bluuebunny/crossref_metadata_2025 huggingface dataset:
Mangrove‐forest evolution in a sediment‐rich estuarine system: opportunists or agents of geomorphic change?
Authors: Swales Andrew , Bentley Samuel J. , Lovelock Catherine E.
Published: May 2015

The majority of the world's mangrove forests occur on mostly mineral sediments of fluvial origin. Two perspectives exist on the biogeomorphic development of these forests, i.e. that mangroves are opportunistic, with forest development primarily driven by physical processes, or alternatively that biophysical feedbacks strongly influence sedimentation and resulting geomorphology. On the Firth of Thames coast, New Zealand, we evaluate these two possible scenarios for sediment accumulation and forest development using high‐resolution sedimentary records and a detailed chronology of mangrove‐forest (Avicennia marina) development since the 1950s. Cores were collected along a shore‐normal transect of known elevation relative to mean sea level (MSL). Activities for lead‐210 (210Pb), caesium‐137 (137Cs) and beryllium‐7 (7Be), and sediment properties were analysed, with 210Pb sediment accumulation rates (SARs), compensated for deep subsidence (~8 mm yr−1) used as a proxy for elevation gain. At least four phases of forest development since the 1950s are recognized. An old‐growth forest developed by the late‐1970s with more recent seaward forest expansion thereafter. Excess 210Pb profiles from the old‐growth forest exhibit relatively low SARs near the top (7–12 mm yr−1) and bottom (10–22 mm yr−1) of cores, separated by an interval of higher SARs (33–100 mm yr−1). A general trend of increasing SAR over time characterizes the recent forest. Biogeomorphic evolution of the system is more complex than simple mudflat accretion/progradation and mangrove‐forest expansion. Surface‐elevation gain in the old‐growth forest displays an asymptotic trajectory, with a secondary depocentre developing on the seaward mudflat from the mid‐1970s. Two‐ to ten‐fold increases in 210Pb SARs are unambiguously large and occurred years to decades before seedling recruitment, demonstrating that mangroves do not measurably enhance sedimentation over annual to decadal timescales. This suggests that mangrove‐forest development is largely dependent on physical processes, with forests occupying mudflats once they reach a suitable elevation in the intertidal. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis of Novel Substituted Indazoles via Nucleophilic Substitution of Hydrogen (SNH)
Authors: Kouakou Assoman , Abbassi Najat , Chicha Hakima , Ammari Lahcen El , Saadi Mohamed , Rakib El Mostapha
Published: May 2015

New four‐substituted indazoles 4a–e were synthesized by regioselective nucleophilic substitution of hydrogen of N‐alkyl‐7‐nitroindazoles 2a,b with arylacetonitriles 3a–c. Compounds 4a–e were reacted with arylsulfonyl chloride in pyridine to give some new indazole linked sulfonamides with good yields. The SNH at position C‐4 of 7‐nitroindazole with arylacetonitrile is confirmed by X‐ray diffraction analysis of compounds 4e and 6a.
A systematic study on dysregulated microRNAs in cervical cancer development
Authors: He Yuqing , Lin Juanjuan , Ding Yuanlin , Liu Guodong , Luo Yanhong , Huang Mingyuan , Xu Chengkai , Kim Taek‐Kyun , Etheridge Alton , Lin Mi , Kong Danli , Wang Kai
Published: May 2015

MicroRNAs (miRNAs) are short regulatory RNAs that modulate the transcriptome and proteome at the post‐transcriptional level. To obtain a better understanding on the role of miRNAs in the progression of cervical cancer, meta‐analysis and gene set enrichment analysis were used to analyze published cervical cancer miRNA studies. From 85 published reports, which include 3,922 cases and 2,099 noncancerous control tissue samples, 63 differentially expressed miRNAs (DEmiRNAs) were identified in different stages of cervical cancer development (CIN 1‐3 and CC). It was found that some of the dysregulated miRNAs were associated with specific stages of cervical cancer development. To illustrate the impact of miRNAs on the pathogenesis of cervical cancer, a miRNA‐mRNA interaction network on selected pathways was built by integrating viral oncoproteins, dysregulated miRNAs and their predicted/validated targets. The results indicated that the deregulated miRNAs at the different stages of cervical cancer were functionally involved in several key cancer related pathways, such as cell cycle, p53 and Wnt signaling pathways. These dysregulated miRNAs could play an important role in cervical cancer development. Some of the stage‐specific miRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cancer development.
Methyl and Dimethyl o‐Xylenyl‐Substituted Fullerene Acceptors for Polymer Solar Cells
Authors: Kim Hee Un , Park Jong Baek , Grimsdale Andrew C. , Hwang Do‐Hoon
Published: May 2015

A series of fullerene derivatives based on methyl‐ and dimethyl‐substituted o‐xylenyl groups were synthesized via DielsAlder reaction from fullerene (C60) and dienes derived from α,α′‐dibromo‐o‐xylene derivatives. The synthesized 1‐methyl‐4,5‐xylenyl‐ and 1,2‐dimethyl‐4,5‐xylenyl‐substituted fullerene mono‐, bis‐, and trisadducts, i.e., M_OXCMA, M_OXCBA, M_OXCTA, DM_OXCMA, DM_OXCBA, and DM_OXCTA, were used as electron‐acceptor materials for polymer solar cells and have good solubility in common organic solvents. The SternVolmer quenching constants for poly(3‐hexylthiophene) (P3HT) as a fluorophore with M_OXCMA, M_OXCBA, M_OXCTA, DM_OXCMA, DM_OXCBA, and DM_OXCTA as quenchers were 1.35×104, 7.67×103, 3.72×103, 1.38×104, 7.95×103, and 4.10×103 M−1, respectively. These values correlate with the binding affinities of the fluorophore and quencher. The lowest unoccupied molecular orbital energy levels increased with increasing number of adducts on the fullerene because of their decreasing number of sp2‐hybridized carbons. Photovoltaic devices were fabricated using P3HT and the mono‐, bis‐, and trisadducts as electron donors and acceptors, respectively. Among these, the cells with an ITO/PEDOT : PSS/P3HT : DM_OXCBA/LiF/Al structure had the highest power conversion efficiency of 4.77 % with an open‐circuit voltage of 0.88 V, a short‐circuit current density of 10.52 mA cm−2, and a fill factor of 0.51 under AM 1.5G (100 mW cm−2) illumination.
Trends in Media Reports, Oral Bisphosphonate Prescriptions, and Hip Fractures 1996–2012: An Ecological Analysis
Authors: Jha Smita , Wang Zhong , Laucis Nicholas , Bhattacharyya Timothy
Published: May 2015

Bisphosphonates are effective for the treatment of osteoporosis despite recent reports of safety concerns such as atypical femur fracture. We conducted an ecological analysis of relevant media reports, oral bisphosphonate use, and fracture outcomes in the United States. Trends in media reports and public interest of bisphosphonates were quantified using data from Google Trends. Data from the Medical Expenditure Panel Survey (MEPS) and the National Inpatient Sample (NIS) were used to estimate the trends in oral bisphosphonate use among patients aged 55 years and older and hospitalizations for intertrochanteric and subtrochanteric fractures, respectively. These trends in the prevalence of oral bisphosphonate use and the age-adjusted incidence rate of intertrochanteric and subtrochanteric fractures were examined from 1996 to 2012. A series of spikes in Internet search activity for alendronate (Fosamax) occurred between 2006 and 2010 immediately following media reports of safety concerns. Oral bisphosphonate use declined by greater than 50% between 2008 and 2012 (p < 0.001) after increasing use for more than a decade. The decline was more common in patients with lower education levels. Intertrochanteric hip fractures declined from 1996 through 2006 (p < 0.001) and continued to decline from 2008 to 2012 (p < 0.05). Subtrochanteric and diaphyseal fractures showed a steady and significant increase from 2002 to 2011 (p < 0.05). However, the incidence decreased from a peak of 30.5 per 100,000 in 2011 to 26.7 per 100,000 in 2012. The plateauing and subsequent decline in oral bisphosphonate use since 2006 coincided with reports of safety concerns of bisphosphonates, despite the fact that U.S. Food and Drug Administration (FDA) and American Society of Bone and Mineral Research (ASBMR) reports did not recommend any safety restrictions on their use. This decline in oral bisphosphonate use was followed by the decline in the incidence of subtrochanteric and diaphyseal fractures. © 2015 American Society for Bone and Mineral Research.
The amount effect and marginal value
Authors: Rachlin Howard , Arfer Kodi B. , Safin Vasiliy , Yen Ming
Published: May 2015

The amount effect of delay discounting (by which the value of larger reward amounts is discounted by delay at a lower rate than that of smaller amounts) strictly implies that value functions (value as a function of amount) are steeper at greater delays than they are at lesser delays. That is, the amount effect and the difference in value functions at different delays are actually a single empirical finding. Amount effects of delay discounting are typically found with choice experiments. Value functions for immediate rewards have been empirically obtained by direct judgment. (Value functions for delayed rewards have not been previously obtained.) The present experiment obtained value functions for both immediate and delayed rewards by direct judgment and found them to be steeper when the rewards were delayed—hence, finding an amount effect with delay discounting.
Novel π2s+π2a Electrocyclization of Triethylenic‐Malonic Acids Exemplified for a One‐Pot Synthesis of New γ‐Dilactones cis‐Fused with a Cyclopentene
Authors: Dillenschneider Jean‐Marc , Dufossé Laurent , Fouillaud Mireille , Sutthiwong Nuthathai , Labia Roger , Valla Alain
Published: May 2015

A new, easy and rapid synthesis of γ‐dilactones is cis‐fused with a cyclopentenic ring via cyclization of 7‐chlorotriethylenic‐malonic acids. The key step implicates an intramolecular cyclization to a cyclopentenyl cation, according to an electrocyclic π2s + π2a conrotatory process. This cyclopentenyl cation led to unstable γ‐lactones intermediates that are rearrange to more stable isomers. δ‐lactones (6Z and 6E‐(3‐chlorobut‐2‐en‐2‐yl)‐5‐methyl‐3,6‐dihydro‐2H‐pyran‐2‐one) were obtained as secondary products. Mechanistic pathways were considered. The structures of the newly synthesized compounds were established by elemental and spectral data.
Quinoline Synthesis by the Reaction of Anilines with 1,2‐diols Catalyzed by Iron Compounds
Authors: Khusnutdinov Ravil , Bayguzina Alfiya , Aminov Rishat , Dzhemilev Usein
Published: May 2015

The synthesis of quinoline derivatives by cyclocondensation of anilines with 1,2‐ethanediol, 1,2‐propanediol, and 1,2‐butanediol in the presence of iron‐containing catalysts was performed for the first time.
Regioselectively Synthesis of Thiazolo[4,5‐a]acridines and Oxazolo[5,4‐a]thiazolo[5,4‐j]acridines via Multicomponent Domino Reactions
Authors: Xie Xin , Zhang Fan , Geng De‐Min , Wang Li‐Li , Hao Wen‐Juan , Jiang Bo , Tu Shu‐Jiang
Published: May 2015

A regioselective three‐component reaction of aromatic aldehydes, 2‐hydroxy‐1,4‐naphthoquinone and benzo[d]thiazol‐5‐amine in HOAc under microwave irradiation has been developed. A series of new thiazolo‐fused benzo[h]acridines were synthesized with high chemical yields in this one‐pot reaction. The resulting thiazolo‐fused acridines were employed to further react with aldehydes and ammonium acetate to give polycyclic‐fused oxazolo[5,4‐a]thiazolo[5,4‐j]acridines. The present synthesis shows several advantages, such as operational simplicity, fast reaction rates, which makes it a useful and attractive process of library generation for drug discovery.
Improving patient satisfaction through physician education, feedback, and incentives
Authors: Banka Gaurav , Edgington Sarah , Kyulo Namgyal , Padilla Tony , Mosley Virgie , Afsarmanesh Nasim , Fonarow Gregg C. , Ong Michael K.
Published: May 2015

BACKGROUND

Patient satisfaction has been associated with improved outcomes and become a focus of reimbursement.

OBJECTIVE

Evaluate an intervention to improve patient satisfaction.

DESIGN

Nonrandomized, pre‐post study that took place from 2011 to 2012.

SETTING

Large tertiary academic medical center.

PARTICIPANTS

Internal medicine (IM) resident physicians, non‐IM resident physicians, and adult patients of the resident physicians.

INTERVENTION

IM resident physicians were provided with patient satisfaction education through a conference, real‐time individualized patient satisfaction score feedback, monthly recognition, and incentives for high patient‐satisfaction scores.

MAIN MEASURES

Patient satisfaction on physician‐related and overall satisfaction questions on the HCAHPS survey. We conducted a difference‐in‐differences regression analysis comparing IM and non‐IM patient responses, adjusting for differences in patient characteristics.

KEY RESULTS

In our regression analysis, the percentage of patients who responded positively to all 3 physician‐related Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) questions increased by 8.1% in the IM and 1.5% in the control cohorts (absolute difference 6.6%,P = 0.04). The percentage of patients who would definitely recommend this hospital to friends and family increased by 7.1% in the IM and 1.5% in the control cohorts (absolute difference 5.6%,P = 0.02). The national average for the HCAHPS outcomes studied improved by no more than 3.1%.

LIMITATIONS

This study was nonrandomized and was conducted at a single site.

CONCLUSION

To our knowledge, this is the first intervention associated with a significant improvement in HCAHPS scores. This may serve as a model to increase patient satisfaction, hospital revenue, and train resident physicians.Journal of Hospital Medicine2015;10:497–502. © 2015 Society of Hospital Medicine
Corticosteroids and low bone mineral density affect hip cartilage in systemic lupus erythematosus patients: Quantitative T2 mapping
Authors: Hagiwara Shigeo , Nakamura Junichi , Watanabe Atsuya , Kishida Shunji , Ohtori Seiji , Omae Takanori , Miyamoto Shuichi , Orita Sumihisa , Takahashi Kazuhisa
Published: May 2015

Background

The purpose of this diagnostic study was to quantify the effect of high‐dose corticosteroid treatment on hip joint cartilage degeneration in patients with systemic lupus erythematosus (SLE), with and without osteonecrosis, using magnetic resonance imaging (MRI).

Methods

T2 mapping, with a 3.0 Tesla Discovery MR750 (GE Healthcare) MRI scanner, was performed in 12 volunteers without hip pathology (control group, 12 hips), in 11 patients with SLE without osteonecrosis, who were receiving corticosteroid therapy (corticosteroid‐ON group, 17 hips), and in 15 patients with SLE receiving corticosteroids, who had noncollapsed and asymptomatic osteonecrosis (corticosteroid+ON group, 26 hips). The distribution of T2 values in the femoral head and acetabular cartilage were compared among the three groups. Step‐wise multiple regression analysis was performed to determine the prognostic factors for T2 values indicative of femoral head cartilage degeneration.

Results

Mean T2 values of femoral head cartilage were significantly higher in the corticosteroid‐ON (40.3 ms) and corticosteroid+ON (35.2 ms) groups than in the control group (30.1 ms, P = 0.001). T2 values of acetabular cartilage were significantly higher in the corticosteroid‐ON group (41.8 ms) versus the control (33.4 ms) and the corticosteroid+ON groups (37.0 ms; P = 0.001). Low bone mineral density was a significant prognostic factor for high T2 values of cartilage at the femoral head in patients treated with corticosteroids, regardless of whether they had osteonecrosis.

Conclusion

T2 mapping suggests that corticosteroid therapy and osteoporosis are independent risk factors for cartilage degeneration at the femoral head in patients with SLE. J. MAGN. RESON. IMAGING 2015;42:1524–1531.
Cartilage repair by human umbilical cord blood‐derived mesenchymal stem cells with different hydrogels in a rat model
Authors: Park Yong‐Beom , Song Minjung , Lee Choong‐Hee , Kim Jin‐A , Ha Chul‐Won
Published: May 2015

This study was carried out to assess the feasibility of human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB‐MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB‐MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB‐MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB‐MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydorgel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB‐MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1580–1586, 2015.
Impact of laryngologist and speech pathologist coassessment on outcomes and billing revenue
Authors: Litts Juliana K. , Gartner‐Schmidt Jackie L. , Clary Matthew S. , Gillespie Amanda I.
Published: May 2015

Objectives/Hypothesis

This study investigated financial and treatment implications of a speech‐language pathologist (SLP) performing a voice evaluation at the initial laryngologic visit.

Study Design

Retrospective chart review.

Methods

Medical records from 75 consecutive adult voice therapy patients during a 3‐month period were categorized into two groups: group 1 (n = 37) represented patients who underwent a medical speech evaluation (MSE) at the initial voice assessment with the laryngologist (+SLP), and group 2 (n = 38) represented patients who did not receive an MSE (−SLP). Data collected included age, gender, voice diagnosis, number of therapy sessions attended and cancelled, reason for discharge, and pre– and post–voice therapy Voice Handicap Index‐10 (VHI‐10) scores.

Results

Patients in the +SLP group had fewer cancellations (P = 0.001), greater change in VHI‐10 from pre‐ to post‐therapy (P = .001), and were more likely to be discharged from therapy having met therapeutic goals (P = .007) than patients in the −SLP group. In addition, lost revenue over 3 months due to cancellations/no‐shows was $2,260 in the +SLP group compared to $7,030 in the −SLP group (P < .001).

Conclusions

Concurrent voice evaluation by an SLP and laryngologist at initial diagnostic visit affects therapy attendance, voice therapy outcomes, and ultimately SLP and departmental billing revenue. Results may be due to more appropriate therapy referrals from SLP assessment of patients in conjunction with a laryngologist.

Level of Evidence

4 Laryngoscope, 125:2139–2142, 2015
Temporoparietal fascia flap “sandwich” technique for repair of near‐total traumatic auricle avulsion
Authors: Kong Derek Kai , Schutt Christopher A. , Mehra Saral
Published: May 2015

NA Laryngoscope, 126:826–828, 2016
Phytoprostanes
Authors: Collado‐González Jacinta , Durand Thierry , Ferreres Federico , Medina Sonia , Torrecillas Arturo , Gil‐Izquierdo Ángel
Published: May 2015

Phytoprostanes are non‐enzymatic lipid peroxidation products derived from α‐linolenic acid. Phytoprostanes are not essential for the metabolic activity of living cells but they are considered components of oxidative injury‐sensing systems and act as excellent biomarkers of oxidative degradation in plant‐derived foodstuffs. They can be quickly and accurately quantified by UHPLC/MS‐MS. Specific agronomic and industrial practices can enhance the phytoprostanes content of fruits and seeds and derived vegetable oils. In vitro studies have shown positive biological activities of these compounds and according to existing reports they are orally bioavailable. Further studies are required to comprehensively study the bioavailability and physiological effects of the phytoprostanes.
ω3‐polyunsaturated fatty acids suppress lipoprotein‐associated phospholipase A2 expression in macrophages and animal models
Authors: Li Zhuang , Ren Wenzhi , Han Xiaolei , Liu Xingxing , Wang Gangqi , Zhang Mingjun , Pang Daxin , Ouyang Hongsheng , Tang Xiaochun
Published: May 2015

Scope

ω3‐polyunsaturated fatty acids (ω3‐PUFAs) have beneficial effects on cardiovascular function, and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is associated with the risk of cardiovascular disease. Here, we investigated the effects of ω3‐PUFAs on Lp‐PLA2 expression in vitro and in vivo and explored the mechanisms involved.

Methods and results

Human monocyticcells (THP‐1) were induced into macrophages in an in vitro model. ω3‐PUFAs suppressed Lp‐PLA2 expression; the suppression induced by docosahexaenoic acid (DHA) was related to reduced inflammation. Tumor necrosis factor‐α (TNF‐α) was employed to stimulate the phosphorylation of p38 mitogen‐activated protein kinase (MAPK), nuclear factor‐κB (NF‐κB) p65 and Lp‐PLA2 expression in macrophages. The stimulation was inhibited by DHA and the anti‐inflammatory drug sodium salicylate. Moreover, the stimulation of Lp‐PLA2 expression by TNF‐α could be suppressed by NF‐κB and MAPK pathway inhibitors. Then, chronic inflammation was induced in an in vivo mouse model, resulting in an increase in Lp‐PLA2 expression in peripheral blood mononuclear cells (PBMCs) and arteries. This increase was suppressed by ω3‐PUFAs. Inhibition of Lp‐PLA2 transcription in PBMCs was also observed in ω3‐PUFA‐enriched swine.

Conclusion

Our results demonstrate that the protective effects of ω3‐PUFAs against cardiovascular events may be related to the suppression of Lp‐PLA2 levels.
Egg ovotransferrin‐derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats
Authors: Majumder Kaustav , Liang Guanxiang , Chen Yanhong , Guan LeLuo , Davidge Sandra T. , Wu Jianping
Published: May 2015

Scope

Egg ovotransferrin‐derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide‐mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique.

Methods and results

Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW‐treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW‐treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE‐2, ABCB‐1, IRF‐8, and CDH‐1 while significantly decreased the expression ICAM‐1 and VCAM‐1 in mesenteric arteries.

Conclusion

Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression.
Lutein suppresses inflammatory responses through Nrf2 activation and NF‐κB inactivation in lipopolysaccharide‐stimulated BV‐2 microglia
Authors: Wu Wanqiang , Li Yuelian , Wu Yue , Zhang Yawen , Wang Zhen , Liu Xuebo
Published: May 2015

Scope

In this study, the effects of lutein on neuroinflammation in lipopolysaccharide (LPS)‐activated BV‐2 microglia were investigated.

Methods and results

The production of proinflammatory cytokines tumor necrosis factor‐α, interleukin‐1β, and nitric oxide was measured in culture medium using enzyme immunoassay and Griess reagent, respectively. The expression of proteins was determined using Western blot. Pretreatment with lutein (50 μM) prior to LPS (1 μg/mL, 12 h) stimulation resulted in a significant inhibition of inducible nitric oxide synthase and cyclooxygenase‐2 expression, as well as tumor necrosis factor‐α, interleukin‐1β, and nitric oxide production (p < 0.05). Further experiments demonstrated that lutein suppressed LPS‐induced NF‐κB activation by inhibiting the phosphorylation of p38 kinase, c‐Jun N‐terminal kinase (JNK), and Akt kinase (p < 0.05). Moreover, lutein markedly quenched reactive oxygen species and promoted antioxidant protein expression including heme oxygenase‐1 and NAD(P)H:quinone oxidoreductase by enhancing the phosphorylation of extracellular signal‐regulated kinase 1/2 (ERK1/2) mediated NF‐E2‐related factor 2 (Nrf2) activation (p < 0.05).

Conclusion

These results suggest that lutein attenuates neuroinflammation in LPS‐activated BV‐2 microglia partly through inhibiting p38‐, JNK‐, and Akt‐stimulated NF‐κB activation and promoting ERK‐induced Nrf2 activation, suggesting that lutein has great potential as a nutritional preventive strategy in inflammation‐related neurodegenerative disorders.
Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1‐13c]pyruvate
Authors: Laustsen Christoffer , Hansen Esben Søvsø Szocska , Kjærgaard Uffe , Bertelsen Lotte Bonde , Ringgaard Steffen , Stødkilde‐Jørgensen Hans
Published: May 2015

Purpose

Our aim was to determine the quantitative reproducibility of metabolic breakdown products in the kidney following intravenous injection of hyperpolarized [1‐13C]pyruvate and secondly to investigate the metabolic effect on the pyruvate metabolism of oral sucrose load using dissolution dynamic nuclear polarization. By this technique, metabolic alterations in several different metabolic related diseases and their metabolic treatment responses can be accessed.

Methods

In four healthy pigs the lactate‐to‐pyruvate, alanine‐to‐pyruvate and bicarbonate‐to‐pyruvate ratio was measured following administration of regular cola and consecutive injections of hyperpolarized [1‐13C]pyruvate four times within an hour.

Results

The overall lactate‐to‐pyruvate metabolic profile changed significantly over one hour following an acute sucrose load leading to a significant rise in blood glucose.

Conclusion

The reproducibility of hyperpolarized magnetic resonance spectroscopy in the healthy pig kidney demonstrated a repeatability of more than 94% for all metabolites and, furthermore, that the pyruvate to lactate conversion and the blood glucose level is elevated following endogastric sucrose administration. Magn Reson Med 74:558–563, 2015. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Assessment of intensive care unit‐acquired weakness in young and old mice: An E. coli septic peritonitis model
Authors: Witteveen Esther , Hoogland Inge C.M. , Wieske Luuk , Weber Nina C. , Verhamme Camiel , Schultz Marcus J. , van Schaik Ivo N. , Horn Janneke
Published: May 2015

Introduction: There are few reports of in vivo muscle strength measurements in animal models of ICU‐acquired weakness (ICU‐AW). In this study we investigated whether the Escherichia coli (E. coli) septic peritonitis mouse model may serve as an ICU‐AW model using in vivo strength measurements and myosin/actin assays, and whether development of ICU‐AW is age‐dependent in this model. Methods: Young and old mice were injected intraperitoneally with E. coli and treated with ceftriaxone. Forelimb grip strength was measured at multiple time points, and the myosin/actin ratio in muscle was determined. Results: E. coli administration was not associated with grip strength decrease, neither in young nor in old mice. In old mice, the myosin/actin ratio was lower in E. coli mice at t = 48 h and higher at t = 72 h compared with controls. Conclusions: This E. coli septic peritonitis mouse model did not induce decreased grip strength. In its current form, it seems unsuitable as a model for ICU‐AW. Muscle Nerve 53: 127–133, 2016
Long‐term life expectancy for children with ependymoma and medulloblastoma
Authors: Frandsen Jonathan E. , Wagner Aaron , Bollo Robert J. , Shrieve Dennis C. , Poppe Matthew M.
Published: May 2015

Objectives

There is a paucity of long‐term follow‐up data for children with intracranial ependymoma (IE) and medulloblastoma (MB). What happens to these children 20, 30, or 40 years after diagnosis? Do they have potential for a normal lifespan? The purpose of this study was to ascertain the long‐term survival potential in children with MB or IE who have survived 5 years from diagnosis.

Methods

A retrospective analysis was conducted using the SEER Program. Children (ages 0–19 years) from 1973 to 2011 with a diagnosis of MB or IE were identified. A cohort was created of potentially cured patients who survived 5 years from diagnosis. Cox proportional hazards models and Kaplan–Meier estimates were utilized to analyze long‐term survival.

Results

We identified 876 patients with MB and 474 patients with IE who were alive 5 years from diagnosis. Patients with MB had a 30‐year overall survival (OS) and cancer‐specific survival (CSS) of 70.2% and 80.1%, respectively. Patients with IE had a 30‐year OS and CSS of 57.3% and 68.8%, respectively. When comparing MB with IE, MB had improved CSS (P = 0.04) and trended toward increased OS (P = 0.10).

Conclusions

A significant number of deaths due to disease occur for several decades after treatment for both IE and MB. Despite this, the potential for long‐term survival exists in 5‐year survivors of both histologies. If alive at 5 years from diagnosis, patients with MB tend to have a lower risk of death from disease compared to those with IE. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
Synthesis and characterization of cationic gemini surfactant modified Na–bentonite and its applications for rubber nanocomposites
Authors: Khalaf A.I. , Hegazy M.A. , El‐Nashar D.E.
Published: May 2015

A cationic gemini surfactant (N‐isopropyl‐N, N‐dimethyldodecan 1‐aminium bromide) was synthesized by quaternization reaction. The synthesized surfactant was characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. Modified Na–bentonite (organoclay) was obtained by the intercalation of a gemini surfactant between the layers of sodium bentonite and characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), FTIR, thermogravimetry–differential thermal analysis (TGA–DTA) and differential scanning calorimetry (DSC) techniques. The results of XRD, TEM, FTIR, TGA, and corresponding DSC analysis indicate that gemini surfactant has been successfully intercalated into the clay layers. Rubber‐based nanocomposites have been prepared by incorporating various concentration of organically modified bentonite on to natural rubber/styrene–butadiene rubber (NR/SBR) rubber blend (75/25) using two roll mill. Effect of organoclay content on XRD, curing, mechanical, and scanning electron microscopy (SEM) properties of the nanocomposites are investigated. The morphological study showed the intercalation of nanoclay in NR/SBR blend chain. It was found that the organoclay decrease the optimum and scorch time of the curing reaction, increase maximum torque and the curing rate, which was attributed to the further intercalation during vulcanization process. Mechanical properties such as tensile strength, modulus and elongation at break have improved. POLYM. COMPOS., 38:396–403, 2017. © 2015 Society of Plastics Engineers
Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?
Authors: Alqahtani Saad , Seoane‐Vazquez Enrique , Rodriguez‐Monguio Rosa , Eguale Tewodros
Published: May 2015

Introduction

The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA.

Methods

This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999–2011. Descriptive statistics, t‐tests, and chi‐squared and Wilcoxon tests were performed.

Results

Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies.

Conclusion

Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products. Copyright © 2015 John Wiley & Sons, Ltd.
The economics of counterfeit Avastin: a geospatial and statistical analysis of demographic correlates to FDA warning letters
Authors: Cuomo Raphael E. , Mackey Tim K. , Stigler Paula
Published: May 2015

Purpose

In 2012, the Food and Drug Administration (FDA) sent warning notices to clinics and medical practitioners that may have purchased or administered counterfeited versions of the angiogenesis cancer drug Avastin Genentech, South San Francisco, California, USA. The purpose of this study was to explore potential differences in demographic, economic, and healthcare coverage characteristics between areas that received these counterfeit warning notices and those that did not receive notices. The aims of this study are to improve future counterfeit drug surveillance and better assess potential risk factors associated with counterfeit cancer drugs.

Methods

Addresses for warning notices sent to healthcare practitioners were obtained from the FDA and then geocoded using arcgis. Variables chosen for statistical and geospatial analyses were then identified and assessed based on their potential association with Avastin access and affordability. These variables included demographic and economic factors (percent below the poverty line, percent uninsured, and median household income) and healthcare coverage data (percent Medicare enrollees) available from the US Center for Medicare and Medicaid Services. All variables were analyzed at the US county level.

Results

Our analysis uncovered 401 distinct US counties where the FDA sent at least one counterfeit Avastin warning notice. A hot spot analysis of notices and variables was carried out using arcgis software to identify and visualize risk features with high and low values of clustering. In a multiple logistic regression model reassessing visually observed geospatial associations, the receipt of a notice was not significantly associated with percent uninsured (p = 0.3121), but was significantly associated with percent Medicare enrollees (OR = 0.874 per 10% increase; p = 0.0121), individuals below federal poverty line (OR = 2.990 per 10% increase; p < 0.0001), and median household income (OR = 2.698 per $10 000 increase; p < 0.0001).

Conclusions

Our study found that county‐level economic and demographic factors are potentially associated with counterfeit Avastin warning receipt after controlling for the total number of people residing in each county. These geographic associations indicate that individuals in counties where patients have greater ability to afford more expensive treatment, and consequently where providers can seek higher reimbursement, may have been at higher risk to counterfeit Avastin exposure. These findings can help inform future efforts to improve drug safety surveillance and more proactively identify patients at the highest risk for counterfeit cancer drugs. Copyright © 2015 John Wiley & Sons, Ltd.
Post‐marketing monitoring of intussusception after rotavirus vaccination in Japan
Authors: Bauchau Vincent , Van Holle Lionel , Mahaux Olivia , Holl Katsiaryna , Sugiyama Keiji , Buyse Hubert
Published: May 2015

Purpose

RotarixTM was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that RotarixTM may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and RotarixTM vaccination in Japan.

Methods

All IS cases spontaneously reported post‐vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post‐vaccination) and for each vaccine dose (two doses).

Results

Before January 2013, approximately 601 000 RotarixTM doses were distributed in Japan. For a risk period of 7 days post‐dose 1 and post‐dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed‐to‐expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post‐dose 1 and post‐dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed‐to‐expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively.

Conclusion

A statistically significant excess of IS cases was observed within 7 days post‐dose 1, but not post‐dose 2. These results are consistent with previous observations in large post‐marketing safety studies in other world regions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
Insulin and other antidiabetic drugs and hepatocellular carcinoma risk: a nested case‐control study based on Italian healthcare utilization databases
Authors: Bosetti Cristina , Franchi Matteo , Nicotra Federica , Asciutto Rosario , Merlino Luca , La Vecchia Carlo , Corrao Giovanni
Published: May 2015

Purpose

Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetics.

Methods

We have analyzed the role of various antidiabetic drugs on HCC in a nested case‐control study using the healthcare utilization databases of the Lombardy Region in Italy. This included 190 diabetic subjects with a hospital discharge reporting a diagnosis of malignant HCC and 3772 diabetic control subjects matched to each case on sex, age, date at cohort entry, and duration of follow‐up.

Results

Increased risks of HCC were found for use of insulin (odds ratio [OR] = 3.73, 95% confidence interval [CI] 2.52–5.51), sulfonylureas (OR = 1.39, 95%CI 0.98–1.99), and repaglinide (OR = 2.12, 95%CI 1.38–3.26), while a reduced risk was found for use of metformin (OR = 0.57, 95%CI 0.41–0.79). The risk of HCC increased with increasing duration of insulin use (OR = 2.52 for <1 year, 5.41 for 1–2 years, and 6.01 for ≥2 years; p for trend < 0.001), while no clear pattern with duration was observed for sulfonylureas, repaglinide, and metformin.

Conclusion

Our study supports the evidence that patients with diabetes using metformin, and possibly other antidiabetic drugs that increase insulin sensibility, have a reduced risk of HCC, while those using insulin or drugs that increase circulating insulin, such as insulin secretagogues, have an increased risk. Whether these associations are causal, or influenced by different severity of diabetes and/or possible residual bias or misclassification, is still open to discussion. Copyright © 2015 John Wiley & Sons, Ltd.
Health literacy among pharmacy visitors in the Netherlands
Authors: Koster Ellen S. , Philbert Daphne , Bouvy Marcel L.
Published: May 2015

Purpose

Health literacy is defined as the ability to obtain, understand and apply information to make appropriate health decisions. Most health literacy research has been performed in the USA. Our objective was to study the prevalence of limited health literacy among adult pharmacy visitors in the Netherlands and to assess the association between health literacy and understanding of drug label information.

Methods

A cross‐sectional study was performed in community pharmacies belonging to the Utrecht Pharmacy Practice network for Education and Research. Adult pharmacy visitors (aged ≥18 years) were approached in the pharmacy waiting area and invited for a brief interview including the newest vital sign, a validated health literacy assessment measure and questions about understanding of standard drug label instructions.

Results

A total of 984 pharmacy visitors were included in the study: 63% were women, mean age was 56 years and the majority was of native origin (84%). Based on newest vital sign scores, 52% had limited health literacy skills. Pharmacy visitors with limited health literacy skills had significantly lower understanding of drug label instructions (p < 0.001).

Conclusion

Approximately half of the pharmacy visitors in this study had limited health literacy skills. These individuals experienced more difficulties understanding drug label instructions. These findings emphasize the need to identify patients with limited health literacy skills, as these patients might be at increased risk for drug‐related problems caused by misunderstanding of information. Copyright © 2015 John Wiley & Sons, Ltd.
Post‐traumatic stress disorder symptoms in family caregivers of adult patients with acute leukemia from a dyadic perspective
Authors: Jia Mutian , Li Jie , Chen Chunyan , Cao Fenglin
Published: May 2015

Background

Acute leukemia is a fatal disease in adults that not only affects the patients who suffer from it but also their family caregivers. No studies have investigated post‐traumatic stress disorder symptoms (PTSS) in family caregivers of adult patients with acute leukemia using a matched sample. The current study examined PTSS in adult patients with acute leukemia and their family caregivers and investigated the factors associated with caregivers' PTSS.

Methods

A total of 163 patient–caregiver dyads completed questionnaires assessing their PTSS, psychological resilience, and perceived social support. Hierarchical linear regression was used to explore the related factors of caregivers' PTSS.

Results

More caregivers than patients met caseness criteria for PTSS (36.8% vs. 18.4%, p < 0.001). Among caregivers, being more closely related to the patients (e.g., spouses and parents), having patients with higher PTSS and having lower psychological resilience were independently associated with more severe PTSS.

Conclusions

Caregivers of acute leukemia patients had significantly more severe PTSS than did their patients. This study is the first to investigate PTSS among family caregivers of adult patients with acute leukemia and its related factors in a matched sample. More attention should be paid to the caregivers of patients with acute leukemia to minimize their PTSS and thus improve mental health of caregivers and reduce potential negative consequences for the patients themselves. Copyright © 2015 John Wiley & Sons, Ltd.
Field resistance to the Bacillus thuringiensis protein Cry1Ac expressed in Bollgard® hybrid cotton in pink bollworm, Pectinophora gossypiella (Saunders), populations in India
Authors: Mohan Komarlingam S , Ravi Kadanur C , Suresh Pennadam J , Sumerford Douglas , Head Graham P
Published: May 2015

BACKGROUND

Bollgard® cotton, expressing Cry1Ac insecticidal protein, was approved for commercial planting in India in 2002, and by 2009 constituted 87% of the Indian crop, reducing losses from lepidopteran pests, including pink bollworm (PBW), Pectinophora gossypiella. Inadequate control of PBW in fields of single‐gene Bollgard cotton was reported in 2009; surveys revealed heavy infestations of PBW in Bollgard, restricted to Gujarat state, but not elsewhere in India.

RESULTS

Bioassays of PBW strains from Bollgard bolls showed that, while susceptible PBW could not complete development to third and later instar at 10.0 µg Cry1Ac mL−1, 66.1% of larvae from Gujarat Bollgard strains could. A field‐resistant strain, further selected in the laboratory, had susceptibility to Cry1Ac reduced by >2000‐fold. Resistance to Cry1Ac did not confer cross‐resistance to the Cry2Ab2 protein. In 2010, Bollgard fields in Gujarat continued to be infested with PBW, and many Bollgard fields in the adjoining states of Maharashtra and Madhya Pradesh showed high‐level infestation by PBW.

CONCLUSION

Inadequate planting of refuges for PBW is the likely explanation for the field resistance to Bt cotton observed in Gujarat. These findings underscore the higher vulnerability of single‐gene Bt products relative to dual‐gene products expressing Cry1Ac and Cry2Ab2, and the increased risk of resistance evolution with low refuge compliance. © 2015 Society of Chemical Industry
Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions
Authors: Vanbellingen Quentin P. , Elie Nicolas , Eller Michael J. , Della‐Negra Serge , Touboul David , Brunelle Alain
Published: May 2015

Rationale

In Time‐of‐Flight Secondary Ion Mass Spectrometry (TOF‐SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF‐SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub‐µm lateral resolution, but the combination of both is generally not possible.

Methods

With a TOF‐SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches.

Results

The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass‐to‐charge ratio.

Conclusions

Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF‐SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.