bluuebunny/crossref_metadata_2025 huggingface dataset:
Early ethanol exposure and vinpocetine treatment alter learning‐ and memory‐related proteins in the rat hippocampus and prefrontal cortex
Authors: Swart Patricia C. , Currin Christopher B. , Russell Vivienne A. , Dimatelis Jacqueline J.
Published: September 2016

This study investigates the effects of early exposure to ethanol on cognitive function and neural plasticity‐related proteins in the rat brain. Sprague‐Dawley rats were administered 12% ethanol solution (4 g/kg/day i.p.) or saline from P4 to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine whether it could reverse any changes induced by early ethanol exposure. Hence, from P25 to P31, ethanol‐exposed male rats were injected with vinpocetine (20 mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely affect spatial memory in the MWM. A key finding in this study was a significant ethanol‐induced change in the function of the phosphorylated extracellular signal‐related kinase (P‐ERK) signaling pathway in the prefrontal cortex (PFC) and dorsal hippocampus (DH) of rats that did not display overt behavioral deficits. The P‐ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol‐exposed rats compared with controls. Rats that received vinpocetine in addition to ethanol did not display any behavioral changes but did show alterations in neural plasticity‐related proteins. Mitogen‐activated protein kinase phosphatase was increased, whereas brain‐derived neurotrophic factor was decreased, in the PFC of vinpocetine‐treated ethanol‐exposed rats, and phosphorylated‐glycogen synthase kinase β and synaptophysin were increased in the DH of these rats. This study provides insight into the long‐term effects of early ethanol exposure and its interaction with vinpocetine in the rat brain. © 2016 Wiley Periodicals, Inc.
Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury
Authors: Moretti Raffaella , Chhor Vibol , Bettati Donatella , Banino Elena , De Lucia Silvana , Le Charpentier Tifenn , Lebon Sophie , Schwendimann Leslie , Pansiot Julien , Rasika Sowmyalakshmi , Degos Vincent , Titomanlio Luigi , Gressens Pierre , Fleiss Bobbi
Published: September 2016

The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than injuries to the adult brain. Understanding this developmental sensitivity is critical because children under 4 years of age of sustain TBI more frequently than any other age group. One of the first events after TBI is the infiltration and degranulation of mast cells (MCs) in the brain, releasing a range of immunomodulatory substances; inhibition of these cells is neuroprotective in other types of neonatal brain injury. This study investigates for the first time the role of MCs in mediating injury in a P7 mouse model of pediatric contusion‐induced TBI. We show that various neural cell types express histamine receptors and that histamine exacerbates excitotoxic cell death in primary cultured neurons. Cromoglycate, an inhibitor of MC degranulation, altered the inflammatory phenotype of microglia activated by TBI, reversing several changes but accentuating others, when administered before TBI. However, without regard to the time of cromoglycate administration, inhibiting MC degranulation did not affect cell loss, as evaluated by ventricular dilatation or cleaved caspase‐3 labeling, or the density of activated microglia, neurons, or myelin. In double‐heterozygous cKit mutant mice lacking MCs, this overall lack of effect was confirmed. These results suggest that the role of MCs in this model of pediatric TBI is restricted to subtle effects and that they are unlikely to be viable neurotherapeutic targets. © 2016 Wiley Periodicals, Inc.
Preferential conduction block of myelinated axons by nitric oxide
Authors: Shrager Peter , Youngman Margaret
Published: September 2016

Conduction block by nitric oxide (NO) was examined in myelinated and unmyelinated axons from both the central nervous system and peripheral nervous system. In rat vagus nerves, mouse optic nerves at P12–P23, adult and developing mouse sciatic nerves, and mouse spinal cords, myelinated fibers were preferentially blocked reversibly by concentrations of NO similar to those encountered in inflammatory lesions. The possibility that these differences between myelinated and unmyelinated axons are due to the normal developmental substitution of Na+ channel subtype Nav1.6 for Nav1.2 at nodes of Ranvier was tested by repeating experiments on mice null for Nav1.6. Results were unchanged in this mutant. In shiverer optic nerve, which has only scattered regions with nodes of Ranvier, only the fastest component of the compound action potential was reduced. NO was compared with three other methods of blocking conduction: low Na+, high K+, and tetrodotoxin (TTX). In each of these three cases, unmyelinated axons lost conduction simultaneously with myelinated fibers. From changes in conduction velocity in myelinated axons as they were blocked, it was ascertained that NO acted most similarly to TTX. It was concluded that NO likely interacts with axonal Na+ channels through an intermediate that is associated with myelin. © 2016 Wiley Periodicals, Inc.
Sugars and organic acids in plum fruit affected by Plum pox virus
Authors: Usenik Valentina , Marn Mojca Virscek
Published: September 2016

BACKGROUND

Plum pox virus (PPV) causes severe economic losses in stone fruit production, but little is known about its effect on plum fruit composition. In this study, the influence of PPV on sugars and organic acids was evaluated in a susceptible plum (Prunus domestica L.) cultivar.

RESULTS

PPV infection significantly affected the content and composition of sugars and organic acids. The composition of necrotic tissue was modified the most. A short‐time infected tree yielded fruit with similar sugar composition to fruit from a healthy tree, but the decline of organic acids was faster. Prematurely ripened symptomatic fruit had reduced fruit weight and low sugar content.

CONCLUSION

Infected trees of the studied cultivar produce fruit of inferior quality. Fruits are not suitable for processing, especially when most of them exhibit visual symptoms of PPV infection. © 2016 Society of Chemical Industry
LESSONS OF THE SUPERBOSSES
Authors: Finkelstein Sydney
Published: September 2016

Finkelstein has studied people he calls “superbosses” in a number of industries, including hospitals (Tommy Frist), hedge funds (Julian Robertson), newspapers (Gene Roberts), and filmmaking (George Lucas). Finkelstein contends all bosses and managers should share the following attributes: “developing world‐class talent who can adapt and adjust, learn to get better at whatever they do, and in the final analysis, create value for themselves and their organizations.” He found that superbosses were demanding of others, yet also demanding of themselves, and willing to share responsibility while continually imparting wise teaching lessons. Above all, they “help other people accomplish more than they ever thought possible.”
INSPIRING STORYTELLERS TRANSFORM EMPLOYEES INTO CRUSADERS
Authors: Gallo Carmine
Published: September 2016

Gallo cites research that shows how employees believed a “higher purpose” can motivate them to go the extra mile. He found that storytelling helps achieve that purpose, and is crucial to leadership. Particularly powerful are origin stories about organizations and heroic tales of customer service. Gallo relates stories of powerful corporate communicators, such as Howard Schultz, CEO and chairman of Starbucks, and draws on research in neuroscience about the power of stories to inspire people in profound ways. “Customers don't buy a brand or a logo,” Gallo writes, “as much as they buy into a set of values.” And often stories are the embodiment of those values.
STRAGILITY: THE ULTIMATE COMPETITIVE ADVANTAGE
Authors: Auster Ellen R. , Hillenbrand Lisa
Published: September 2016

Auster and Hillenbrand introduce Stragility, described as the “art of strategic, agile, people‐powered change.” They discuss four interrelated skills: “sensing and shifting, embracing our inner politician, inspiring and engaging, and cultivating change fitness.” They draw on such corporate examples as Apple, Macy's, and Whole Foods Market. There is also the counter‐example of Research in Motion—later renamed BlackBerry, Ltd.—and the loss of their business to Apple and its iPhones. Stragility requires hyper‐awareness and the ability and willingness to listen to skeptics and critics. “We need to anticipate disruptive game changers,” the authors write, “and monitor our competitive landscape while also keeping an eye on what's happening on the periphery.”
LEADERSHIP, MARKETING, AND THE NEW MAJORITY
Authors: Bowman Jeffrey L.
Published: September 2016

Once thought of as minority segments of the population—“women, Hispanics, African American, Asian American, and LBGT”—have now shifted to the New Majority, in Bowman's terminology. Yet he contends most marketers and organizations are not aware of or prepared for this fundamental change. He describes the five maturity levels of what he calls “Total Market Enterprise.” The four elements within each level are, in his words: market sizing, organizational design and partnerships, experience and engagements, and measurement. “The goal of every leader,” Bowman writes, “should be to be open and inviting to every segment of the workforce and marketplace—not just those who may have held economic power in the past.”
ARE YOU LIVING TO WORK, OR WORKING TO LIVE?
Authors: Holligan Andy
Published: September 2016

Holligan believes that many of us are unhappy and stressed because work has become an end in itself and not a means to achieving our dreams. He points out that dreams don't necessarily have to be material; they can involve spending more time with family and friends, or turning a hobby into a business. It's also helpful to carve out “Me time” (time for yourself), as well as time for meditation or relaxation and exercise. Write down your dreams so that they are always available to you, and create pictures as well, because concrete expressions and visions make our dreams seem more real and capable of being achieved.
Clinical and neurophysiological features of familial cortical myoclonic tremor with epilepsy
Authors: Cen Zhidong , Huang Chunping , Yin Houmin , Ding Xueping , Xie Fei , Lu Xingjiao , Ouyang Zhiyuan , Lou Yuting , Qiu Xia , Wang Zhongjin , Xiao Jianfeng , Ding Meiping , Luo Wei
Published: September 2016

Objective

Familial cortical myoclonic tremor with epilepsy is a rare epilepsy syndrome. Herein, we report on nine Chinese familial cortical myoclonic tremor with epilepsy pedigrees to delineate its clinical and neurophysiological features.

Methods

Detailed clinical and neurophysiological data were obtained. Somatosensory evoked potential amplitudes and clinical profile were analyzed using multilevel statistical models. Age‐at‐onset anticipation was analyzed using Kaplan‐Meier survival analysis.

Results

Fifty‐five patients were interviewed directly, whose mean age at onset of cortical tremor and generalized tonic‐clonic seizures were 31.0 ± 8.3 and 36.0 ± 7.9 years. Giant somatosensory evoked potential was detected in 87.5% (28 of 32) of patients, and long‐latency cortical reflex was detected in 93.5% (29 of 31). Cortical tremor severity was significantly higher in patients with longer disease duration of cortical tremor (P = 0.0061). Somatosensory evoked potential amplitudes were significant higher in patients with higher level of cortical tremor severity (P = 0.0003) and those using antiepileptic drugs (P = 0.0150). Age‐at‐onset anticipation of cortical tremor with paternal transmission was found with statistical significance (P = 0.022).

Conclusion

We provided the clinical and neurophysiological features of familial cortical myoclonic tremor with epilepsy patients. This study is reported for the presentation of this rare disease in a Chinese population with the largest single report on familial cortical myoclonic tremor with epilepsy worldwide. Age‐at‐onset anticipation of cortical tremor with paternal transmission was statistically significant, which further confirmed a possibility of unstable expanding repeat in the genetic mechanism of familial cortical myoclonic tremor with epilepsy. © 2016 International Parkinson and Movement Disorder Society
Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro
Authors: McDougall Gordon J. , Allwood J. William , Pereira‐Caro Gema , Brown Emma M. , Verrall Susan , Stewart Derek , Latimer Cheryl , McMullan Geoff , Lawther Roger , O'Connor Gloria , Rowland Ian , Crozier Alan , Gill Chris I. R.
Published: September 2016

Scope

Ileostomy studies provide a unique insight into digestion of food, allowing identification of physiologically relevant dietary phytochemicals and their metabolites important to gut health. We previously reported the consistent increase of components in ileal fluids of ileostomates after consumption of raspberries with use of nontargeted LC–MSn techniques and data deconvolution software highlighting two major unknown components (m/z 355 and 679).

Methods and results

In‐depth LC–MSn analyses suggested that the ileal m/z 355 components were p‐coumaroyl glucarates. These compounds have not been identified previously and were confirmed in raspberry extracts after partial purification. The major ileal component with m/z 679 was a glycoside with an aglycone of m/z 517 and was present as two peaks in extracts of whole puree, unseeded puree, and isolated seeds. These components were purified using Sephadex LH20 and C18 SPE units and identified as major, novel raspberry triterpenoid glycosides. This triterpenoid‐enriched fraction (100 nM) protected against H2O2‐induced DNA damage in both colon cancer and normal cell lines and altered expression of cytoprotective genes.

Conclusion

The presence of these novel raspberry triterpenoid components in ileal fluids indicates that they would be colon‐available in vivo, so confirmation of their anticancer bioactivities is of key physiological relevance.
Globalization technique for projected Newton–Krylov methods
Authors: Chen Jinhai , Vuik Cornelis
Published: September 2016

Large‐scale systems of nonlinear equations appear in many applications. In various applications, the solution of the nonlinear equations should also be in a certain interval. A typical application is a discretized system of reaction diffusion equations. It is well known that chemical species should be positive otherwise the solution is not physical and in general blow up occurs. Recently, a projected Newton method has been developed, which can be used to solve this type of problems. A drawback is that the projected Newton method is not globally convergent. This motivates us to develop a new feasible projected Newton–Krylov algorithm for solving a constrained system of nonlinear equations. Combined with a projected gradient direction, our feasible projected Newton–Krylov algorithm circumvents the non‐descent drawback of search directions which appear in the classical projected Newton methods. Global and local superlinear convergence of our approach is established under some standard assumptions. Numerical experiments are used to illustrate that the new projected Newton method is globally convergent and is a significate complementarity for Newton–Krylov algorithms known in the literature. © 2016 The Authors. International Journal for Numerical Methods in Engineering Published by John Wiley & Sons Ltd.
Synthesis and characterization of new polydiolcitrates with tunable properties
Authors: Nuvoli Daniele , Alzari Valeria , Nuvoli Luca , Rassu Mariella , Sanna Davide , Sanna Vanna , Mariani Alberto
Published: September 2016

Polydiolcitrates are an emerging class of biocompatible polyesters with a great potential in the field of biomedicine and packaging for food and drug materials. In this work, a new type of (co‐)polydiolcitrates made of citric acid (CA) and ethylene glycol (EG) and/or poly(ethylene glycol) (PEG) is investigated. By varying both the EG/PEG and the CA/diol molar ratios, materials exhibiting very different swelling behavior, mechanical and thermal properties are obtained. In particular, the substitution of EG segments with longer and flexible PEG ones results in an increase in crosslinking density, with remarkable effects on swelling capacity, glass transition temperature, and Young modulus. Moreover, polyesters with CA/diol molar ratio equal to 1:1 exhibit shape memory properties, with full capacity of keeping the temporary shape and high capacity of recovering the original shape. This work demonstrates that the appropriate choice of polyester composition allows modulating the sample properties, that permits to these materials to cover a wide range of possible applications. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2016,54, 3713–3720
Federal Investments in Evidence‐Based Early Childhood Home Visiting: A Multiple Streams Analysis
Authors: Barton Jared Lee
Published: September 2016

Child poverty, child maltreatment, and child health and development are major public policy issues. By the end of the Great Recession in 2009, as many as one in four children under the age of five were living in poverty and six million children were subject to child maltreatment reports in America. For decades, evidence‐based home visiting (EBHV) programs have provided effective early interventions for preventing child maltreatment and promoting child and family outcomes to pregnant women and families with children age birth to five years old. Despite this, no widespread federal policies or funding supported home visiting before 2010. Through the Patient Protection and Affordable Care Act (ACA), the federal government invested $1.5 billion in home visiting with the Maternal, Infant, and Early Childhood Home Visiting (MIECHV) initiative. While many articles examine the effectiveness of home visiting and call attention to the unprecedented features of MIECHV, this article applies the multiple streams framework to illuminate the unique social and political contexts culminating in the inclusion of MIECHV in ACA. The findings in this article are significant for policy analysts, advocates, and program developers and for establishing policies requiring evidence‐based practices.
Shining Light on Dark Politics: An Essay and Review
Authors: Skidmore Max J.
Published: September 2016

Max J. Skidmore considers the state of anti‐poverty legislation and programs in the United States, as well as the general condition of American politics today. In the course of his essay, he reviews a number of relevant studies and describes the dark forces that are explicitly attacking programs that improve the lives of Americans. He discusses the imposition of “dark money” throughout the American political system that has replaced truth with lies and warped perceptions, and distorted the “will of the people.” Setting aside gentility and the natural tendency to want to avoid giving offense, he directs blame, and concludes that these “dark forces” have brought the country to a perilous position by having distorted and clouded “centrist” opinions. He demonstrates, nevertheless, that counterforces have emerged, and are becoming stronger. He recommends a course of action: citizens must become sensitive to “false equivalency” and other arguments that obscure reality. Moreover, however as counterintuitive as it appears, the dynamics of American politics demand a frankly partisan approach with straight‐ticket voting.
Poverty in the United States: A Review of Relevant Programs
Authors: Varghese Shabu Abraham
Published: September 2016

Poverty is a major social problem in the United States: in 2014, the U.S. Census Bureau reported 46.7 million people living in poverty and an estimated 14.8 percent poverty rate. The poverty rate has been steadily increasing in the United States, with a 2 percent increase in 2012 over 2007. Federal and state governments have initiated many anti‐poverty programs, starting with the New Deal Program in the 1930s. With the advent of a new governance approach in the 1990s, many hierarchical bureaucratic government agencies were replaced with public, private, network, and collaborative approaches to solve this complex national problem. Tax expenditures, vouchers, and grants are the three major governance tools used by the U.S. federal and state governments to fight poverty. This article addresses three important programs—the Earned Income Tax Credit (EITC), the Supplemental Nutrition Assistance Program (SNAP), and Temporary Assistance for Needy Families (TANF)—used in fighting poverty in the United States and discusses the problem of poverty, the effectiveness of these governance tools, suggestions for future research, and policy implications
A simple method for estimating the effective detection distance of camera traps
Authors: Hofmeester Tim R. , Rowcliffe J. Marcus , Jansen Patrick A.
Published: September 2016

Estimates of animal abundance are essential for understanding animal ecology. Camera traps can be used to estimate the abundance of terrestrial mammals, including elusive species, provided that the sensitivity of the sensor, estimated as the effective detection distance (EDD), is quantified. Here, we show how the EDD can be inferred directly from camera trap images by placing markers at known distances along the midline of the camera field of view, and then fitting distance‐sampling functions to the frequency of animal passage between markers. EDD estimates derived from simulated passages using binned detection distances approximated those obtained from continuous detection distance measurements if at least five intervals were used over the maximum detection distance. A field test of the method in two forest types with contrasting vegetation density, with five markers at 2.5 m intervals, produced credible EDD estimates for 13 forest‐dwelling mammals. EDD estimates were positively correlated with species body mass, and were shorter for the denser vegetation, as expected. Our findings suggest that this simple method can produce reliable estimates of EDD. These estimates can be used to correct photographic capture rates for difference in sampling effort resulting from differences in sensor sensitivity between species and habitats. Simplifying the estimation of EDD will result in less biased indices of relative abundance, and will also facilitate the use of camera trap data for estimating animal density.
Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A Horse in the Race?
Authors: Wolf Don P. , Morey Robert , Kang Eunju , Ma Hong , Hayama Tomonari , Laurent Louise C. , Mitalipov Shoukhrat
Published: September 2016

Embryonic stem cells (ESC) hold promise for the treatment of human medical conditions but are allogeneic. Here, we consider the differences between autologous pluripotent stem cells produced by nuclear transfer (NT-ESCs) and transcription factor-mediated, induced pluripotent stem cells (iPSCs) that impact the desirability of each of these cell types for clinical use. The derivation of NT-ESCs is more cumbersome and requires donor oocytes; however, the use of oocyte cytoplasm as the source of reprogramming factors is linked to a key advantage of NT-ESCs—the ability to replace mutant mitochondrial DNA in a patient cell (due to either age or inherited disease) with healthy donor mitochondria from an oocyte. Moreover, in epigenomic and transcriptomic comparisons between isogenic iPSCs and NT-ESCs, the latter produced cells that more closely resemble bona fide ESCs derived from fertilized embryos. Thus, although NT-ESCs are more difficult to generate than iPSCs, the ability of somatic cell nuclear transfer to replace aged or diseased mitochondria and the closer epigenomic and transcriptomic similarity between NT-ESCs and bona fide ESCs may make NT-ESCs superior for future applications in regenerative medicine.
Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells
Authors: Aguado Tania , Gutiérrez Francisco J. , Aix Esther , Schneider Ralph P. , Giovinazzo Giovanna , Blasco María A. , Flores Ignacio
Published: September 2016

Induced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo to all cardiovascular lineages and are therefore a promising cell source for cardiac regenerative therapy. However, iPSC lines do not all differentiate into cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase-competent iPSCs with relatively long telomeres and high expression of the shelterin-complex protein TRF1 (iPSChighT) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSClowT). Ascorbic acid, an enhancer of cardiomyocyte differentiation, further increases the cardiomyocyte yield from iPSChighT but does not rescue the cardiomyogenic potential of iPSClowT. Interestingly, although iPSCslowT differentiate very poorly to the mesoderm and endoderm lineages, they differentiate very efficiently to the ectoderm lineage, indicating that cell fate can be determined by in vitro selection of iPSCs with different telomere content. Our findings highlight the importance of selecting iPSCs with ample telomere reserves in order to generate high numbers of CMs in a fast, reliable, and efficient way.
Effect of Addition of Purified Diglycerol Linoleic Acid Esters on the Crystallization Behavior of Diacylglycerol Oils
Authors: Wan Fenlong , Teng Yinglai , Zou Long , Yang Xue , Chen Qiong , Li Aijun , Wang Yong
Published: September 2016

Liquid oils containing high‐melting diacylglycerols (DAGs) are more likely to cause precipitation than triacylglycerol‐based oils during long‐term storage, which is not desired for consumer products. Therefore, we attempted to retard the crystallization of high‐melting DAGs by adding emulsifiers, diglycerol esters of fatty acids (DGEs), which were synthesized by esterification of diglycerol and linoleic acid using Novozym 435. The reaction product was isolated by silica gel column chromatography to obtain pure mono‐, di‐, and triesters of diglycerol, and the composition was analyzed by HPLC and ESI‐MS. Further structural analysis of the purified products was performed by 1H‐ and 13C‐NMR. The retardation effect of DGEs with a different esterification degree on the crystallization of DAGs was investigated using solid fat content, differential scanning calorimetry, polarized light microscopy, and X‐ray diffraction. The results reveal that addition of 0.5 % (w/w) DGEs could effectively retard the crystallization of high‐melting DAGs by inhibiting the nucleation process and delaying the crystal growth, but their addition did not alter the crystal forms of DAGs. Moreover, the retardation effect was enhanced as the esterification degree of DGE decreased.
Comparing the mechanical strength of hip spica cast between a conventional and a new method of application
Authors: Wan Kwong-Lee , Shanmugam Rukmanikanthan , Lee Kun-Yun , Saw Aik
Published: September 2016

Purpose

The current technique of hip spica application is mostly based on a publication by Kumar (J Pediatr Orthop 1(1):97–99, 1981 ). We modified the technique of hip spica application in order to reduce the rate of breakage across the hip joint and designed this study to compare the strength between hip spica applied according to Kumar's technique and the new technique.

Methods

We created 12 hip spica casts with 24 hips according to Kumar's technique, and another 12 casts according to a new technique. The two types of spica were tested with a mechanical testing machine (Instron 3365 series) by using compression loading to failure in flexion, extension, abduction and adduction. Data were analysed in SPSS version 20.0. Comparison of means was done with an independent T test for normally distributed data and the Mann–Whitney test for skewed data.

Results

The new technique involved the creation of three slabs, instead of 14 slabs as described by Kumar. The loads to failure for hip spica cast applied according to the new technique were higher than those applied according to Kumar's technique, and the differences were statistically significant. The stiffness was also higher in spica casts applied with the new technique; the difference was not statistically significant under extension force.

Conclusion

Hip spica applied with the new technique was stronger than that applied according to Kumar's technique based on load to failure testing. The new technique of application would potentially reduce the risk of cast breakage during the management of developmental dysplasia of the hip (DDH) and femur fracture in children.
How Well Are We Respecting Patient Privacy in Medical Imaging? Lessons Learnt from a Departmental Audit
Authors: Dilauro Marc , Thornhill Rebecca , Fasih Najla
Published: September 2016

Rationale and Objectives

Preservation of patient privacy and dignity are basic requirements for all patients visiting a hospital. The purpose of this study was to perform an audit of patients' satisfaction with privacy whilst in the Department of Medical Imaging (MI) at the Civic Campus of the Ottawa Hospital.

Materials and Methods

Outpatients who underwent magnetic resonance imaging (MRI), computed tomography (CT), ultrasonography (US), and plain film (XR) examinations were provided with a survey on patient privacy. The survey asked participants to rank (on a 6-point scale ranging from 6 = excellent to 1 = no privacy) whether their privacy was respected in 5 key locations within the Department of MI. The survey was conducted over a consecutive 5-day period.

Results

A total of 502 surveys were completed. The survey response rate for each imaging modality was: 55% MRI, 42% CT, 45% US, and 47% XR. For each imaging modality, the total percentage of privacy scores greater than or equal to 5 were: 98% MRI, 96% CT, 94% US, and 92% XR. Privacy ratings for the MRI reception and waiting room areas were significantly higher in comparison to the other imaging modalities ( P = .0025 and P = .0227, respectively).

Conclusion

Overall, patient privacy was well respected within the Department of MI.
Acute promyelocytic leukemia with increased bone marrow reticulin fibrosis
Authors: Dalle Iman Abou , Nassif Samer , Bazarbachi Ali
Published: September 2016

Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In acute leukemia, one-third of patients have some degree of marrow reticulin fibrosis at presentation, which is thought to be related to cytokine release from blasts. Marrow fibrosis is particularly common in acute megakaryoblastic leukemia, while this change is rarely seen in acute promyelocytic leukemia. Six case reports of acute promyelocytic leukemia with marrow reticulin fibrosis have been described so far in the literature. Herein, we present three cases of classical acute promyelocytic leukemia with increased marrow reticulin fibrosis encountered in our institution, summarizing their clinicopathologic features, treatment, and outcome to date. Awareness of the features of acute promyelocytic leukemia with marrow reti-culin fibrosis is important as it may guide treatment options.
Polycythemia vera masked due to severe iron deficiency anemia
Authors: Kambali Shweta , Taj Asma
Published: September 2016

Polycythemia vera is one of the chronic myeloproliferative diseases and very few patients present with its actual clinical manifestations. The most common findings are increased red cell mass and an increased leukocyte count with decreased erythropoietin. We present a case where there was a delay in the diagnosis of polycythemia because of menorrhagia in the past. On admission, the patient presented with elevated red and white blood cell counts, erythropoietin was low, and polycythemia was then suspected. A bcr-abl test was performed to rule out chronic myelogenous leukemia. JAK2 mutation was positive, and the patient was diagnosed with polycythemia vera.
Short bowel syndrome: treatment options
Authors: Eça Rosário , Barbosa Elisabete
Published: September 2016

Introduction Short bowel syndrome (SBS) refers to the malabsorptive state that occurs following extensive intestinal resection and is associated with several complications.

Methods The research for this review was conducted in the Pubmed database. Relevant scientific articles dated between 1991 and 2015 and written in Portuguese, Spanish or English were selected.

Results Several therapies, including nutritional support, pharmacological options and surgical procedures have been used in these patients.

Conclusions Over the last decades new surgical and pharmacological approaches emerged, increasing survival and quality of life (QoL) in patients with SBS. All SBS patients ought to have an individualized and multidisciplinary care that promotes intestinal rehabilitation.
Lifestyle Factors and Premature Ejaculation: Are Physical Exercise, Alcohol Consumption, and Body Mass Index Associated with Premature Ejaculation and Comorbid Erectile Problems?
Authors: Ventus Daniel , Jern Patrick
Published: September 2016

Introduction

Premature ejaculation (PE) is a common sexual problem in men, but its etiology remains uncertain. Lifestyle factors have long been hypothesized to be associated with sexual problems in general and have been proposed as risk factors for PE.

Aim

To explore associations among physical exercise, alcohol use, body mass index, PE, and erectile dysfunction.

Methods

A population-based sample of Finnish men and a sample of Finnish men diagnosed with PE were surveyed for statistical comparisons. Participants using selective serotonin reuptake inhibitors or other medications known to affect symptoms of PE were excluded from analyses.

Main Outcome Measures

Self-report questionnaires: Multiple Indicators of Premature Ejaculation, International Index of Erectile Function–5, Alcohol Use Disorders Identification Test, and Godin Leisure-Time Exercise Questionnaire.

Results

The clinical sample reported lower levels of physical exercise (mean = 27.53, SD = 21.01, n = 69) than the population-based sample (mean = 34.68, SD = 22.82, n = 863, t930 = 2.52, P = .012), and the effect size was large (d = 0.85). There was a small negative correlation between levels of physical exercise and symptoms of PE (r = −0.09, P < .01, n = 863) in the population-based sample. The association between physical exercise and PE remained significant after controlling for effects of age, erectile dysfunction, alcohol use, and body mass index.

Conclusion

If future studies show that the direction of causality of this association is such that physical activity alleviates PE symptoms, then including physical activity in PE treatment interventions could be a promising addition to treatment regimes.
Scientists Get First Glimpse of Solar Wind as It Forms
Authors: Wendel JoAnna
Published: September 2016

Using computer-processed images from Sun-watching satellites, scientists observed solar wind emerging from the Sun's corona.
John A. Knauss (1925–2015)
Authors: Leinen Margaret , Corliss Bruce , Duce Robert
Published: September 2016

Knauss, an oceanographer who fiercely advocated for national and global marine initiatives, helped to develop many iconic programs and institutions that are key parts of oceanography today.
Atmospheric Chemists Should Tackle Risks to Society, Report Says
Authors: Showstack Randy
Published: September 2016

Protecting public health and the health of the climate and ecosystems warrants more focus from this scientific field, according to the report.
Crystal structure and enantioselectivity of terpene cyclization in SAM-dependent methyltransferase TleD
Authors: Yu Feng , Li Minjun , Xu Chunyan , Sun Bo , Zhou Huan , Wang Zhijun , Xu Qin , Xie Muyun , Zuo Gang , Huang Pei , Guo Haojie , Wang Qisheng , He Jianhua
Published: September 2016

TleD is a SAM (S-adenosyl-l-methionine)-dependent methyltransferase and acts as one of the key enzymes in the teleocidin B biosynthesis pathway. Besides methyl transferring, TleD also rearranges the geranyl and indole moieties of the precursor to form a six-membered ring. Moreover, it does not show homologies with any known terpenoid cyclases. In order to elucidate how such a remarkable reaction could be achieved, we determined the complex crystal structures of TleD and the cofactor analogue S-adenosyl-l-homocysteine with or without the substrate teleocidin A1. A domain-swapped pattern via an additional N-terminal α-helix is observed in TleD hexamers. Structural comparison and alignment shows that this additional N-terminal α-helix is the common feature of SAM methyltransferase-like cyclases TleD and SpnF. The residue Tyr21 anchors the additional N-terminal α-helix to a ‘core SAM-MT fold' and is a key residue for catalytic activity. Molecular dynamics simulation results suggest that the dihedral angle C23–C24–C25–C26 of teleocidin A1 is preferred to 60–90° in the TleD and substrate complex structure, which tend to adopt a Re-face stereocenter at C25 position after reaction and is according to in vitro enzyme reaction experiments. Our results also demonstrate that methyl transfer can be a new chemical strategy for carbocation formation in the terpene cyclization, which is the key initial step.
Bacillus thuringiensis Cyt2Aa2 toxin disrupts cell membranes by forming large protein aggregates
Authors: Tharad Sudarat , Toca-Herrera José L. , Promdonkoy Boonhiang , Krittanai Chartchai
Published: September 2016

Bacillus thuringiensis (Bt) Cyt2Aa2 showed toxicity against Dipteran insect larvae and in vitro lysis activity on several cells. It has potential applications in the biological control of insect larvae. Although pore-forming and/or detergent-like mechanisms were proposed, the mechanism underlying cytolytic activity remains unclear. Analysis of the haemolytic activity of Cyt2Aa2 with osmotic stabilizers revealed partial toxin inhibition, suggesting a distinctive mechanism from the putative pore formation model. Membrane permeability was studied using fluorescent dye entrapped in large unilamellar vesicles (LUVs) at various protein/lipid molar ratios. Binding of Cyt2Aa2 monomer to the lipid membrane did not disturb membrane integrity until the critical protein/lipid molar ratio was reached, when Cyt2Aa2 complexes and cytolytic activity were detected. The complexes are large aggregates that appeared as a ladder when separated by agarose gel electrophoresis. Interaction of Cyt2Aa2 with Aedes albopictus cells was investigated by confocal microscopy and total internal reflection fluorescent microscopy (TIRF). The results showed that Cyt2Aa2 binds on the cell membrane at an early stage without cell membrane disruption. Protein aggregation on the cell membrane was detected later which coincided with cell swelling. Cyt2Aa2 aggregations on supported lipid bilayers (SLBs) were visualized by AFM. The AFM topographic images revealed Cyt2Aa2 aggregates on the lipid bilayer at low protein concentration and subsequently disrupts the lipid bilayer by forming a lesion as the protein concentration increased. These results supported the mechanism whereby Cyt2Aa2 binds and aggregates on the lipid membrane leading to the formation of non-specific hole and disruption of the cell membrane.
The influence of glycation on a high pressure denaturation of ubiquitin
Authors: Kijewska Monika , Radziszewska Karolina , Cal Marta , Waliczek Mateusz , Stefanowicz Piotr , Szewczuk Zbigniew
Published: September 2016

The combination of deuterium–hydrogen exchange (DHX) and mass spectrometry (MS) can be used for studying a high pressure denaturation (HPD) of proteins. Herein we present the results of investigations of the influence of glycation on the HPD of ubiquitin. Application of various values of pressure causes different degrees of protein unfolding, resulting in molecules with a different number of protons available for exchange with deuterons. The dependence of this number on pressure gives information on the denaturation state of a protein. On the basis of the obtained results we can conclude that increasing number of fructosamine moieties in ubiquitin decreases the pressure required for its denaturation. It suggests that glycation moderately decreases the protein stability. The present study is the first example of application of hydrogen–deuterium exchange as a method of investigating the influence of posttranslational modification of protein on the HPD.
Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis
Authors: Callera Glaucia E. , Antunes Tayze T. , Correa Jose W. , Moorman Danielle , Gutsol Alexey , He Ying , Cat Aurelie Nguyen Dinh , Briones Ana M. , Montezano Augusto C. , Burns Kevin D. , Touyz Rhian M.
Published: September 2016

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes.
Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway
Authors: Yuan Yujia , Shi Meimei , Li Lan , Liu Jingping , Chen Bo , Chen Younan , An Xingxing , Liu Shuyun , Luo Ruixi , Long Dan , Zhang Wengeng , Newsholme Philip , Cheng Jingqiu , Lu Yanrong
Published: September 2016

Vasculopathy is a major complication of diabetes. Impaired mitochondrial bioenergetics and biogenesis due to oxidative stress are a critical causal factor for diabetic endothelial dysfunction. Sirt1, an NAD+-dependent enzyme, is known to play an important protective role through deacetylation of many substrates involved in oxidative phosphorylation and reactive oxygen species generation. Mesenchymal stem cell-conditioned medium (MSC-CM) has emerged as a promising cell-free therapy due to the trophic actions of mesenchymal stem cell (MSC)-secreted molecules. In the present study, we investigated the therapeutic potential of MSC-CMs in diabetic endothelial dysfunction, focusing on the Sirt1 signalling pathway and the relevance to mitochondrial function. We found that high glucose-stimulated MSC-CM attenuated several glucotoxicity-induced processes, oxidative stress and apoptosis of endothelial cells of the human umbilical vein. MSC-CM perfusion in diabetic rats ameliorated compromised aortic vasodilatation and alleviated oxidative stress in aortas. We further demonstrated that these effects were dependent on improved mitochondrial function and up-regulation of Sirt1 expression. MSC-CMs activated the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), leading to direct interaction between Akt and Sirt1, and subsequently enhanced Sirt1 expression. In addition, both MSC-CM and Sirt1 activation could increase the expression of peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), as well as increase the mRNA expression of its downstream, mitochondrial, biogenesis-related genes. This indirect regulation was mediated by activation of AMP-activated protein kinase (AMPK). Overall our findings indicated that MSC-CM had protective effects on endothelial cells, with respect to glucotoxicity, by ameliorating mitochondrial dysfunction via the PI3K/Akt/Sirt1 pathway, and Sirt1 potentiated mitochondrial biogenesis, through the Sirt1/AMPK/PGC-1α pathway.
Molecular mechanisms for vascular complications of targeted cancer therapies
Authors: Gopal Srila , Miller Kenneth B. , Jaffe Iris Z.
Published: September 2016

Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future.
N-glycans of growth factor receptors: their role in receptor function and disease implications
Authors: Takahashi Motoko , Hasegawa Yoshihiro , Gao Congxiao , Kuroki Yoshio , Taniguchi Naoyuki
Published: September 2016

Numerous signal-transduction-related molecules are secreted proteins or membrane proteins, and the mechanism by which these molecules are regulated by glycan chains is a very important issue for developing an understanding of the cellular events that transpire. This review covers the functional regulation of epidermal growth factor receptor (EGFR), ErbB3 and the transforming growth factor β (TGF-β) receptor by N-glycans. This review shows that the N-glycans play important roles in regulating protein conformation and interactions with carbohydrate recognition molecules. These results point to the possibility of a novel strategy for controlling cell signalling and developing novel glycan-based therapeutics.