problem and no cure exists. Importantly, hepatocyte intrusion by HBV particles results in a complex deregulation of both viral and host cellular genetic and epigenetic processes. Among the attempts to develop novel therapeutic approaches against HBV infection, several options targeting the epigenomic regulation of HBV replication are gaining attention. These include the experimental treatment with ‘epidrugs’. Moreover, as a targeted approach, the principle of ‘epigenetic editing’ recently is being exploited to control viral replication. Silencing of HBV by specific rewriting of epigenetic marks might diminish viral replication, viremia, and infectivity, eventually controlling the disease and its complications. Additionally, epigenetic editing can be used as an experimental tool to increase our limited understanding regarding the role of epigenetic modifications in viral infections. Aiming for permanent epigenetic reprogramming of the viral genome without unspecific side effects, this breakthrough may pave the roads for an ambitious technological pursuit: to start designing a curative approach utilizing manipulative molecular therapies for viral infections in vivo.
Conserved nucleolar stress at the onset of cell death
Authors: Golstein Pierre
Published: April 2017

Cell death pervasiveness among multicellular eukaryotes suggested that some core steps of cell death may be conserved. This could be addressed by comparing the course of cell death in organisms belonging to distinct eukaryotic kingdoms. A search for early cell death events in a protist revealed nucleolar disorganization similar to the nucleolar stress often reported in dying animal cells. This indicated a conserved role for the nucleolus at the onset of eukaryotic cell death and leads one to consider the course of cell death as a succession of unequally conserved modules.
Creep crack growth properties of P91 and P22 welded joints
Authors: Sedmak A. , Swei M. , Petrovski B.
Published: May 2017

The ferritic P22 and bainitic‐martenstic P91 steel welded joints operating at elevated temperatures are highly vulnerable to premature failure, because microstructure gradients can lead to cracking in the heat‐affected zone, commonly referred to as type IV cracking. Creep crack growth tests have been performed using compact tension specimens made of P91 and P22 weld joints at temperatures of 600 and 550 °C, respectively. The creep crack growth characterization through empirical equation of C* was the main fracture parameter for relating behaviour of component's regions. Results have shown that, for a specific value of C* parameter, the weld metal and heat‐affected zone had similar crack growth rates, which were about two times faster than base metal rates, because of lower creep strength that leads to a conclusion that the creep cracks will most likely initiate in the heat‐affected zone region.
Alternative biomass strategies for bioenergy: implications for bird communities across the southeastern United States
Authors: Gottlieb Isabel G. W. , Fletcher Robert J. , Nuñez‐Regueiro Mauricio M. , Ober Holly , Smith Lora , Brosi Berry J.
Published: April 2017

Concerns over energy demands and climate change have led the United States to set ambitious targets for bioenergy production in the coming decades. The southeastern United States has had a recent increase in biomass woody pellet production and is projected to produce a large portion of the nation's cellulosic biofuels. We conducted a large‐scale, systematic comparison of potential impacts of two types of bioenergy feedstocks – corn (Zea mays) and pine (Pinus spp.) – on bird communities across the southeastern United States. In addition, we evaluated three biomass alternatives for woody biomass from pine plantations: thinning, residue harvest, and short‐rotation energy plantations (SREPs). We conducted transect counts for birds in eight different land uses across the region (85 sites), including corn fields, reference forest, and plantation forests, 2013–2015. We then used hierarchical occupancy models to test the effect of these biomass alternatives on 31 species. Across all species, birds had lower rates of occupancy in corn fields compared to pine stands. Thinning had positive effects on the average occupancy across species, while residue harvest and the potential conversion of conventional plantations to SREPs had negative effects. Cavity nesters and species with bark‐gleaning foraging strategies tended to show the strongest responses. These results highlight the potential negative effects of corn as an energy crop relative to the use of pine biomass. In addition, harvesting biomass via thinning was a bird‐friendly harvest method in comparison with other alternatives. While SREPs may negatively impact some bird species, previously reported yields emphasize that they may provide an order of magnitude greater yield per unit area than other alternatives considered, such that this land‐use practice may be an important alternative to minimize the bioenergy impacts across the landscape.
The deterioration in physical function of hemodialysis patients
Authors: Sutcliffe Brianna K. , Bennett Paul N. , Fraser Steve F. , Mohebbi Mohammadreza
Published: May 2017

Introduction:Physical function in people on hemodialysis deteriorates significantly, however quantification of the rate of deterioration has not been well established. The aim of this study was to examine the rate of deterioration in objective physical function among end‐stage kidney disease patients receiving hemodialysis.

Methods:One hundred and ninety‐three participants (mean age 67.5 ±13.2 years, 60.6% males) receiving hemodialysis in Australia. Objective physical function was assessed via the 30‐second sit‐to‐stand and eight‐foot timed up‐and‐go at baseline, 12 and 24 weeks.

Findings:We found a decrease in the mean number 30‐second sit‐to‐stands performed from 10.0 (IQR, 4.0 to 13.0); 95% CI (8.0, 11.0) to 8.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 12 weeks to 7.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 24 weeks and a significant overall decreased rate (RR = 0.82; 95% CI, 0.80 to 0.85; P < 0.001). There was a decreased performance in the eight‐foot timed up‐and‐go time from 8.9 seconds (95% CI: 8.1 to 9.7) to 9.0 (95% CI: 8.1 to 9.7) after 12 weeks and further increasing to 9.7 (95% CI: 8.7 to 9.6) seconds after 24 weeks, and overall decreased rate (HR = 0.56; 95% CI, 0.39 to 0.80; P = 0.001) between baseline and week 24.

Discussion:Physical function significantly decreases on hemodialysis. Exercise programs to address this physical function decline should be included in hemodialysis treatment regimens.
Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C
Authors: Atsukawa Masanori , Tsubota Akihito , Koushima Yohei , Ikegami Tadashi , Watanabe Kouji , Shimada Noritomo , Sato Shinichi , Kato Keizo , Abe Hiroshi , Okubo Tomomi , Arai Taeang , Itokawa Norio , Kondo Chisa , Mikami Shigeru , Asano Toru , Chuganji Yoshimichi , Matsuzaki Yasushi , Iwakiri Katsuhiko
Published: April 2017

Aim

From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis.

Methods

A retrospective, multicenter study evaluated the outcome of 12‐week ombitasvir (non‐structural protein [NS]5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir combination therapy for dialysis patients. The primary end‐point was sustained virologic response 12 weeks after therapy (SVR12).

Results

The subjects were 31 patients with a median age of 64 years (range, 49–85 years), including 10 cirrhotic patients. All of the 31 patients had an estimated glomerular filtration rate level <15 mL/min/1.73 m2, defined as end‐stage renal disease (ESRD). Pre‐existing resistance‐associated substitutions at position L31 and Y93 of the NS5A region were detected in 0% and 3.6% (1/28), respectively. The rates of rapid virologic response, end‐of‐treatment response, and SVR12 were 93.5% (29/31), 100% (31/31), and 96.8% (30/31), respectively. The incidence of adverse events was 35.5% (11/31). Of the 11 patients, one discontinued the treatment due to erythema multiforme and thereafter relapsed. The most frequent adverse event was pruritus (6.5%; 2/31).

Conclusions

The present study suggests that ombitasvir/paritaprevir/ritonavir combination therapy is effective and safe for genotype 1b chronic hepatitis C patients undergoing dialysis due to ESRD.
Frequency mixing application based on BaTiO3 ceramic: Design and functional characterization
Authors: Pop Mihai V. , Horchidan Nadejda , Ianculescu Adelina C. , Mitoseriu Liliana
Published: April 2017

In the present article, we propose a ferroelectric‐based frequency mixer capable of reconfigurable functioning, a key trait in multi frequency band coverage, based on the nonlinear dielectric properties of BaSnxTi1−xO3 ceramics. According to the properties of BaSnxTi1−xO3 solid solutions, an optimum composition was selected to demonstrate the applicability as a discrete passive mixer with a simple coplanar geometry. A prototype device, with four coplanar capacitors, connected in a circular electric circuit was built on the surface of the selected ceramic. In this configuration, mixing products of the pumping and working signals were obtained and characterized.
Low‐temperature sintering and electrical properties of Sr2Nb2O7 piezoceramics by CuO addition
Authors: Chen Tao , Liang Ruihong , Jiang Kai , Hu Zhigao , Zhou Zhiyong , Dong Xianlin
Published: May 2017

Effects of 0.5 wt% CuO addition on the sintering, structural and electrical properties of perovskite layer structured (PLS) Sr2Nb2O7 ceramics prepared by solid‐state reaction method are investigated. The addition of CuO is beneficial to the liquid phase bridge formation at sintering process, leading to lower sintering temperature of 1180°C and larger bulk density up to 98%. Meanwhile, CuO modified Sr2Nb2O7 ceramics show a remarkable d33 of (1.1 ± 0.1) pC/N while still with a very high Tc of (1340 ± 2)°C. Raman spectra indicate that the improvement of piezoelectricity could be attributed to the rotation and/or distortion of oxygen octahedron caused by possible Cu2+ substitution at the A‐sites of Sr2Nb2O7.
Identification of residual stress layers at glass surfaces via crack terminating angles
Authors: Schell Karl G. , Wagner Susanne , Hettich Pascal , Fett Theo , Rizzi Gabriele , Hoffmann Michael J.
Published: May 2017

Cracks terminating at free surfaces are affected by local stresses in the surface region. Under residual compression the crack front must retard compared with the crack contour in the absence of stresses. This effect can be used for an identification of residual stresses at glass surfaces. For an illustration of the procedure, Vickers indentation tests in soda‐lime glass are considered. Specimens treated by ion exchange and chemically toughening showed reduced terminating angles compared with untreated glass.
The experience of adolescent motherhood: An exploratory mixed methods study
Authors: Kagawa Rose M. C. , Deardorff Julianna , Domínguez Esponda Rosalinda , Craig Darcy , Fernald Lia C. H.
Published: May 2017

Aim

To identify and better understand opportunities for and challenges in attaining the maternal role among women who began childbearing in adolescence in rural Mexico.

Background

Adolescent mothers often face challenges rising from their socioeconomic status and developmental stage that can strain the process of developing confidence and competence in the maternal role. In Mexico, 19% of births are to women under age 20. Little is known about these mothers’ experiences with parenting.

Design

Mixed methods.

Methods

Quantitative data collected in 2008 from a cluster‐random sample of mothers (n = 1,381) in rural, impoverished areas of three southern states provided objective measures of mothers’ socioeconomic position, well‐being, and parenting practices. Semi‐structured interviews conducted in 2013 with mothers (n = 30) provided insight into perceptions of motherhood and opportunities for and challenges in attaining the maternal role.

Findings

Ever‐adolescent mothers scored lower than never‐adolescent mothers on the total HOME and the parental responsivity and learning materials subscales. They also occupied the most economically disadvantaged positions, showing the lowest levels of education and wealth and the most depressive symptoms compared with never‐adolescent mothers. The qualitative analysis supported these challenges and highlighted areas of opportunity: (1) early‐adolescent parents faced economic challenges; (2) adolescent childbearing was normative with some exceptions; (3) participants’ mothers and mothers‐in‐law provided social support; and (4) mothers focused on learning to parent and helping their children “get ahead” in life.

Conclusion

Findings have important implications for identifying how to support young women as they become mothers and continue in this role.
Three‐dimensional microstructure characterisation of thermoplastic polyolefin blends
Authors: LIN J.‐C. , HUANG Y. , HARRIS J. , WEINLANDER B. , JONES M.A.
Published: May 2017

The size, shape and distribution of different phases in thermoplastic polyolefin (TPO) blends and composites are critical to the properties of the materials, but can be difficult to characterise. Here we report the combination of heavy metal staining and focused ion beam – scanning electron microscopy (FIB‐SEM) to reveal the three‐dimensional (3D) structure of an elastomer‐modified poly(propylene) and a talc filled elastomer‐modified poly(propylene). High‐quality, high‐resolution serial images were collected and the 3D structures were characterised quantitatively.
Assessment of statistical agreement of three techniques for the study of cut marks: 3D digital microscope, laser scanning confocal microscopy and micro‐photogrammetry
Authors: MATÉ‐GONZÁLEZ MIGUEL ÁNGEL , ARAMENDI JULIA , YRAVEDRA JOSÉ , BLASCO RUTH , ROSELL JORDI , GONZÁLEZ‐AGUILERA DIEGO , DOMÍNGUEZ‐RODRIGO MANUEL
Published: May 2017

In the last few years, the study of cut marks on bone surfaces has become fundamental for the interpretation of prehistoric butchery practices. Due to the difficulties in the correct identification of cut marks, many criteria for their description and classification have been suggested. Different techniques, such as three‐dimensional digital microscope (3D DM), laser scanning confocal microscopy (LSCM) and micro‐photogrammetry (M‐PG) have been recently applied to the study of cut marks. Although the 3D DM and LSCM microscopic techniques are the most commonly used for the 3D identification of cut marks, M‐PG has also proved to be very efficient and a low‐cost method. M‐PG is a noninvasive technique that allows the study of the cortical surface without any previous preparation of the samples, and that generates high‐resolution models. Despite the current application of microscopic and micro‐photogrammetric techniques to taphonomy, their reliability has never been tested. In this paper, we compare 3D DM, LSCM and M‐PG in order to assess their resolution and results. In this study, we analyse 26 experimental cut marks generated with a metal knife. The quantitative and qualitative information registered is analysed by means of standard multivariate statistics and geometric morphometrics to assess the similarities and differences obtained with the different methodologies.
Patterns and regulation of silicon accumulation in Synechococcus spp.
Authors: Brzezinski Mark A. , Krause Jeffrey W. , Baines Stephen B. , Collier Jackie L. , Ohnemus Daniel C. , Twining Benjamin S.
Published: April 2017

Six clones of the marine cyanobacterium Synechococcus, representing four major clades, were all found to contain significant amounts of silicon in culture. Growth rate was unaffected by silicic acid, Si(OH)4, concentration between 1 and 120 μM suggesting that Synechococcus lacks an obligate need for silicon (Si). Strains contained two major pools of Si: an aqueous soluble and an aqueous insoluble pool. Soluble pool sizes correspond to estimated intracellular dissolved Si concentrations of 2–24 mM, which would be thermodynamically unstable implying the binding of intracellular soluble Si to organic ligands. The Si content of all clones was inversely related to growth rate and increased with higher [Si(OH)4] in the growth medium. Accumulation rates showed a unique bilinear response to increasing [Si(OH)4] from 1 to 500 μM with the rate of Si acquisition increasing abruptly between 80 and 100 μM Si(OH)4. Although these linear responses imply some form of diffusion‐mediated transport, Si uptake rates at low Si (~1 μM Si) were inhibited by orthophosphate, suggesting a role of phosphate transporters in Si acquisition. Theoretical calculations imply that observed Si acquisition rates are too rapid to be supported by lipid‐solubility diffusion of Si through the plasmalemma; however, facilitated diffusion involving membrane protein channels may suffice. The data are used to construct a working model of the mechanisms governing the Si content and rate of Si acquisition in Synechococcus.
Evaluation of cardiovascular effects of intravenous robenacoxib in dogs
Authors: Desevaux C. , Marotte‐Weyn A‐A. , Champeroux P. , King J. N.
Published: April 2017

The objective of the study was to assess the cardiovascular effects of intravenous (IV) dosing with robenacoxib (Onsior®) in conscious adult healthy beagle dogs. The study employed a randomized, open, placebo‐controlled, four‐phase Latin square design. A total of eight dogs received a single dose of 2 mg/kg and 4 mg/kg IV robenacoxib (test groups), 2 mg/kg subcutaneous (SC) robenacoxib (reference dose and route), and IV isotonic saline (control). There were no significant differences between groups for clinical observations, buccal mucosal bleeding time or blood hematology, coagulation, and clinical chemistry variables in all eight dogs. In a subset of four dogs, no significant differences between groups were detected using telemetric assessment for arterial blood pressure, heart rate, electrocardiogram, or body temperature over 8 hr postdose. In conclusion, no significant cardiovascular effects were detected after a single IV dose of 2 or 4 mg/kg robenacoxib in conscious healthy dogs.
Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin
Authors: Foster D. M. , Sylvester H. J. , Papich M. G.
Published: April 2017

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril®100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil®300) was administered at a dose of 20 mg/kgSC.PELF, sampled by two different methods—bronchoalveolar lavage (BAL) and direct sampling (DS)—plasma, andISFwere collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin byHPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured byAUCinDSsamples was 137 ± 72% higher than in plasma, but inBALsamples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin inDSandBALsamples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected byDSwere significantly different than those collected byBAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded theMICvalues for bovine respiratory disease pathogens but tilmicosin did not reachMIClevels for these pathogens in any fluids.
Pharmacokinetics of grapiprant, a selective EP4 prostaglandin PGE2 receptor antagonist, after 2 mg/kg oral and i.v. administrations in cats
Authors: Lebkowska‐Wieruszewska B. , De Vito V. , Owen H. , Poapholatep A. , Giorgi M.
Published: April 2017

Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method.

After both administrations, grapiprant concentrations were detectable in plasma for up to 24 hr in five of six animals. The critical parameters including clearance (173.2 ml hr−1 kg−1, range 120–326 ml hr−1 kg−1) and volume of distribution (918 ml/kg, range 611–1608 ml/kg) were calculated from the i.v. group. The mean oral F% was low (39.6% range 31.5%–45.2%).

If the assumption that the minimal effective concentration in dogs (164 ng/ml) applies in cats too, grapiprant orally administered at 2 mg/kg might be effective for 10 hr. Further studies are necessary to establish the minimal effective concentration in this animal species.
VII. REPLICATION, RESEARCH ACCUMULATION, AND META‐ANALYSIS IN DEVELOPMENTAL SCIENCE
Authors: Card Noel A.
Published: May 2017

The progression of scientific knowledge requires replication of research results and an orderly accumulation of research knowledge. However, developmental science, like many other sciences, has too often prioritized individual studies at the expense of replication and synthesis efforts. In this chapter, I describe the concepts of replication and research accumulation and consider both their barriers and potentials for developmental science. I emphasize the importance of considering effect sizes rather than statistical significance, and I describe meta‐analysis as a powerful tool in facilitating research accumulation and in guiding replication efforts. By considering advancement in terms of research accumulation rather than single studies, developmental science can achieve greater efficiency and precision to guide both future research and applied efforts.
Orthodoxy, Orthopraxis, and Orthopathy: Evaluating the Feminist Kenosis Debate
Authors: Selak Annie
Published: May 2017

This study examines the feminist kenosis debate, tracing its development through Daphne Hampson, Sarah Coakley, Aristotle Papanikolaou, Carolyn Chau, Jennifer Newsome Martin and Anna Mercedes. Given the diversity of theologies put forth in this debate, it is necessary to have a method of evaluation. In order to do this, I will introduce the theology of Jon Sobrino to the feminist kenosis conversation. Sobrino's notions of orthodoxy, orthopraxis, and orthopathy are essential tools for assessing different interpretations of kenosis and advancing an adequate theology of “self‐emptying.” This analysis leads to a proposal for a comprehensive feminist theological view of kenosis.
Modulation of the N400 component in relation to hypomanic personality traits in a word meaning ambiguity resolution task
Authors: Raucher‐Chéné Delphine , Terrien Sarah , Gobin Pamela , Gierski Fabien , Kaladjian Arthur , Besche‐Richard Chrystel
Published: April 2017

Aim

High levels of hypomanic personality traits have been associated with an increased risk of developing bipolar disorder (BD). Changes in semantic content, impaired verbal associations, abnormal prosody, and abnormal speed of language are core features of BD, and are thought to be related to semantic processing abnormalities. In the present study, we used event‐related potentials to investigate the relation between semantic processing (N400 component) and hypomanic personality traits.

Methods

We assessed 65 healthy young adults on the Hypomanic Personality Scale (HPS). Event‐related potentials were recorded during a semantic ambiguity resolution task exploring semantic ambiguity (polysemous word ending a sentence) and congruency (target word semantically related to the sentence).

Results

As expected, semantic ambiguity and congruency both elicited an N400 effect across our sample. Correlation analyses showed a significant positive relationship between the Social Vitality subscore of the HPS and N400 modulation in the frontal region of interest in the incongruent unambiguous condition, and in the frontocentral region of interest in the incongruent ambiguous condition.

Conclusion

We found differences in semantic processing (i.e., detection of incongruence and semantic inhibition) in individuals with higher Social Vitality subscores. In the light of the literature, we discuss the notion that a semantic processing impairment could be a potential marker of vulnerability to BD, and one that needs to be explored further in this clinical population.