bluuebunny/crossref_metadata_2025 huggingface dataset:
The St Vincent's potentially inappropriate medicines study: development of a disease‐specific consensus list and its evaluation in ambulatory heart failure care
Authors: Bermingham Margaret , Ryder Mary , Travers Bronagh , Edwards Nuala , Lalor Lorraine , Kelly Deirdre , Gallagher Joseph , O'Hanlon Rory , McDonald Kenneth , Ledwidge Mark
Published: August 2014

Aims

Heart failure (HF) patients may be at risk of prescription of potentially inappropriate medicines (PIMs) yet no disease‐specific list is available to assess PIM use in this population. A Consensus Potentially Inappropriate Medicines in Heart Failure (PIMHF) list was developed, assessed, and compared with an established, general tool in an ambulatory HF population.

Methods and results

The Consensus PIMHF list was compiled using modified Delphi methodology with a multidisciplinary team. The list consisted of 11 items. The medication profile of 350 patients was assessed. The association of a Consensus PIMHF item use over a median follow‐up period of 1.8 (interquartile range 1.3–2.1) years with the primary endpoint of death, acute hospitalization, or unscheduled outpatient visit was examined. Fifty‐one patients (14.6%) were prescribed ≥1 Consensus PIMHF item. In univariable analysis, patients prescribed ≥1 Consensus PIMHF item were 58% more likely to experience the primary endpoint than those with none [95% confidence interval (CI) 1.02–2.45]. When adjusted for age, sex, and HF severity, this difference remained [hazard ratio (HR) 1.88, 95% CI 1.16–3.06] and these associations were in contrast to the use of a more general tool (HR 1.24, 95% CI 0.83–1.84). However, when further adjusted to include co‐morbidity score and polypharmacy, there was no association with outcome using either tool (HR 1.40, 95% CI 0.83–2.38; HR 1.05, 95% CI 0.69–1.60, respectively).

Conclusion

The Consensus PIMHF list provides the first HF‐specific medicines review tool. These results provide some support for more disease‐specific tools with limited lists of PIMs to rationalize medicines management in HF. However, more prospective work on the application of these tools in practice is needed.
Effect of variety and processing method on functional properties of traditional sweet potato flour (“elubo”) and sensory acceptability of cooked paste (“amala”)
Authors: Fetuga Ganiyat , Tomlins Keith , Henshaw Folake , Idowu Michael
Published: August 2014

“Amala” is a generic term in Nigeria, used to describe a thick paste prepared by stirring flour (“elubo”) from yam, cassava or unripe plantain, in hot water, to form a smooth consistency. In order to overcome its high perishability and increase the utilization of sweet potato roots, three varieties of sweet potato roots were processed into flour using two methods. The interactive effect of variety and the processing method had a significant effect (P < 0.05) on all the functional properties of the flour except yellowness, setback viscosity, and peak time. Acceptable sweet potato “amala” with average sensory acceptability score of 7.5 were obtained from yellow‐fleshed varieties irrespective of the processing method. Flour that produced acceptable “amala” were characterized by lower values of protein (2.20–3.94%), fiber (1.30–1.65%), total sugar (12.41–38.83 μg/mg), water absorption capacity (168–215 g/100 g), water solubility (8.29–14.65%), swelling power (0.52–0.82 g/g), and higher peak time (6.9–8.7 min).
The role of epigenetics in cognitive ageing
Authors: Mather Karen A. , Kwok John B. , Armstrong Nicola , Sachdev Perminder S.
Published: August 2014

Objective

As the population is ageing, a better understanding of the underlying causes of age‐related cognitive decline (cognitive ageing) is required. Epigenetic dysregulation is proposed as one of the underlying mechanisms for cognitive ageing. We review the current knowledge on epigenetics and cognitive ageing and appraise the potential of epigenetic preventative and therapeutic interventions.

Design

Articles on cognitive ageing and epigenetics in English were identified.

Results

Epigenetic dysregulation occurs with cognitive ageing, with changes in histone post‐translational modifications, DNA methylation and non‐coding RNA reported. However, human studies are lacking, with most being cross‐sectional using peripheral blood samples. Pharmacological and lifestyle factors have the potential to change aberrant epigenetic profiles; but few studies have examined this in relation to cognitive ageing.

Conclusions

The relationship between epigenetic modifications and cognitive ageing is only beginning to be investigated. Epigenetic dysregulation appears to be an important feature in cognitive ageing, but whether it is an epiphenomenon or a causal factor remains to be elucidated. Clarification of the relationship between epigenetic profiles of different cell types is essential and would determine whether epigenetic marks of peripheral tissues can be used as a proxy for changes occurring in the brain. The use of lifestyle and pharmacological interventions to improve cognitive performance and quality of life of older adults needs more investigation. Copyright © 2014 John Wiley & Sons, Ltd.
Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation
Authors: Nagai Shunji , Yoshida Atsushi , Facciuto Marcelo , Moonka Dilip , Abouljoud Marwan S. , Schwartz Myron E. , Florman Sander S.
Published: August 2014

Although experimental evidence has indicated that ischemia‐reperfusion (I/R) injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of I/R injury on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion (VI) because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (range, 40 days‐4.6 years). Cumulative recurrence curves according to cold ischemia time (CIT) at 2‐hour intervals and warm ischemia time (WIT) at 10‐minute intervals showed that CIT >10 hours and WIT >50 minutes were associated with significantly increased recurrence (P = 0.015 and 0.036, respectively). Multivariate Cox's regression analysis identified prolonged cold (>10 hours; P = 0.03; hazard ratio [HR] = 1.9) and warm (>50 minutes; P = 0.003; HR = 2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors, including poor differentiation, micro‐ and macrovacular invasion, exceeding Milan criteria, and alpha‐fetoprotein >200 ng/mL. Prolonged CIT (P = 0.04; HR = 2.24) and WIT (P = 0.001; HR = 5.1) were also significantly associated with early (within 1 year) recurrence. In the subgroup analysis, prolonged CIT (P = 0.01; HR = 2.6) and WIT (P = 0.01; HR = 3.23) were independent risk factors for recurrence in patients with VI, whereas there was no association between ischemia times and HCC recurrence in patients with no VI. Conclusion: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors. (Hepatology 2015;61:895–904)
Characterization of hepatitis C virus intergenotypic recombinant strains and associated virological response to sofosbuvir/ribavirin
Authors: Hedskog Charlotte , Doehle Brian , Chodavarapu Krishna , Gontcharova Viktoria , Crespo Garcia Javier , De Knegt Robert , Drenth Joost P.H , McHutchison John G. , Brainard Diana , Stamm Luisa M. , Miller Michael D. , Svarovskaia Evguenia , Mo Hongmei
Published: August 2014

To date, intergenotypic recombinant hepatitis C viruses (HCVs) and their treatment outcomes have not been well characterized. This study characterized 12 novel HCV recombinant strains and their response to sofosbuvir in combination with ribavirin (SOF/RBV) treatment. Across the phase II/III studies of SOF, HCV samples were genotyped using both the Siemens VERSANT HCV Genotype INNO‐LiPA 2.0 Assay (Innogenetics, Ghent, Belgium) and nonstructural (NS)5B sequencing. Among these patient samples, genotype assignment discordance between the two methods was found in 0.5% of all cases (12 of 2,363), of which all were identified as genotype 2 by INNO‐LiPA (12 of 487; 2.5%). HCV full‐genome sequences were obtained for these 12 samples by a sequence‐independent amplification method coupled with next‐generation sequencing. HCV full‐genome sequencing revealed that these viruses were recombinant HCV strains, with the 5' part corresponding to genotype 2 and the 3' part corresponding to genotype 1. The recombination breakpoint between genotypes 2 and 1 was consistently located within 80 amino acids of the NS2/NS3 junction. Interestingly, one of the recombinant viruses had a 34‐amino‐acid duplication at the location of the recombination breakpoint. Eleven of these twelve patients were treated with a regimen for genotype 2 HCV infection, but responded as if they had genotype 1 infection; 1 patient had received placebo. Conclusion: Twelve new HCV intergenotypic recombinant genotype 2/1 viruses have been characterized. The antiviral response to a 12‐ to 16‐week course of SOF/RBV treatment in these patients was more similar to responses among genotype 1 patients than genotype 2 patients, consistent with their genotype 1 NS5B gene (Hepatology 2015;61:471‐480)
A dual‐task design of corrosion‐controlling and osteo‐compatible hexamethylenediaminetetrakis‐ (methylene phosphonic acid) (HDTMPA) coating on magnesium for biodegradable bone implants application
Authors: Zhao Sheng , Chen Yingqi , Liu Bo , Chen Meiyun , Mao Jinlong , He Hairuo , Zhao Yuancong , Huang Nan , Wan Guojiang
Published: August 2014

Magnesium as well as its alloys appears increasingly as a revolutionary bio‐metal for biodegradable implants application but the biggest challenges exist in its too fast bio‐corrosion/degradation. Both corrosion‐controllable and bio‐compatible Mg‐based bio‐metal is highly desirable in clinic. In present work, hexamethylenediaminetetrakis (methylenephosphonic acid) [HDTMPA, (H2O3P−CH2)2−N−(CH2)6−N−(CH2−PO3H2)2], as a natural and bioactive organic substance, was covalently immobilized and chelating‐deposited onto Mg surface by means of chemical conversion process and dip‐coating method, to fullfill dual‐task performance of corrosion‐protective and osteo‐compatible functionalities. The chemical grafting of HDTMPA molecules, by participation of functional groups on pretreated Mg surface, ensured a firmly anchored base layer, and then sub‐sequential chelating reactions of HDTMPA molecules guaranteed a homogenous and dense HDTMPA coating deposition on Mg substrate. Electrochemical corrosion and immersion degradation results reveal that the HDTMPA coated Mg provides a significantly better controlled bio‐corrosion/degradation behavior in phosphate buffer saline solution as compared with untreated Mg from perspective of clinic requirement. Moreover, the HDTMPA coated Mg exhibits osteo‐compatible in that it induces not only bioactivity of bone‐like apatite precipitation but also promotes osteoblast cells adhesion and proliferation. Our well‐controlled biodegradable and biocompatible HDTMPA modified Mg might bode well for next generation bone implant application. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1640–1652, 2015.
Development of wheat glutenin nanoparticles and their biodistribution in mice
Authors: Reddy Narendra , Shi Zhen , Xu Helan , Yang Yiqi
Published: August 2014

Wheat glutenin nanoparticles intended for targeted drug delivery were biocompatible and were detected in the kidney, liver, and spleen in mice. Protein‐based nanoparticles are preferred for therapeutic drug and gene delivery owing to their biocompatibility and ability to load various types of drugs. However, proteins such as a collagen and albumin are unstable in aqueous environments and are not ideal for drug delivery applications. Wheat glutenin has been demonstrated to be biocompatible and have good stability under aqueous conditions. Films and fibers have been made from wheat glutenin for medical applications but there are no reports on developing micro‐ or nanoparticles. In this research, wheat glutenin nanoparticles (70–140 nm) were prepared and the stability of the nanoparticles under various physiological conditions was investigated. Nanoparticles were fluorescently labeled and later injected into mice and the ability of the nanoparticles to penetrate into the cells in various organs was studied. Strong acidic or alkaline conditions provided glutenin nanoparticles with low diameters and the particles were more stable under the pH 7 rather than pH of 4. Glutenin nanoparticles were predominantly found in the liver in mice. Our in vivo and in vitro studies suggest that glutenin nanoparticles are suitable for drug delivery applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1653–1658, 2015.
The effect of calcium phosphate composite scaffolds on the osteogenic differentiation of rabbit dental pulp stem cells
Authors: Ling Ling E. , Feng Lin , Liu Hong‐Chen , Wang Dong‐Sheng , Shi Zhan‐Ping , Wang Jun‐Cheng , Luo Wei , Lv Yan
Published: August 2014

The objective of this study is to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation, and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano‐hydroxyapatite/collagen/poly (l‐lactide) (nHAC/PLA), imitating the composition and the micro‐structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta‐tricalcium phosphate (β‐TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio‐lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severely combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM‐treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM‐treated DPSCs. The absorption water rate and protein adsorption rate of nHAC/PLA was significantly higher than β‐TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto β‐TCP; and the proliferation rate of the cells was also significantly higher than that of β‐TCP on 1, 3, and 7 days of cell culture. The ALP activity, calcium/phosphorus content and mineral formation of DPSCs + β‐TCP were significantly higher than DPSCs + nHAC/LA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β‐TCP alone, DPSCs + nHAC/PLA and DPSCs + β‐TCP, and this three groups displayed increased bone formation over the 12‐week period. The percentage of total bone formation area had no difference between DPSCs + β‐TCP and DPSCs + nHAC/PLA at each time point, but the percentage of mature bone formation area of DPSCs + β‐TCP was significantly higher than that of DPSCs + nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation, and that the DPSCs on β‐TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs + β‐TCP group. These findings have provided a further knowledge that scaffold architecture has different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs + β‐TCP construct. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part: 103A: 1732–1745, 2015.
Collagen scaffolds combined with collagen‐binding ciliary neurotrophic factor facilitate facial nerve repair in mini‐pigs
Authors: Lu Chao , Meng Danqing , Cao Jiani , Xiao Zhifeng , Cui Yi , Fan Jingya , Cui Xiaolong , Chen Bing , Yao Yao , Zhang Zhen , Ma Jinling , Pan Juli , Dai Jianwu
Published: August 2014

The preclinical studies using animal models play a very important role in the evaluation of facial nerve regeneration. Good models need to recapitulate the distance and time for axons to regenerate in humans. Compared with the most used rodent animals, the structure of facial nerve in mini‐pigs shares more similarities with humans in microanatomy. To evaluate the feasibility of repairing facial nerve defects by collagen scaffolds combined with ciliary neurotrophic factor (CNTF), 10‐mm‐long gaps were made in the buccal branch of mini‐pigs' facial nerve. Three months after surgery, electrophysiological assessment and histological examination were performed to evaluate facial nerve regeneration. Immunohistochemistry and transmission electron microscope observation showed that collagen scaffolds with collagen binding (CBD)‐CNTF could promote better axon regeneration, Schwann cell migration, and remyelination at the site of implant device than using scaffolds alone. Electrophysiological assessment also showed higher recovery rate in the CNTF group. In summary, combination of collagen scaffolds and CBD‐CNTF showed promising effects on facial nerve regeneration in mini‐pig models. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1669–1676, 2015.
IL‐1β Induces p62/SQSTM1 and Represses Androgen Receptor Expression in Prostate Cancer Cells
Authors: Chang M.A. , Patel V. , Gwede M. , Morgado M. , Tomasevich K. , Fong E.L. , Farach‐Carson M.C. , Delk Nikki A.
Published: August 2014

Chronic inflammation is associated with advanced prostate cancer (PCa), although the mechanisms governing inflammation‐mediated PCa progression are not fully understood. PCa progresses to an androgen independent phenotype that is incurable. We previously showed that androgen independent, androgen receptor negative (AR−) PCa cell lines have high p62/SQSTM1 levels required for cell survival. We also showed that factors in the HS‐5 bone marrow stromal cell (BMSC) conditioned medium can upregulate p62 in AR+ PCa cell lines, leading us to investigate AR expression under those growth conditions. In this paper, mRNA, protein, and subcellular analyses reveal that HS‐5 BMSC conditioned medium represses AR mRNA, protein, and nuclear accumulation in the C4‐2 PCa cell line. Using published gene expression data, we identify the inflammatory cytokine, IL‐1β, as a candidate BMSC paracrine factor to regulate AR expression and find that IL‐1β is sufficient to both repress AR and upregulate p62 in multiple PCa cell lines. Immunostaining demonstrates that, while the C4‐2 population shows a primarily homogeneous response to factors in HS‐5 BMSC conditioned medium, IL‐1β elicits a strikingly heterogeneous response; suggesting that there are other regulatory factors in the conditioned medium. Finally, while we observe concomitant AR loss and p62 upregulation in IL‐1β‐treated C4‐2 cells, silencing of AR or p62 suggests that IL‐1β regulates their protein accumulation through independent pathways. Taken together, these in vitro results suggest that IL‐1β can drive PCa progression in an inflammatory microenvironment through AR repression and p62 induction to promote the development and survival of androgen independent PCa. J. Cell. Biochem. 115: 2188–2197, 2014. © 2014 Wiley Periodicals, Inc.
Clinical drug‐drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P‐glycoprotein
Authors: Robertson Sarah M. , Luo Xia , Dubey Neeraj , Li Chonghua , Chavan Ajit B. , Gilmartin Geoffrey S. , Higgins Mark , Mahnke Lisa
Published: August 2014

Ivacaftor is approved in the USA for the treatment of cystic fibrosis (CF) in patients with a G551D‐CFTR mutation or one of eight other CFTR mutations. A series of in vitro experiments conducted early in the development of ivacaftor indicated ivacaftor and metabolites may have the potential to inhibit cytochrome P450 (CYP) 2C8, CYP2C9, CYP3A, and CYP2D6, as well as P‐glycoprotein (P‐gp). Based on these results, a series of clinical drug‐drug interaction (DDI) studies were conducted to evaluate the effect of ivacaftor on sensitive substrates of CYP2C8 (rosiglitazone), CYP3A (midazolam), CYP2D6 (desipramine), and P‐gp (digoxin). In addition, a DDI study was conducted to evaluate the effect of ivacaftor on a combined oral contraceptive, as this is considered an important comedication in CF patients. The results indicate ivacaftor is a weak inhibitor of CYP3A and P‐gp, but has no effect on CYP2C8 or CYP2D6. Ivacaftor caused non‐clinically significant increases in ethinyl estradiol and norethisterone exposure. Based on these results, caution and appropriate monitoring are recommended when concomitant substrates of CYP2C9, CYP3A and/or P‐gp are used during treatment with ivacaftor, particularly drugs with a narrow therapeutic index, such as warfarin.
Alpha‐lipoic acid andN‐acetylcysteine protects intensive swimming exercise‐mediated germ‐cell depletion, pro‐oxidant generation, and alteration of steroidogenesis in rat testis
Authors: Jana Kuladip , Dutta Ananya , Chakraborty Pratip , Manna Indranil , Firdaus Syed Benazir , Bandyopadhyay Debasish , Chattopadhyay Ratna , Chakravarty Baidyanath
Published: August 2014

Prolonged and strenuous exercise has been proposed as a possible source of male‐factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α‐lipoic acid andN‐acetylcysteine (NAC) on intensive swimming‐induced germ‐cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra‐testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm‐head abnormalities increased. Western‐blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse‐transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose‐6‐phosphate dehydrogenase, glutathione peroxidase, glutathione S‐transferase, and caspase‐3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha‐lipoic acid and NAC supplementation prevented the swimming‐induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ‐cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co‐administration of α‐lipoic acid and NAC.Mol. Reprod. Dev. 81: 833–850, 2014. © 2014 Wiley Periodicals, Inc.
A Comparison of the Temperature Regime of Short Stream Segments under Forested and Non‐Forested Riparian Zones at Eleven Sites Across North America
Authors: Simmons J. A. , Anderson M. , Dress W. , Hanna C. , Hornbach D. J. , Janmaat A. , Kuserk F. , March J. G. , Murray T. , Niedzwiecki J. , Panvini D. , Pohlad B. , Thomas C. , Vasseur L.
Published: August 2014

When forested riparian zones are cleared for agriculture or development, major changes can occur in the stream temperature regime and consequently in ecosystem structure and function. Our main objective was to compare the summer temperature regimes of streams with and without forest canopy cover at multiple sites. The secondary objective was to identify the components of the stream heat budget that had the greatest influence on the stream temperature regime. Paired stream reaches (one forested and one non‐forested or ‘open’) were identified at 11 sites distributed across the USA and Canada. Stream temperature was monitored at the upstream and downstream ends of 80 to 130‐m‐long reaches during summer, and five variables were calculated to describe the stream temperature regime. Overall, compared with forested reaches, open reaches tended to have significantly higher daily mean (mean difference = 0.33 ± 1.1°C) and daily maximum (mean difference = 1.0 ± 1.7°C) temperatures and wider daily ranges (mean difference = 1.1 ± 1.7°C). Mean and maximum daily net heat fluxes in open reaches tended to be greater (or less negative) than those in forested reaches. However, certain sites showed the opposite trends in some variables because of the following: (i) Daily mean and maximum temperatures were biased by differences in inflow temperature between paired reaches and (ii) inputs of cold groundwater exerted a strong influence on temperature. Modelling and regression results suggested that within sites, differences in direct solar radiation were mainly responsible for the observed differences in stream temperature variables at the daily scale. © 2014 The Authors.River Research and Applicationspublished by John Wiley & Sons, Ltd.
FISH BODY CONDITION AND RECRUITMENT RESPONSES TO ANTECEDENT FLOWS IN DRYLAND RIVERS ARE SPECIES AND RIVER SPECIFIC
Authors: Balcombe S. R. , Arthington A. H. , Sternberg D.
Published: August 2014

Dryland rivers in arid and semi‐arid regions drain approximately one‐third of the Earth's land area, yet basic aspects of their ecology are poorly documented and many are threatened by excessive water use leading to alterations of the flow regime. Management of dryland rivers imperilled by changes to the flow regime requires quantitative hydro‐ecological relationships and models to support environmental flow restoration strategies and to define ecological response indicators for assessment of trends in ecological health. Fish living in dryland rivers experience highly variable levels of food resources associated with ‘boom and bust’ productivity patterns driven by highly irregular episodes of rainfall, runoff and floodplain inundation followed by busts associated with drying of remnant aquatic habitats. To cope with variable food resource levels, fish store energy as fat during productivity booms, enabling them to breed later or to survive through extended periods of limited food resources. This study tracked temporal patterns of body condition and recruitment success of the four most abundant fish species in two Australian dryland river systems with contrasting patterns of flow variability, Cooper Creek and the Moonie River. We found consistent responses to flow magnitude and timing for body condition and/or recruitment success in Cooper Creek but fewer responses in the Moonie River. Results suggest that the fish metrics and relationships to flow established for Cooper Creek may apply in similar dryland rivers exhibiting clear boom and bust patterns, whereas the Moonie River results could be applicable to rivers with less variable flow patterns and fewer spells of zero flows. Our study demonstrates that simple, non‐destructive methods based on fish length and weight provide useful biological indicators of response to flow variability provided that care is taken with species selection and that hydro‐ecological relationships are calibrated for each contrasting type of hydrologic regime. Copyright © 2014 John Wiley & Sons, Ltd.
Characterization of nitride‐based LED materials and devices using TOF‐SIMS
Authors: Wei Xuecheng , Zhao Lixia , Wang Junxi , Zeng Yiping , Li Jinmin
Published: August 2014

Nitride‐based light‐emitting diodes (LEDs) have been developed significantly in terms of both fundamental understanding as well as application, but there are still many new challenges, such as the droop effects and reliability issues, which hinder further progress. SIMS is an important technique and has been widely used to monitor the doping concentrations in the LED multilayers and characterize the layer interface qualities. However, most of them are performed by magnetic sector‐based instruments. In this study, we measured layer structures for nitride‐based LED epilayers using time‐of‐flight SIMS. By changing different surface qualities, the primary ion raster sizes, the oxygen partial pressures, and the optimized conditions to achieve better LED depth profiles were obtained, under which the super lattice structures of AlGaN/GaN and the modulation of Mg atom concentrations can also be clearly distinguished. Copyright © 2014 John Wiley & Sons, Ltd.
Are Clinical Trials With Mesenchymal Stem/Progenitor Cells too Far Ahead of the Science? Lessons From Experimental Hematology
Authors: Prockop Darwin J. , Prockop Susan E. , Bertoncello Ivan
Published: August 2014

The cells referred to as mesenchymal stem/progenitor cells (MSCs) are currently being used to treat thousands of patients with diseases of essentially all the organs and tissues of the body. Strikingly positive results have been reported in some patients, but there have been few prospective controlled studies. Also, the reasons for the beneficial effects are frequently unclear. As a result there has been a heated debate as to whether the clinical trials with these new cell therapies are too far ahead of the science. The debate is not easily resolved, but important insights are provided by the 60-year history that was required to develop the first successful stem cell therapy, the transplantation of hematopoietic stem cells. The history indicates that development of a dramatically new therapy usually requires patience and a constant dialogue between basic scientists and physicians carrying out carefully designed clinical trials. It also suggests that the field can be moved forward by establishing better records of how MSCs are prepared, by establishing a large supply of reference MSCs that can be used to validate assays and compare MSCs prepared in different laboratories, and by continuing efforts to establish in vivo assays for the efficacy of MSCs. Stem Cells  2014;32:3055–3061
A Switch From Canonical to Noncanonical Wnt Signaling Mediates Early Differentiation of Human Neural Stem Cells
Authors: Bengoa-Vergniory Nora , Gorroño-Etxebarria Irantzu , González-Salazar Itxaso , Kypta Robert M.
Published: August 2014

Wnt/β-catenin signaling is essential for neurogenesis but less is known about β-catenin-independent Wnt signals. We show here that Wnt/activator protein-1 (AP-1) signaling drives differentiation of human embryonic stem cell and induced pluripotent stem cell-derived neural progenitor cells. Neuronal differentiation was accompanied by a reduction in β-catenin/Tcf-dependent transcription and target gene expression, increased levels and/or phosphorylation of activating transcription factor 2 (ATF2), cyclic AMP response element-binding protein, and c-Jun, and increased AP-1-dependent transcription. Inhibition of Wnt secretion using the porcupine inhibitors IWP-2 and Wnt-C59 blocked neuronal differentiation, while activation or inhibition of Wnt/β-catenin signaling had no effect. Neuronal differentiation increased expression of several Wnt genes, including WNT3A, silencing of which reduced differentiation. Addition of recombinant Wnt-3a to cells treated with IWP-2 or Wnt-C59 increased AP-1 levels and restored neuronal differentiation. The effects of Wnt-3a could not be blocked by addition of Dkk-1 or IWR-1, suggesting the involvement of noncanonical signaling. Consistent with this, restoration of neuronal differentiation by Wnt-3a was reduced by inhibition of Jun N-terminal kinase (JNK) and by gene silencing of ATF2. Together, these observations suggest that β-catenin-independent Wnt signals promote neural stem/progenitor cell differentiation in a signaling pathway involving Wnt-3a, JNK, and ATF2. Stem Cells  2014;32:3196–3208
Concise Review: Exploring miRNAs—Toward a Better Understanding of Hematopoiesis
Authors: Hong Seok-Ho , Kim Kye-Seong , Oh Il-Hoan
Published: August 2014

Hematopoiesis is governed by a multidimensional regulatory network involving both intrinsic and extrinsic factors that control self-renewal and differentiation of hematopoietic stem cells (HSCs) through the coordination of influences that affect cell fate. Increasing evidence indicates that microRNAs (miRNAs), short noncoding RNAs of approximately 22 nucleotides, play a central role in orchestrating these regulatory mechanisms to modulate the multiple entities of hematopoietic function in a cell-type specific manner, including self-renewal, lineage commitment, and survival of HSCs as well as their microenvironmental crosstalk. Here, we summarize the current understanding regarding the regulatory effects of miRNA on hematopoietic cells, thus enlightening their role in fine-tuning HSC function and hematopoietic homeostasis. Stem Cells  2015;33:1–7
Design of composite slabs with prepressed embossments using small‐scale tests
Authors: Holomek Josef , Bajer Miroslav , Barnat Jan , Schmid Pavel
Published: August 2014

The loadbearing capacity of steel‐concrete composite slabs using thin‐walled steel sheeting with prepressed embossments is in most cases determined by their resistance in longitudinal shear. The design of composite slabs still requires full‐scale laboratory bending tests to be performed. Small‐scale shear tests cannot include all of the influences affecting the bent slab. However, by using an appropriate procedure, the shear characteristics obtained from such tests can be used to determine the bending capacity of the slab. Two such procedures are compared in this paper.

End restraints effectively increase the loadbearing capacity of the composite slabs. Two different types of easily assembled additional end constraints are also tested and compared in this paper. Small‐scale tests are used to obtain their shear bearing characteristics and to predict the loadbearing capacity of bent slabs using these restraints.
Innovation and Transaction Cost
Authors: Suematsu Chihiro
Published: August 2014

Innovation is indispensable to increase sales through matching new market needs and new technologies, in order to revitalize the saturated economy. This is a significant issue shared among the developed countries. However, it is difficult to define innovation because its meaning tends to be taken widely due to its versatile importance. The classic definition of innovation advocated by Joseph A. Schumpeter back in 1934 is used in almost every study on the topic. Innovation, according to Schumpeter, is “a new combination of means of production—that is, as a change in the factors of production (inputs) to produce products (outputs).”
Transaction Interface: Organization, Process, and System
Authors: Suematsu Chihiro
Published: August 2014

The preceding chapter described how transaction costs are incurred at transaction interfaces. This chapter will illustrate that organizational functions are essentially synonymous with transaction interfaces. From this perspective, both strategy and IT can be handled identically as organizational issues. Modularity, standards, and innovation management are also included and discussed in the following chapters. In this book, new universal management methodologies to deal with organizational and strategic issues are proposed applying this perspective.
Coevolution of Markets and Organizations
Authors: Suematsu Chihiro
Published: August 2014

In this book, the commonalities of organizations and the market,1 in both of which the transaction is executed in compliance with the transaction interface, have been emphasized. In economics, Ronald Coase clarified in Chap. 1 of his epoch-making book The Firm, the Market, and the Law2 that “markets are institutions that exist to facilitate exchange—that is, they exist in order to reduce the cost of carrying out exchange transactions.” This could be paraphrased, using the terminologies of this book, as “the market is a collection of interfaces to reduce transaction costs.” That is, both the organization and the market are collections of interfaces with an identical purpose.
Methodologies for Designing and Managing Interfaces, Modules, Standards, and Processes
Authors: Suematsu Chihiro
Published: August 2014

Throughout this book, the essential commonalities among organizations—interfaces,1 modules, and standards—have been explored. Module structure is determined by interfaces rather than the module body. A standard is defined as a condition under which interfaces are shared by the majority. Processes correspond to interfaces per se. For these managerial devices, which are essentially identical, common design methodologies should be applied. As discussed thus far in this book, transaction costs are reduced by the development of interfaces, but the results would be very different depending upon the technologies of the design and operation of interfaces.
Logical Thinking/Creative Thinking
Authors: Suematsu Chihiro
Published: August 2014

In this chapter, creativity will be examined and structured from the perspective of transaction. Just as in the previous chapters, the enhancement of the creative thinking process and activity will be studied by applying the methodology of managing transaction costs. It is obvious that the methodology of integration of modules based on interfaces also has significant value in creativity, which is widely conceived as integration of knowledge. In addition, the development and enhancement of individual creative thinking will be analyzed from a perspective that it is also conceived as diversified communication within an individual’s intellectual activity.
Preservation of the Left Gastric Artery on the Basis of Anatomical Features in Patients Undergoing Distal Pancreatectomy with Celiac Axis En‐bloc Resection (DP‐CAR)
Authors: Okada Ken‐ichi , Kawai Manabu , Tani Masaji , Hirono Seiko , Miyazawa Motoki , Shimizu Atsushi , Kitahata Yuji , Yamaue Hiroki
Published: August 2014

Background

The incidence of delayed gastric emptying (DGE) is high in patients undergoing distal pancreatectomy with celiac axis en‐bloc resection (DP‐CAR).

Methods

The medical records of 37 consecutive patients who underwent DP‐CAR were evaluated for the incidence of DGE in 23 patients (62 %) with left gastric artery (LGA)‐resecting DP‐CAR (conventional DP‐CAR) compared with 14 patients (38 %) who underwent distal pancreatectomy with resection of the common hepatic artery and splenic artery, with preservation of the LGA (modified DP‐CAR) for pancreatic carcinoma. The patients with tumors situated more than 10 mm away from the antecedent branching LGA underwent modified DP‐CAR.

Results

Antecedent branching of the LGA was found in 19 patients (51 %) in this series. In the conventional DP‐CAR group, the LGA was involved in 20 patients (87.0 %). The International Study Group of Pancreatic Surgery (ISGPS) grades for the conventional DP‐CAR group were as follows: no DGE = 43 %, grade A = 26 %, B = 13 %, and C = 17 %. In the modified DP‐CAR group, they were as follows: no DGE = 93 %, grade A = 7 %, and grade B/C = 0 %. The R0 rate was higher in the modified DP‐CAR group (79 %) than in the conventional DP‐CAR group (43 %) (p = 0.048). Univariate analyses revealed resection of LGA, residual tumor status (R1), and clinically relevant (Grade B, C) pancreatic fistula increased the risk of DGE. On multivariate analysis, resection of the LGA was an independent risk factor for increased incidence of DGE.

Conclusion

Modified DP‐CAR, when it is feasible, significantly reduces the incidence of DGE in comparison with conventional DP‐CAR.
Anterior Surgical Treatment of Cervical Spondylotic Myelopathy
Authors: Quinn John C. , Kiely Paul D. , Lebl Darren R. , Hughes Alexander P.
Published: August 2014

Background

Cervical spondylotic myelopathy (CSM) is a common indication for cervical spine surgery. Surgical options include anterior, posterior, or combined procedures each with specific advantages and disadvantages.

Questions/Purposes

This article will provide a description of the various anterior alternatives and discuss the available evidence used in guiding the surgical decision making process with the aim of answering the following questions: (1) What anatomical/disease related factors favor anterior over posterior surgeries? (2) What are the common anterior procedures and how safe and effective are they? (3) What are the most effective options for multilevel CSM? (4) Is there a role for motion preservation? An additional objective is to discuss technical advances that have improved success rates for anterior procedures.

Methods

The PubMed database was searched. Keywords were CSM and anterior surgery. Three hundred eighty two articles were found one hundred three were reviewed. Articles describing anterior cervical techniques were selected along with studies describing the various anterior techniques or comparisons of anterior to posterior techniques.

Results

Anterior decompression and fusion procedures are more effective than posterior procedures for patients with primarily ventrally located compression especially in the presence of cervical kyphosis. ACDF, ACCF, and hybrid combinations are safe and effective treatment options for multilevel CSM. Anterior procedures may be more cost effective and result in significantly improved postoperative quality of life and health-related quality of life measures compared to posterior procedures.

Conclusion

Anterior cervical decompression techniques are safe and effective in the treatment of CSM. Anterior surgeries may be preferable to posterior approaches, when considering health-related quality of life measures and cost effectiveness.
An Interesterified Palm Olein Test Meal Decreases Early‐Phase Postprandial Lipemia Compared to Palm Olein: a Randomized Controlled Trial
Authors: Hall Wendy L. , Fiuza Brito Marcela , Huang Junlan , Wood Lucy V. , Filippou Androulla , Sanders Thomas A. B. , Berry Sarah E. E.
Published: August 2014

Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn‐2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high‐fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40–70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double‐blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6‐h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95 % CI 1.01–2.29) compared to NPO (iAUC 2.33 mmol/L h, 95 % CI 1.58–3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4–6 h were slightly reduced following IPO compared to NPO [NPO−IPO mean difference 0.29 mmol/L (95 % CI −0.01–0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn‐2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.
Distribution of Glycolipid and Unsaturated Fatty Acids in Human Hair
Authors: Takahashi Toshie , Yoshida Satoshi
Published: August 2014

It has been recognized that human hair lipids play crucial roles in the integrity of cells and matrices, while the details of distribution and structure of the minor lipids are hardly known. Here we investigated the lipids at the hair surface, at the interface between cuticle and cortex and in the interior of hair (cortex, medulla and melanin granules). Hair lipids and fatty acids and their metabolites were detected and characterized by using infrared spectroscopy and several mass spectrometry techniques (FTIR, ToF–SIMS, GCMS, and ESI–MS). As a result, it was found that unsaturated fatty acids were present more in the cortex of hair than at the hair surface. At the interface between cuticle and cortex, it is suggested that steryl glycoside‐like lipids containing N‐acetylglucosamine were present, and contributing to the adhesion between the cuticle and cortex of hair. Oxidative metabolites derived from integral fatty acids such as linoleic and alpha‐linolenic acids were found in the hair bulb and melanin granules. Especially the oxidative metabolites of alpha‐linolenic acid were integrated into the lipids non‐covalently and tightly bound to melanin granules (namely, melanin lipids) and suggested as being involved in the biosynthetic processes of melanosome.
CK2 accumulation at the axon initial segment depends on sodium channel Nav1
Authors: Hien Y.E. , Montersino A. , Castets F. , Leterrier C. , Filhol O. , Vacher H. , Dargent B.
Published: August 2014

Accumulation of voltage‐gated sodium channel Nav1 at the axon initial segment (AIS), results from a direct interaction with ankyrin G. This interaction is regulated in vitro by the protein kinase CK2, which is also highly enriched at the AIS. Here, using phosphospecific antibodies and inhibition/depletion approaches, we showed that Nav1 channels are phosphorylated in vivo in their ankyrin‐binding motif. Moreover, we observed that CK2 accumulation at the AIS depends on expression of Nav1 channels, with which CK2 forms tight complexes. Thus, the CK2–Nav1 interaction is likely to initiate an important regulatory mechanism to finely control Nav1 phosphorylation and, consequently, neuronal excitability.
Cloning and functional expression in E. coli of a polyphenol oxidase transcript from Coreopsis grandiflora involved in aurone formation
Authors: Kaintz Cornelia , Molitor Christian , Thill Jana , Kampatsikas Ioannis , Michael Claudia , Halbwirth Heidi , Rompel Annette
Published: August 2014

Polyphenol oxidases are involved in aurone biosynthesis but the gene responsible for 4‐deoxyaurone formation in Asteraceae was so far unknown. Three novel full‐length cDNA sequences were isolated from Coreopsis grandiflora with sizes of 1.80 kb (cgAUS1) and 1.85 kb (cgAUS2a, 2b), encoding for proteins of 68–69 kDa, respectively. cgAUS1 is preferably expressed in young petals indicating a specific role in pigment formation. The 58.9 kDa AUS1 holoproenzyme, was recombinantly expressed in E. coli and purified to homogeneity. The enzyme shows only diphenolase activity, catalyzing the conversion of chalcones to aurones and was characterized by SDS–PAGE and shot‐gun type nanoUHPLC–ESI‐MS/MS.
A rapid quantitative activity assay shows that the Vibrio cholerae colonization factor GbpA is an active lytic polysaccharide monooxygenase
Authors: Loose Jennifer S.M. , Forsberg Zarah , Fraaije Marco W. , Eijsink Vincent G.H. , Vaaje-Kolstad Gustav
Published: August 2014

The discovery of the copper‐dependent lytic polysaccharide monooxygenases (LPMOs) has revealed new territory for chemical and biochemical analysis. These unique mononuclear copper enzymes are abundant, suggesting functional diversity beyond their established roles in the depolymerization of biomass polysaccharides. At the same time basic biochemical methods for characterizing LPMOs, such as activity assays are not well developed. Here we describe a method for quantification of C1‐oxidized chitooligosaccharides (aldonic acids), and hence LPMO activity. The method was used to quantify the activity of a four‐domain LPMO from Vibrio cholerae, GbpA, which is a virulence factor with no obvious role in biomass processing.