bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlorotoxin: Structure, activity, and potential uses in cancer therapy
Authors: Ojeda Paola G. , Wang Conan K. , Craik David J.
Published: September 2015

Chlorotoxin is a disulfide‐rich stable peptide from the venom of the Israeli scorpion Leiurus quinquestriatus, which has potential therapeutic applications in the treatment of cancer. Its ability to preferentially bind to tumor cells has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has attracted interest as a vehicle to deliver anti‐cancer drugs specifically to cancer cells. Given its interesting structural and biological properties, chlorotoxin also has the potential to be used in a variety of other biotechnology and biomedical applications. Here, we review the structure, activity and potential applications of chlorotoxin as a drug design scaffold. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 25–36, 2016.
Direct production of functional matrix metalloproteinase—14 without refolding or activation and its application for in vitro inhibition assays
Authors: Nam Dong Hyun , Ge Xin
Published: September 2015

Human matrix metalloproteinase (MMP)‐14, a membrane‐bound zinc endopeptidase, is one of the most important cancer targets because it plays central roles in tumor growth and invasion. Large amounts of active MMP‐14 are required for cancer research and the development of chemical or biological MMP‐14 inhibitors. Current methods of MMP‐14 production through refolding and activation are labor‐intensive, time‐consuming, and often associated with low recovery rates, lot‐to‐lot variation and heterogeneous products. Here, we report direct production of the catalytic domain of MMP‐14 in the periplasmic space ofEscherichia coli. 0.5 mg/L of functional MMP‐14 was produced without tedious refolding or problematic activation process. MMP‐14 prepared by simple periplasmic treatment can be readily utilized to evaluate the potencies of chemical and antibody‐based inhibitors. Furthermore, co‐expression of both MMP‐14 and antibody Fab fragments in the periplasm facilitated inhibitory antibody screening by avoiding purification of MMP‐14 or Fabs. We expect this MMP‐14 expression strategy can expedite the development of therapeutic drugs targeting MMPs with biological significance. Biotechnol. Bioeng. 2016;113: 717–723. © 2015 Wiley Periodicals, Inc.
Engineering of high yield production of L‐serine in Escherichia coli
Authors: Mundhada Hemanshu , Schneider Konstantin , Christensen Hanne Bjerre , Nielsen Alex Toftgaard
Published: September 2015

L‐serine is a widely used amino acid that has been proposed as a potential building block biochemical. The high theoretical yield from glucose makes a fermentation based production attractive. In order to achieve this goal, serine degradation to pyruvate and glycine in E. coli MG1655 was prevented by deletion of three L‐serine deaminases sdaA, sdaB, and tdcG, as well as serine hydroxyl methyl transferase (SHMT) encoded by glyA. Upon overexpression of the serine production pathway, consisting of a feedback resistant version of serA along with serB and serC, this quadruple deletion strain showed a very high serine production yield (0.45 g/g glucose) during small‐scale batch fermentation in minimal medium. Serine, however, was found to be highly toxic even at low concentrations to this strain, which lead to slow growth and production during fed batch fermentation, resulting in a serine production of 8.3 g/L. The production strain was therefore evolved by random mutagenesis to achieve increased tolerance towards serine. Additionally, overexpression of eamA, a cysteine/homoserine transporter was demonstrated to increase serine tolerance from 1.6 g/L to 25 g/L. During fed batch fermentation, the resulting strain lead to the serine production titer of 11.7 g/L with yield of 0.43 g/g glucose, which is the highest yield reported so far for any organism. Biotechnol. Bioeng. 2016;113: 807–816. © 2015 Wiley Periodicals, Inc.
Real‐Time Intracellular Mg2+ Signaling and Wave Propagation by Subdiffraction‐Limit Super‐Resolution Microscopy
Authors: Chakkarapani Suresh Kumar , Lee Seungah , Lee Gwang , Kang Seong Ho
Published: September 2015

Magnesium ion (Mg2+) is an important intracellular component that plays a fundamental role in many cellular processes. The super‐localization of intracellular Mg2+ signaling and wave propagation in a single cell with subdiffraction‐limit image resolution is demonstrated for the first time by direct stochastic optical reconstruction microscopy (dSTORM). Mag‐fluo‐4‐AM, an intracellular Mg2+ fluorescent indicator dye, is used for the fluorescence imaging of intracellular Mg2+ in human embryonic kidney 293 (HEK‐293) cells as a model. Mag‐fluo‐4‐AM is photoswitched between its fluorescent and dark states and the resulting super‐resolution cell image reveals uniform and specific labeling of Mg2+ with thousands of fluorophores per cell and localization precision of 21 ± 1 nm. Furthermore, the real‐time dynamics of Mg2+ wave propagation are studied by dSTORM. The sparks and waves show random temporal propagation patterns in nonhomogeneous substructures with 0.2 s time intervals. Thus, dSTORM allows characterization of intracellular processes at sub‐nanometre spatial resolution with high temporal resolution.
Site‐Specific Antibody Labeling by Covalent Photoconjugation of Z Domains Functionalized for Alkyne–Azide Cycloaddition Reactions
Authors: Perols Anna , Arcos Famme Melina , Eriksson Karlström Amelie
Published: September 2015

Antibodies are extensively used in research, diagnostics, and therapy, and for many applications the antibodies need to be labeled. Labeling is typically performed by using amine‐reactive probes that target surface‐exposed lysine residues, resulting in heterogeneously labeled antibodies. An alternative labeling strategy is based on the immunoglobulin G (IgG)‐binding protein domain Z, which binds to the Fc region of IgG. Introducing the photoactivable amino acid benzoylphenylalanine (BPA) into the Z domain makes it possible for a covalent bond to be be formed between the Z domain and the antibody on UV irradiation, to produce a site‐specifically labeled product. Z32BPA was synthesized by solid‐phase peptide synthesis and further functionalized to give alkyne‐Z32BPA and azide‐Z32BPA for CuI‐catalyzed cycloaddition, as well as DBCO‐Z32BPA for Cu‐free strain‐promoted cycloaddition. The Z32BPA variants were conjugated to the human IgG1 antibody trastuzumab and site‐specifically labeled with biotin or fluorescein. The fluorescently labeled trastuzumab showed specific staining of the membranes of HER2‐expressing cells in immunofluorescence microscopy.
How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives
Authors: Sherstyuk Yuliya V. , Abramova Tatyana V.
Published: September 2015

The fundamental roles of nucleoside triphosphates and nucleotide cofactors such as NAD+ in biochemistry are well known. In recent decades, continuing research has revealed the key role of 5′‐capped RNA and 5′,5′‐dinucleoside polyphosphates in the regulation of vitally important physiological processes. Last but not least, the commercial potential of nucleoside triphosphate synthesis can hardly be overestimated. Nevertheless, despite decades of investigation and the obvious topicality of the research on the chemical synthesis of the nucleotide compounds containing phosphate anhydride linkages, none of the existing procedures can be considered an up‐to‐date “gold standard”. However, there are a number of fruitful synthetic approaches to forming phosphate anhydride linkages in satisfactory yield. These are summarized in this concise review, organized by the type of active phosphorous intermediate and reagents used.
Visible Light Excitable SCN− Selective Fluorescence Probe Derived from Thiophene
Authors: Das Sudipta , Lohar Sisir , Matalobos Jesús Sanmartín , Das Debasis
Published: September 2015

An efficient fluorescence probe, 4‐methyl‐2,6‐bis((thiophen‐2‐ylmethylimino)methyl)phenol (DFPTMA) and its SCN− adduct has been synthesized and characterized by different spectroscopic techniques like 1H NMR,13C NMR, QTOF‐MS ES+, UV‐Vis and FTIR spectroscopy. Single crystal X‐ray structure of DFPTMA is reported. In presence of SCN−, DFPTMA exhibits significant fluorescence enhancement (λEx, 455 nm, λEm, 504 nm) in aqueous methanol (water‐methanol, 1:4, V/V, 0.1 mol/L HEPES buffer, pH 7.4). Common bio‐relevant anions viz. CH3COO−, NO2−, NO3−, Cl−, Br−, I−, SO42−, HSO4−, N3−, HAsO42−, Cr2O72−, H2PO4−, ClO4−, NCO−, CN−, CO32−, F−, PO43−, S2−, HS− do not interfere in the recognition of SCN−. Lowest detection limit for SCN− is 0.88 µmol/L with response time <5 min. The SCN− assisted enhancement in emission intensity may be attributed to the formation of H‐bond which enhances the rigidity of the molecular assembly.
Influence of the Inner Diameters of Capillary on the Z‐Pinch Plasma of the Capillary Discharge Soft x‐ray Laser
Authors: Jiang Shan , Zhao Yong‐peng , Cui Huai‐yu , Li Lian‐bo , Ding Yu‐jie , Zhang Wen‐hong , Li Wei
Published: September 2015

In this paper, the effects of inner diameters on the Z‐pinch plasma of capillary discharge soft x‐ray laser were investigated with the 3.2 mm and 4.0 mm inner diameter alumina capillaries. The intensities of the laser emitted from the 3.2 mm and 4.0 mm inner diameter alumina capillaries were measured under different initial pressures. To understand the underlying physics of the experimental measurements, the Z‐pinch plasma simulations had been conducted with a one‐dimensional cylindrical symmetry Lagrangian magneto‐hydrodynamics (MHD) code. The parametric studies of Z‐pinch plasma, such as the electron temperature, the electron density and the Ne‐like Ar ion density, were performed with the MHD code. With the experimental and the simulated results, the discussions had been conducted on the Z‐pinch plasma of Ne‐like Ar 46.9 nm laser with the 3.2 mm and 4.0 mm inner diameter alumina capillaries. The analysis had been made on the difference of the gain coefficients under the optimum pressures with both capillaries. Then, the effects of inner diameters on the optimum pressure and the pressure domain were analyzed. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electron Temperatures and Electron Densities in Microwave Helium Discharges with Pressures Higher than 0.1 MPa
Authors: Sasaki K. , Soma S. , Akashi H. , ElSabbagh M. , Ikeda Y.
Published: September 2015

We adopted laser Thomson scattering for measuring the electron density and the electron temperature of microwave plasmas produced in helium at the pressures higher than the atmospheric pressure. The electron density decreased while we observed the increase in the electron temperature with the pressure. These are reasonable results by considering the decrease in the reduced electric field, the dominant loss of electrons via three‐body recombination with helium as the third body, and the production of electrons with medium energy via heavy particle collisions at the high gas pressure. The temporal variation of the electron temperature had the rise and the fall time constants of approximately 10 ns. The rapid heating and cooling of the electron temperature are due to the fast energy transfer from electrons to helium because of the high collision frequency in the high‐pressure discharge. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Collisionless Damping of Geodesic Acoustic Mode in a Multi‐Ion Plasma with Superthermal Ions
Authors: Ni G. S. , Liu Y. , Liu S. Q.
Published: September 2015

The dispersion relation of geodesic acoustic mode is investigated in a multi‐ion toroidal plasma on the basis of linear gyrokinetic equations where ions are assumed to take a nonextensive distribution. It is found that the frequency of GAM becomes larger with the decrease of q. Consequently, GAM will damp more rapidly. The effective charge corresponding to the maximum damping rate is found to move towards unity as q decreases. As indicates that in a plasma with superthermal bulk ions, the influence of the impurity ion on the damping rate is weakened. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Energy‐aware cooperative and distributed channel estimation schemes for wireless sensor networks
Authors: Ning Zhaolong , Song Qingyang , Yu Yao , Lv Yujuan , Wang Xing , Kong Xiangjie
Published: September 2015

It is a fact that energy consumption is a key issue in wireless sensor networks. In order to improve the energy efficiency of network utilization, distributed power control methods are advocated. However, the sensors are deployed randomly, which results in the channel gains that are difficult to be obtained; thus, how to estimate channel gains accurately to increase node communication efficiency and reduce energy consumption is the motivation of our work. In this paper, a cooperative and distributed algorithm based on diffusion least mean square (LMS) is firstly proposed to estimate channel gain by utilizing the equality and collaboration of sensor nodes. Its objective is to enhance the accuracy and convergence of the estimation process. Because the presented globe‐based scheme is unrealistic for practical utilization, two distributed estimation algorithms are investigated for different network scenarios, namely, exchange diffusion combine LMS and exchange combine diffusion LMS. Simulation results demonstrate the effectiveness of our methods. Copyright © 2015 John Wiley & Sons, Ltd.
Prevalence of hypertriglyceridemic waist and association with risk of type 2 diabetes mellitus: a meta‐analysis
Authors: Ren Yongcheng , Luo Xinping , Wang Chongjian , Yin Lei , Pang Chao , Feng Tianping , Wang Bingyuan , Zhang Lu , Li Linlin , Yang Xiangyu , Zhang Hongyan , Zhao Jingzhi , Hu Dongsheng
Published: September 2015

Introduction

A meta‐analysis of studies assessing the prevalence of hypertriglyceridemic waist and an association with risk of type 2 diabetes mellitus (T2DM).

Materials and methods

PubMed, EMBASE, Web of Science, CNKI, CQVIP and Wanfang databases were searched for studies of the prevalence of hypertriglyceridemic waist or association with risk of T2DM. Reference lists of each original article were also searched. A random‐effects model was used to synthesize the combined prevalence and odds ratios. Publication bias and substantial heterogeneity were examined.

Results

Twenty‐five eligible studies involving 93 194 participants (93 194 for prevalence and 34 199 for odds ratios): 17 articles of prevalence, and 8 of both prevalence and risk of T2DM. Prevalence of hypertriglyceridemic waist ranged from 4% to 47%, with pooled prevalence of 18% (95% CI 13–23%), overall: 18% (95% CI 13–23%) for men and 19% (95% CI 13–24%) for women. Odds ratios ranged from 2.8 to 9.6 for T2MD in overall, with pooled odds ratios of 4.18 (95% CI 3.55–4.92), overall: 3.55 (95% CI 2.93–4.31) for men and 4.18 (95% CI 3.43–5.09) for women.

Discussion/conclusion

The prevalence of hypertriglyceridemic waist has reached an alarming level and is closely associated with increased risk of T2DM in the general population, particularly among women and among brown‐skinned men and women. Copyright © 2015 John Wiley & Sons, Ltd.
An evidence‐based review of systemic treatments for itch
Authors: Pongcharoen P. , Fleischer A.B.
Published: September 2015

Background and objective

Many treatment modalities are used for itch treatment in daily medical practices without adequate evidence of their efficacy. The purpose of this study was to provide an evidence‐based review of the literature as to the clinical benefits of systemic anti‐itch treatments.

Databases and data treatment

We performed a systematic review and, when appropriate, meta‐analysis from available placebo‐controlled randomized controlled trails (RCTs). A systematic search of the literature was performed using Pub Med, Cochrane Library and EMBASE. The primary outcome was the change in the itch score comparing the intervention group and placebo group. The meta‐analysis method was used to calculate the pooled outcome of each treatment modality.

Results

Twenty‐six eligible RCTs were included. We found evidence for the effectiveness of: naltrexone (in cholestatic itch and atopic eczema), nalfurafine (in uraemic itch), gabapentin (in uraemic itch) and ursodeoxycholic acid (in intrahepatic cholestasis of pregnancy). The results of two RCTs with naltrexone in uremic itch are conflicting. On the other hand, we did not find any benefit from ondansetron (in cholestatic and uraemic itch), ergocalciferol (in uraemic itch), colesevelam (in cholestatic itch) or gabapentin (in cholestatic itch). The possible effectiveness of sertraline, paroxetine, cromolyn sodium, zinc sulphate, omega‐3 fatty acid, montelukast, doxepin and rifampin need to be confirmed from future large studies, because the available evidence is insufficient.

Conclusions

The findings from this study suggest the effective therapeutic approaches for itch. The major limitations are that there are small numbers of available RCTs and methodological differences across studies.
Evolving understanding on the aetiology of thermally provoked itch
Authors: Murota H. , Katayama I.
Published: September 2015

Background and objectives

Itch is one of the major symptoms in dermatology clinics, and severely impairs the quality of life. Itch is frequently produced by environmental stimuli, especially heat or warmth. Changes of temperature on the skin surface and noxious heat stimuli augment and develop itch, respectively. Thermally provoked itch is sometimes intractable with existing treatments.

Data bases and data treatment

Recent researches, linking heat sensation and itch, were searched in MEDLINE literature database through PubMed.

Results

Recent studies of the transient receptor potential cation channel subfamily vanilloid type 1 (TRPV1), the calcitonin gene‐related peptide (CGRP) and the vesicular glutamate transporter 2 (VGLUT2), which link noxious heat and itch, contribute to a much better understanding of the thermally evoked itch process. From a clinical perspective, a warm sensation is a major provocative factor for subjects with atopic dermatitis. The accumulation of artemin (also known as enovin or neublastin) in the dermis of lesional skin can possibly provide a pathological mechanism for warmth‐provoked itch.

Conclusions

This mini‐review describes recent results of both basic and clinical research related to thermally provoked itch.
Screening of microorganisms from Antarctic surface water and cytotoxicity metabolites from Antarctic microorganisms
Authors: Zheng Lanhong , Yang Kangli , Liu Jia , Sun Mi , Zhu Jiancheng , Lv Mei , Kang Daole , Wang Wei , Xing Mengxin , Li Zhao
Published: September 2015

The Antarctic is a potentially important library of microbial resources and new bioactive substances. In this study, microorganisms were isolated from surface water samples collected from different sites of the Antarctic. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay‐based cytotoxicity‐tracking method was used to identify Antarctic marine microorganism resources for antitumor lead compounds. The results showed that a total of 129 Antarctic microorganism strains were isolated. Twelve strains showed potent cytotoxic activities, among which a Gram‐negative, rod‐shaped bacterium, designated as N11‐8 was further studied. Phylogenetic analysis based on 16S rRNA gene sequence showed that N11‐8 belongs to the genus Bacillus. Fermented active products of N11‐8 with molecular weights of 1–30 kDa had higher inhibitory effects on different cancaer cells, such as BEL‐7402 human hepatocellular carcinoma cells, U251 human glioma cells, RKO human colon carcinoma cells, A549 human lung carcinoma cells, and MCF‐7 human breast carcinoma cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. Microscopic observations showed that the fermented active products have inhibitory activity on BEL‐7402 cells similar to that of mitomycin C. Further studies indicated that the fermented active products have high pH and high thermal stability. In conclusion, most strains isolated in this study may be developed as promising sources for the discovery of antitumor bioactive substances. The fermented active products of Antarctic marine Bacillus sp. N11‐ 8 are expected to be applied in the prevention and treatment of cancer.
Phasic stabilization of motor output after auditory and visual distractors
Authors: Piitulainen Harri , Bourguignon Mathieu , Smeds Eero , De Tiège Xavier , Jousmäki Veikko , Hari Riitta
Published: September 2015

To maintain steady motor output, distracting sensory stimuli need to be blocked. To study the effects of brief auditory and visual distractors on the human primary motor (M1) cortex, we monitored magnetoencephalographic (MEG) cortical rhythms, electromyogram (EMG) of finger flexors, and corticomuscular coherence (CMC) during right‐hand pinch (force 5–7% of maximum) while 1‐kHz tones and checkerboard patterns were presented for 100 ms once every 3.5–5 s. Twenty‐one subjects (out of twenty‐two) showed statistically significant ∼20‐Hz CMC. Both distractors elicited a covert startle‐like response evident in changes of force and EMG (∼50% of the background variation) but without any visible movement, followed by ∼1‐s enhancement of CMC (auditory on average by 75%, P < 0.001; visual by 33%, P < 0.05) and rolandic ∼20‐Hz rhythm (auditory by 14%, P < 0.05; visual by 11%, P < 0.01). Directional coupling of coherence from muscle to the M1 cortex (EMG→MEG) increased for ∼0.5 s at the onset of the CMC enhancement, but only after auditory distractor (by 105%; P < 0.05), likely reflecting startle‐related proprioceptive afference. The 20‐Hz enhancements occurred in the left M1 cortex and were for the auditory stimuli preceded by an early suppression (by 7%, P < 0.05). Task‐unrelated distractors modulated corticospinal coupling at ∼20 Hz. We propose that the distractors triggered covert startle‐like responses, resulting in proprioceptive afference to the cortex, and that they also transiently disengaged the subject's attention from the fine‐motor task. As a result, the corticospinal output was readjusted to keep the contraction force stable. Hum Brain Mapp 36:5168–5182, 2015. © 2015 Wiley Periodicals, Inc.
Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process
Authors: Ponsioen Cyriel Y. , Chapman Roger W. , Chazouillères Olivier , Hirschfield Gideon M. , Karlsen Tom H. , Lohse Ansgar W. , Pinzani Massimo , Schrumpf Erik , Trauner Michael , Gores Gregory J.
Published: September 2015

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end‐stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. Conclusion: At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. (Hepatology 2016;63:1357–1367)
Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2‐deficient mice
Authors: Zhou Mei , Learned R. Marc , Rossi Stephen J. , DePaoli Alex M. , Tian Hui , Ling Lei
Published: September 2015

Defects in multidrug resistance 3 gene (MDR3), which encodes the canalicular phospholipid flippase, cause a wide spectrum of cholangiopathy phenotypes in humans. Mice deficient in Mdr2 (murine ortholog of MDR3) develop liver diseases that closely reproduce the biochemical, histological, and clinical features of human cholangiopathies such as progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. We hypothesized that modulating bile acid metabolism by the gut hormone fibroblast growth factor 19 (FGF19) may represent a novel approach for treating cholangiopathy and comorbidities. We introduced adeno‐associated virus carrying the gene for either the endocrine hormone FGF19 or engineered FGF19 variant M70 to 12‐week old Mdr2‐deficient mice with fully established disease. Effects on serum levels of liver enzymes, liver histology, and bile acid homeostasis were evaluated. FGF19 and M70 rapidly and effectively reversed liver injury, decreased hepatic inflammation, attenuated biliary fibrosis, and reduced cholecystolithiasis in Mdr2‐deficient mice. Mechanistically, FGF19 and M70 significantly inhibited hepatic expression of Cyp7a1 and Cyp27a1, which encode enzymes responsible for the rate‐limiting steps in the classic and alternate bile acid synthetic pathways, thereby reducing the hepatic bile acid pool and blood levels of bile acids. Importantly, prolonged exposure to FGF19, but not M70, led to the formation of hepatocellular carcinomas in the Mdr2‐deficient mice. Furthermore, M70 ameliorated the hepatosplenomegaly and ductular proliferation that are associated with cholangiopathy. Conclusion: These results demonstrate the potential for treating cholangiopathy by safely harnessing FGF19 biology to suppress bile acid synthesis. (Hepatology 2016;63:914–929)
Toxicity of Tributyltin in Juvenile Common Carp (Cyprinus Carpio): Physiological Responses, Hepatic Gene Expression, and Stress Protein Profiling
Authors: Li Zhi‐Hua , Zhong Li‐Qiao , Mu Wei‐Na , Wu Yan‐Hua
Published: September 2015

In this study, the effects of tributyltin (TBT) on biochemical parameters (antioxidant responses and Na+‐K+‐ATPase) in different tissues were investigated by using juvenile common carp (Cyprinus Carpio) as well as growth and ion regulation–related genes expression and stress‐related proteins profiling in fish liver. Oxidative stress indices and Na+‐K+‐ATPase showed tissues‐specific responses in fish exposed to different TBT concentrations. All tested genes related to GH/IGF‐I axis and ion‐regulation were significantly induced in the TBT group with lower concentrations (except for the igfbp3 in 10 μg/L) and were inhibited in 20 μg/L. In addition, the profiling of two proteins Hsp 70 and MT were increasing in a dose‐dependent manner under TBT stress. In short, TBT‐induced biochemical and molecular responses in different tissues were reflected in the measured parameters in the test. On the basis of TBT residue levels in the natural environment, more long‐term experiments at lower concentrations will be necessary in the future.
The Existence of Well‐Balanced Triple Systems
Authors: Wei Hengjia , Ge Gennian , Colbourn Charles J.
Published: September 2015

A triple system is a collection ofbblocks, each of size three, on a set ofvpoints. It isj‐balanced when every twoj‐sets of points appear in numbers of blocks that are as nearly equal as possible, and well balanced when it isj‐balanced for each. Well‐balanced systems arise in the minimization of variance in file availability in distributed file systems. It is shown that when a triple system that is 2‐balanced and 3‐balanced exists, so does one that is well balanced. Using known and new results on variants of group divisible designs, constructions for well‐balanced triple systems are developed. Using these, the spectrum of pairsfor which such a well‐balanced triple system exists is determined completely.
A Facile Synthesis of 5‐Phenyl‐Dibenzo[b, g][1,8]Napthyridines
Authors: Sampathkumar Natarajan , Murugesh Arumugam , Rajendran Subramaniam Parameswaran
Published: September 2015

The Vilsmeier Haack heterocyclization of 2‐aryl amino‐4‐phenyl quinolines quinoline yielded the hitherto unknown 5‐phenyl‐dibenzo[b,g][1,8]naphthyridines in quantitative yield. The synthesis of aryl amines was achieved by the action of anilines on 2‐chloro‐4‐phenyl quinoline, which in turn was sourced through the combes reaction of benzoyl acetanilides.
No hospital left behind? Education policy lessons for value‐based payment in healthcare
Authors: Maurer Kristin A. , Ryan Andrew M.
Published: September 2015

Value‐based payment systems have been widely implemented in healthcare in an effort to improve the quality of care. However, these programs have not broadly improved quality, and some evidence suggests that they may increase inequities in care. No Child Left Behind is a parallel effort in education to address uneven achievement and inequalities. Yet, by penalizing the lowest performers, No Child Left Behind's approach to accountability has led to a number of unintended consequences. This article draws lessons from education policy, arguing that financial incentives should be designed to support the lowest performers to improve quality. Journal of Hospital Medicine 2016;11:62–64. © 2015 Society of Hospital Medicine
Striving for optimal care: Updates in quality, value, and patient experience
Authors: Moriates Christopher , Mourad Michelle
Published: September 2015

BACKGROUND

Hospitalists are playing a growing role in quality improvement efforts, and they are increasingly spearheading programs to improve patient experience and healthcare value. We aimed to summarize and critique recent research related to quality, value, and patient experience in the clinical practice of hospital medicine.

METHODS

We reviewed articles published between January 2014 and February 2015, identified through a hand search of leading journals, continuing medical education collaborative journal reviews, Agency for Healthcare Research and Quality's Patient Safety network, and PubMed. The authors collectively selected 9 articles based on their relevance to hospital practice. We review their findings, strengths, and limitations and make recommendations for practice. This is a summary of an update we presented at the 2015 Hospital Medicine national meeting.

RESULTS

Key findings include: a comprehensive hand‐off program was associated with improved patient safety; successful readmissions interventions were resource‐intensive, multifaceted and increased patient capacity to handle illness; patient activation was correlated with lower resource use post‐hospitalization; positive associations exist between patient experience and understanding of their hospitalization; hospitals and practitioners can adopt simple low‐cost strategies to reduce the trauma of hospitalization; hospitalists frequently order low‐value tests, most often to reassure themselves or their patients; broad‐spectrum antibiotics are grossly overused in hospitalized patients leading to preventable harms including clostridium difficile colitis, and programs that support “self‐stewardship” may help moderate this risk.

CONCLUSIONS

Recent research provides important insights into readmissions prevention, patient experience and low‐value test ordering, as well as introduces interventions that may mitigate the risks of handoffs and the overuse of broad‐spectrum antibiotics. Journal of Hospital Medicine 2016;11:145–150. © 2015 Society of Hospital Medicine
The role of informed consent in patient complaints: Reducing hidden health system costs and improving patient engagement through shared decision making
Authors: Posner Karen L. , Severson Julie , Domino Karen B.
Published: September 2015

Introduction

Patient complaints about physicians are strongly associated with malpractice risk. Physicians at high risk for lawsuits tend to have poor communication skills and are more commonly the subject of patient complaints about communication issues. If a malpractice action does not arise, patient complaints nonetheless represent significant prelitigation transaction costs for the healthcare system that have not been previously quantified. Informed consent complaints represent a unique constellation of clinical communication skills clearly tied to malpractice risk. The goal of this study was to measure institutional resource consumption allocated to informed consent (IC) complaints, which are both costly and preventable.

Methods

We compared IC complaints to other complaints about medical care in a single medical center in the United States, estimating the absolute and relative burden of IC deficiencies within this healthcare system.

Results

Resource consumption for the resolution of IC complaints far exceeded their proportional representation of complaints, representing half of all complaints, while disproportionately absorbing two‐thirds of staff time devoted to complaint resolution.

Conclusions

Complaint resolution represents an unrecognized remediable cost and an underappreciated opportunity for reducing waste in healthcare. We suggest that healthcare systems can reduce costs and elevate their patient‐centered care practices by improving patient‐provider communication during medical decision making via engagement strategies such as shared decision making.
Oily waste containing natural radionuclides: does it cause stimulation or inhibition of soil bacterial community?
Authors: Galitskaya Polina , Gumerova Raushaniya , Ratering Stefan , Schnell Sylvia , Blagodatskaya Evgenia , Selivanovskaya Svetlana
Published: September 2015

Contamination with oily wastes containing natural radionuclides is a potential hazard for soil health and function. Our study aimed to reveal both structural and functional changes of the microbial community resistant to and able to decompose oily wastes in soil. To do this, we determined CO2 efflux, microbial biomass (by the extraction‐fumigation method), and community structure (by PCR‐SSCP) for 120 d after application of radioactive oily wastes to the soil at the ratio 1:4. The addition of the waste resulted in an increase of the activity concentration of 226Ra by 130 times (up to 643 Bq kg−1) and of 232Th by 29 times (up to 254 Bq kg−1). The calculated weighted dose for the radionuclide 226Ra was found to be below the values that are known to affect microorganisms. However, the cumulative effect of a repeated deposition of radioactive oily waste may result in an increase of the weighted dose up to an effective level. During the incubation, the hydrocarbon (HC) content of the waste‐treated soil decreased from 156 to 54 g kg−1 of soil indicating intensive decomposition of added organics by soil microorganisms. The waste application, however, led to an inhibition of soil microbial biomass compared with the control (by 26–47%). Microbial respiration was stimulated in the first month of incubation and then decreased until the end of the incubation period (by up to 74% compared to the control). The qCO2 was estimated to be 3‐fold higher than the control on day 1 of incubation and equal to the control on day 120 of incubation. The bacterial diversity decreased in the contaminated soil compared with the control soil. The bacterial community structure was altered by domination of new oil degrader species belonging to the genera Dyella, Pseudoxanthomonas, Sinobacter, and Parvibaculum. Thus, disposal of radioactive petroleum waste strongly altered the structure of the microbial community resulting in the selection of resistant species able to decompose pollutants and also affected the community function (inhibition of microbial biomass and stimulation of respiration) which tended to stabilize after long‐term incubation.
Phytogenic pigments in animal nutrition: potentials and risks
Authors: Faehnrich Bettina , Lukas Brigitte , Humer Elke , Zebeli Qendrim
Published: September 2015

Phytogenic pigments are secondary plant compounds responsible for coloring effects in plant tissues. In particular, phenolic flavonoids and terpenoid carotenoids, but also rare compounds like curcumin and betalain, form this group of biochemical agents used in animal nutrition. From the perspective of ecological mutuality between plants and animals, these compounds are of crucial importance because they serve as visual attraction for herbivores but also signal nutritional and/or health‐promoting values. This review focuses on the properties of phytogenic pigments which are likely to impact feed intake and preferences of livestock. Also natural prophylactic and/or therapeutic properties and, in particular, the potential of pigments to enhance quality and health value of animal products for human consumption are important issues. Nevertheless, reasonable limits of use due to possible adverse indications have been suggested recently. Pathways of digestion, metabolism and excretion in animals play a crucial role not only in the evaluation of effectiveness but also in the prediction of potential risks for human consumption. The popularity of natural feed additives is growing; therefore, more research work is needed to better understand metabolic pathways in the animal's body and to better estimate the potentials and risks of pigmenting plant compounds used in animal nutrition. © 2015 Society of Chemical Industry
CD44 single nucleotide polymorphism and isoform switching may predict gastric cancer recurrence
Authors: Suenaga Masaya , Yamada Suguru , Fuchs Bryan C. , Fujii Tsutomu , Kanda Mitsuro , Tanaka Chie , Kobayashi Daisuke , Fujiwara Michitaka , Tanabe Kenneth K. , Kodera Yasuhiro
Published: September 2015

Background and Objectives

The clinical implications of single nucleotide polymorphisms (SNPs) in CD44 remain unclear. This study examined the relationships of CD44 SNPs with clinicopathological parameters and prognosis in Japanese gastric cancer patients.

Methods

The CD44 SNPs were analyzed in 11 gastric cancer cell lines and 517 clinical specimens. The expression of CD44 standard (CD44s) and CD44 variant 9 isoform (CD44v9) transcripts were measured by quantitative real‐time polymerase chain reaction.

Results

The CD44 rs187116 A/A, A/G, and G/G genotypes were present in 10.3%, 45.1%, and 44.7% of patients, respectively. The presence of CD44 rs187116 A/G or G/G genotypes was significantly associated with positive peritoneal washing cytology (P = 0.012). Disease‐free survival of patients with these genotypes was significantly worse than in those with the A/A genotype (P = 0.039). Multivariate analysis showed that the CD44 rs187116 was independently prognostic of disease‐free survival (P = 0.047). The CD44s/CD44v9 ratio was significantly lower in patients with the CD44 rs187116 A/A genotype than in those with the A/G (P = 0.046) and G/G (P = 0.047) genotypes.

Conclusions

The CD44 rs187116 genotype could predict disease recurrence in Japanese gastric cancer patients, and the SNP was associated with CD44 isoform switching. J. Surg. Oncol. 2015;112:622–628. © 2015 Wiley Periodicals, Inc.
Improvements in the Child‐Rearing Attitudes of Latina Mothers Exposed to Interpersonal Trauma Predict Greater Maternal Sensitivity Toward Their 6‐Month‐Old Infants
Authors: Waters Sara F. , Hagan Melissa J. , Rivera Luisa , Lieberman Alicia F.
Published: September 2015

The current study investigated maternal sensitivity in a treatment‐seeking sample of predominately Latina, low‐income pregnant women with histories of interpersonal trauma exposure. Pregnant women (N = 52; M = 27.08 years, SD = 5.66) who enrolled in a study of a perinatal adaptation of child–parent psychotherapy reported on their posttraumatic stress symptoms and child‐rearing attitudes at baseline and again at 6‐months postpartum. Maternal sensitivity was measured via observational coding of a free‐play episode at 6‐months postpartum. Two thirds of mothers exhibited healthy levels of maternal sensitivity, M > 4.0 (range = 2.5–7.0). The results of multiple linear regression predicting maternal sensitivity, R2 = .26, indicated that greater improvements in child‐rearing attitudes over the course of treatment predicted higher levels of maternal sensitivity, β = .33, whereas improvements in posttraumatic stress symptoms over the course of treatment did not, β = −.10. Mothers’ attitudes regarding parenting during the perinatal period may be a mechanism by which intervention fosters healthy mother–infant relationship dynamics. Thus, parenting attitudes are a worthy target of intervention in vulnerable families.
Homoclinic solutions for a class of fourth‐order difference equations
Authors: Shi Haiping , Liu Xia , Zhang Yuanbiao
Published: September 2015

In this paper, a class of fourth‐order nonlinear difference equation is considered. By making use of the critical point theory, we establish various sets of sufficient conditions for the existence of homoclinic solutions and give some new results. One of our results generalizes and improves the results in the literature. Copyright © 2015 John Wiley & Sons, Ltd.
On the decay rates of Timoshenko system with second sound
Authors: Apalara Tijani A. , Messaoudi Salim A. , Keddi Ahmed A.
Published: September 2015

In this work, we study the well‐posedness and the asymptotic stability of a one‐dimensional linear thermoelastic Timoshenko system, where the heat conduction is given by Cattaneo's law and the coupling is via the displacement equation. We prove that the system is exponentially stable provided that the stability number χτ=0. Otherwise, we show that the system lacks exponential stability. Furthermore, in the latter case, we show that the solution decays polynomially. Copyright © 2015 John Wiley & Sons, Ltd.
Economic analyses of stress urinary incontinence surgical procedures in women
Authors: Rawlings Tanner , Zimmern Philippe E.
Published: September 2015

Introduction

To evaluate the quality of economic analysis (EA) of surgical procedures for stress urinary incontinence (SUI) in women.

Methods

A MEDLINE search on EA for SUI surgical procedures for the years 2000–2014 included the MeSH terms “tension‐free vaginal tape,” “TVT,” “trans‐obturator tape,” “TOT,” “Burch colposuspension” (BC), “stress urinary incontinence,” “economic analysis,” and “cost‐effectiveness analysis.” Important criteria for evaluating articles were selected from panels that set out criteria to evaluate EA [Scales CD, Jr., Christopher SS, American Urological Association 32:121–128, 2013], [Hsieh MH, Maxwell MV, J Urol 178 1867–1874, 2007], [Wu JM, Catherine CM, Conover MM, et al., Obstet Gynecol 123 1201–1206, 2014].

Results

Thirteen articles were identified: TVT compared to BC (6), to other surgical procedures for SUI (1), to TOT (3) and to the mini‐sling (1); open BC compared to laparoscopic BC (1), and analysis of various slings and meshes for various types of incontinence (1). Articles originated from: United States (3), Europe (4), United Kingdom (4), and Canada (2). Eight described cost‐effectiveness analysis (CEA), two cost‐utility analysis, and three cost comparison. Follow‐up time for patients ranged from 6 to 24 months in eight articles, with four having a minimum of 24 months follow‐up. Studies mostly adhered to the criteria, however indirect costs, sensitivity analysis, and efficacy parameters varied. Long‐term synthetic sling‐related complications were not included.

Conclusion

Although CEA for SUI surgery is a burgeoning field, study comparisons remain difficult due to some variability, including health care delivery systems. As women live longer, long‐term data will become critical as complications and reoperations can affect the real cost of SUI corrective procedures. Neurourol. Urodynam. 35:1040–1045, 2016. © 2015 Wiley Periodicals, Inc.
Left‐colon antegrade enema (LACE): Long‐term experience with the Macedo‐Malone approach
Authors: Anselmo Christophe B. , do Amaral Rafael D.R. , Oliveira Diego E.G. , da Cruz Marcela Leal , Liguori Riberto , Garrone Gilmar , Leslie Bruno , Ottoni Sérgio L. , Ortiz Valdemar , Macedo Jr Antonio
Published: September 2015

Aims

We evaluated the long‐term results with a left antegrade continence enema (LACE) approach: “Macedo–Malone (MM) procedure” to define parameters such as clinical durability of the technique and patients' compliance with the method.

Methods

We reviewed the medical records of all patients that underwent the MM procedure in our institution since 2001 and conducted a telephonic interview to investigate the use of the enema and satisfaction with the procedure.

Results

Thirty‐five MM procedures were performed, but eight patients lost to follow‐up were excluded. Fifteen patients (55%) were female. Myelomeningocele was the clinical diagnoses in 25 (93%). Mean age at surgery was 9 years (3–27 years) and mean follow‐up was 75 months (median: 56 months). The indication for LACE was clinically intractable constipation with fecal leakage. Most patients still used the stoma regularly to do the enema (74%). Mean washout time was 27 min (2–90 min). The revision rate due to stenosis was 22.2% (6/27) and all underwent suprafascial revision. We performed one classical MACE by infrafascial approach as a salvage procedure. Overall reoperation rate was 25.8% and fecal continence was 89%. There were no reports of leakage through the stoma. Among patients who still used the stoma, 74% were satisfied with surgery and would strongly recommend the procedure to another patient.

Conclusions

The MM procedure is a straightforward procedure, which can be performed in 15–20 min, avoids additional entero–entero anastomosis, precludes the use of the appendix, and has shown comparable results to either “classical” MACE or other LACE variants. Neurourol. Urodynam. 36:111–115, 2017. © 2015 Wiley Periodicals, Inc.
SRLG failure localization using nested m‐trails and their application to adaptive probing
Authors: Ali Mohammed L. , Ho Pin‐Han , Tapolcai János
Published: September 2015

This article explores a recently introduced novel technique called the nested monitoring trail (m‐trail) method in all‐optical mesh networks for failure localization of any shared risk link group (SRLG) with up to undirected links. The nested m‐trail method decomposes each network topology that is at least ‐connected into virtual cycles and trails, in which sets of m‐trails that traverse through a common monitoring node (MN) can be obtained. The nested m‐trails are used in the monitoring burst (m‐burst) framework, in which the MN can localize any SRLG failure by inspecting the optical bursts traversing through it. An integer linear program (ILP) and a heuristic are proposed for the network decomposition, which are further verified by numerical experiments. We show that the proposed method significantly reduces the required fault localization latency compared with the existing methods. Finally, we demonstrate that nested m‐trails can also be used in adaptive probing to find SRLG faults in all‐optical networks. The nested m‐trail based probing method needs a significantly reduced number of sequential probes. Thus, the method overcomes one of the important hurdles to deploy adaptive probing in all‐optical networks: the large number of sequential probes needed to localize SRLG faults. © 2015 Wiley Periodicals, Inc. NETWORKS, Vol. 66(4), 347–363 2015