bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition
Authors: Lake Evelyn M.R. , Mester James , Thomason Lynsie AM , Adams Conner , Bazzigaluppi Paolo , Koletar Margaret , Janik Rafal , Carlen Peter , McLaurin JoAnne , Stanisz Greg J , Stefanovic Bojana
Published: November 2016

Purpose

Stroke is the leading cause of adult disability worldwide. The absence of more effective interventions in the chronic stage—that most patients stand to benefit from—reflects uncertainty surrounding mechanisms that govern recovery. The present work investigated the effects of a novel treatment (selective cyclooxygenase‐1, COX‐1, inhibition) in a model of focal ischemia.

Materials and Methods

FR122047 (COX‐1 inhibitor) was given beginning 7 days following stroke (cortical microinjection of endothelin‐1) in 23 adult male rats. Longitudinal continuous‐arterial‐spin‐labeling was performed prior to treatment (7 days), and repeated following treatment (21 days) on a 7T magnetic resonance imaging (MRI) system to estimate resting perfusion and reactivity to hypercapnia. These in vivo measurements were buttressed by immunohistochemistry.

Results

Stroke caused an increase in perilesional resting perfusion (peri‐/contralesional perfusion ratio of 170 ± 10%) and perfusion responses to hypercapnia (180 ± 10%) at 7 days. At 21 days, placebo‐administered rats showed normalized perilesional perfusion (100 ± 20%) but persistent hyperreactivity (190 ± 20%). Treated animals exhibited sustained perilesional hyperperfusion (180 ± 10%). Further, reactivity lateralization did not persist following treatment (peri‐ vs. contralesional reactivity: P = 0.002 at 7 vs. P = 0.2 at 21 days). Hemodynamic changes were accompanied by neuronal loss, increased endothelial density, and widespread microglial and astrocytic activation. Moreover, relative to controls, treated rats showed increased perilesional neuronal survival (22 ± 1% vs. 14.9 ± 0.8%, P = 0.02) and decreased microglia/macrophage recruitment (17 ± 1% vs. 20 ± 1%, P = 0.05). Finally, perilesional perfusion was correlated with neuronal survival (slope = 0.14 ± 0.05; R2 = 0.7, P = 0.03).

Conclusion

These findings shed light on the role of COX‐1 in chronic ischemic injury and suggest that delayed selective COX‐1 inhibition exerts multiple beneficial effects on the neurogliovascular unit.

Level of Evidence: 1

Technical Efficacy: Stage 4

J. MAGN. RESON. IMAGING 2017;46:505–517
Molecular surveillance of dengue in Minas Gerais provides insights on dengue virus 1 and 4 circulation in Brazil
Authors: Dutra Karina Rocha , Drumond Betânia Paiva , de Rezende Izabela Maurício , Nogueira Maurício Lacerda , de Oliveira Lopes Débora , Calzavara Silva Carlos Eduardo , Siqueira Ferreira Jaqueline Maria , dos Santos Luciana Lara
Published: November 2016

Dengue, caused by any of the four types of Dengue virus (DENV) is
the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV‐1 lineages, belonging to genotype V were introduced and co‐circulated in Divinópolis. When compared to each other, those lineages presented high genetic diversity and showed unique amino acids substitutions in the envelope protein, including in domains I, II, and III. DENV‐4 strains from Divinópolis clustered within genotype IIb and the most recent common ancestor was probably introduced into the city three years before the 2013 epidemic. Here we demonstrated for the first time the circulation of DENV‐4 and the co‐circulation of two DENV‐1 lineages in Midwest region of Minas Gerais, Brazil. Moreover our analysis indicated the introduction of five DENV‐1 lineages, genotype V into Brazil, in different times. J. Med. Virol. 89:966–973, 2017. © 2016 Wiley Periodicals, Inc.
Clinical utility of bronchoalveolar lavage cytomegalovirus viral loads in the diagnosis of cytomegalovirus pneumonitis in infants
Authors: Govender Kerusha , Jeena Prakash , Parboosing Raveen
Published: November 2016

Cytomegalovirus (CMV) pneumonitis is a significant cause of morbidity and mortality of children in Africa. The current practice for diagnosing CMV pneumonitis in this setting is based on interpretation of clinical, laboratory, and radiological findings. There is a need for a sensitive and specific laboratory test to objectively distinguish between patients with CMV pneumonitis and those with CMV infection, and non‐CMV pneumonia. In this study, we compared plasma and non‐bronchoscopic bronchoalveolar lavage (NBBAL) CMV viral loads in patients with CMV pneumonitis and those with CMV infection and non‐CMV pneumonia. Receiver operator characteristic curve analysis was used to establish a threshold and assess utility of viral loads in the diagnosis of CMV pneumonitis. We assessed the urea dilution method, and expression of viral loads relative to the total amount of extracted nucleic acids in correcting for NBBAL dilution. CMV quantification in NBBAL specimens was more predictive of CMV pneumonitis than blood CMV quantification. The threshold of 4.03 log IU/ml in NBBAL specimens has good predictive value and can be used to guide management of infants with suspected CMV pneumonitis. Adjusting for dilution of NBBAL specimens by using the urea dilution method or by expressing the viral load relative to the total nucleic acids extracted did not provide additional analytical benefits. J. Med. Virol. 89:1080–1087, 2017. © 2016 Wiley Periodicals, Inc.
A novel iterative algorithm for approximating equivalent circuits of numerical transfer functions
Authors: Zadehgol Ata , Avula Venkatesh
Published: November 2016

Recently, we presented a novel method for pole residue equivalent system solver (PRESS). In this work, we provide the exact solution of local fit types 1, 2, and 3. We also modify the original algorithm to conduct parallel search for optimal solution across all frequencies, instead of targeting only the peak error. We further demonstrate PRESS through application to several numerical examples that are used to discuss convergence rate of solution. Finally, we highlight several topics for further research that could significantly enhance PRESS.
Evolutionary framework for identifying sex‐ and species‐specific vulnerabilities in brain development and functions
Authors: Geary David C.
Published: November 2016

Sexual selection describes the reproductive dynamics that drive the evolution of many sex differences but is rarely used to guide the study of brain development or function. This Mini‐Review describes how these dynamics can result in trait elaboration in one sex or the other and why these traits have a heightened sensitivity to stressors. The framework provides a conceptual model that will help to organize what we know about sex differences in brain and cognition, a means to focus the search for additional sex differences, and a means to predict brain systems that are particularly vulnerable to disruption by exposure to stressors. This Mini‐Review briefly illustrates these points using sex differences in birdsong and spatial navigation to highlight the benefits and the nuances of using evolutionary theory to help frame neuroscience studies of sex differences. © 2016 Wiley Periodicals, Inc.
Understanding the broad influence of sex hormones and sex differences in the brain
Authors: McEwen Bruce S. , Milner Teresa A.
Published: November 2016

Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up‐ or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender‐related behaviors and brain functions. © 2016 Wiley Periodicals, Inc.
Stress, sex, and motivated behaviors
Authors: Laman‐Maharg Abigail , Trainor Brian C.
Published: November 2016

Stress is a major risk factor for development of psychiatric disorders such as depression and development of substance use disorder. Although there are important sex differences in the prevalence of these disorders, most preclinical models used to study stress‐induced disorders have used males only. Social defeat stress is a commonly used method to induce stress in an ethologically relevant way but has only recently begun to be used in female rodents. Using these new female models, recent studies have examined how social defeat stress affects males and females differently at the behavioral, circuit, and molecular levels. This Mini‐Review discusses sex differences in the effects of social defeat stress on social behavior and drug‐seeking behavior as well as its impact on the mesolimbic dopamine system and the highly connected region of the bed nucleus of the stria terminalis. © 2016 Wiley Periodicals, Inc.
Do cortical plasticity mechanisms differ between males and females?
Authors: Dachtler James , Fox Kevin
Published: November 2016

The difference between male and female behavior and male and female susceptibility to a number of neuropsychiatric conditions is not controversial. From a biological perspective, one might expect to see at least some of these differences underpinned by identifiable physical differences in the brain. This Mini‐Review focuses on evidence that plasticity mechanisms differ between males and females and ask at what scale of organization the differences might exist, at the systems level, the circuits level, or the synaptic level. Emerging evidence suggests that plasticity differences may extend to the scale of synaptic mechanisms. In particular, the CaMKK, NOS1 and estrogen receptor pathways show sexual dimorphisms with implications for plasticity in the hippocampus and cerebral cortex. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Sex differences in the anticonvulsant activity of neurosteroids
Authors: Samba Reddy Doodipala
Published: November 2016

Epilepsy is one of the leading causes of chronic neurological morbidity worldwide. Acquired epilepsy may result from a number of conditions, such as brain injury, anoxia, tumors, stroke, neurotoxicity, and prolonged seizures. Sex differences have been observed in many seizure types; however, some sex‐specific seizure disorders are much more prevalent in women. Despite some inconsistencies, substantial data indicates that sensitivity to seizure stimuli differs between the sexes. Men generally exhibit greater seizure susceptibility than women, whereas many women with epilepsy experience a cyclical occurrence of seizures that tends to center around the menstrual period, which has been termedcatamenial epilepsy. Some epilepsy syndromes show gender differences with female predominance or male predominance. Steroid hormones, endogenous neurosteroids, and sexually dimorphic neural networks appear to play a key role in sex differences in seizure susceptibility. Neurosteroids, such as allopregnanolone, reflect sex differences in their anticonvulsant activity. This Review provides a brief overview of the evidence for sex differences in epilepsy and how sex differences influence the use of neurosteroids in epilepsy and epileptogenesis. © 2016 Wiley Periodicals, Inc.
Sex differences in depression during pregnancy and the postpartum period
Authors: Sundström Poromaa Inger , Comasco Erika , Georgakis Marios K. , Skalkidou Alkistis
Published: November 2016

Women have a lifetime risk of major depression double that of men but only during their reproductive years. This sex difference has been attributed partially to activational effects of female sex steroids and also to the burdens of pregnancy, childbirth, and parenting. Men, in contrast, have a reproductive period difficult to delineate, and research on the mental health of men has rarely considered the effects of fatherhood. However, the couple goes through a number of potentially stressing events during the reproductive period, and both mothers and fathers are at risk of developing peripartum depression. This Review discusses the literature on maternal and paternal depression and the endocrine changes that may predispose a person to depression at this stage of life, with specific focus on the hypothalamus–pituitary axis, oxytocin, and testosterone levels in men. Important findings on sex differences in the neural correlates of maternal and paternal behavior have emerged, highlighting the relevance of the emotional brain in mothers and the sociocognitive brain in fathers and pointing toward the presence of a common parents' brain. Additionally, sex differences in neurogenesis and brain plasticity are described in relation to peripartum depression. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Sex differences in brain‐derived neurotrophic factor signaling and functions
Authors: Chan Chi Bun , Ye Keqiang
Published: November 2016

Brain‐derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies have indicated that some functions or action mechanisms of BDNF vary in a sex‐dependent manner. In particular, BDNF content in some brain parts and the tendency to develop BDNF deficiency‐related diseases such as depression are greater in female animals. With the support of relevant studies, it has been suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross‐talk between BDNF and sex steroids has been detected for decades, and some sex steroids, such as estrogen, have a positive regulatory effect on BDNF expression and signaling. Thus, the sex of animal models that are used in studying the functions of BDNF is critical. This Mini‐Review summarizes our current findings on the differences in expression, signaling, and functions of BDNF between sexes. We also discuss the potential mechanisms for mediating these differential responses, with a specific emphasis on sex steroids. By presenting and discussing these findings, we seek to encourage researchers to take sex influences into consideration when designing experiments, interpreting results, and drawing conclusions. © 2016 Wiley Periodicals, Inc.
Sex differences in hippocampal function
Authors: Koss Wendy A. , Frick Karyn M.
Published: November 2016

Sex differences in the function of the hippocampus have been observed in numerous mammalian species. However, the magnitude, extent, and specificity of these differences are unclear because they can depend on factors including age, methodology, and environment. This Review will discuss seminal studies examining sex differences in hippocampal memory, neuronal morphology, synaptic plasticity, and cell signaling in humans and rodents. We also describe possible organizational and activational effects of sex steroid hormones during early development, puberty, and adulthood that may lead to sex differences observed in the hippocampus. We conclude by discussing the implications of sex differences in hippocampal function for mental health. © 2016 Wiley Periodicals, Inc.
Sex differences in neural responses to subliminal sad and happy faces in healthy individuals: Implications for depression
Authors: Victor Teresa A. , Drevets Wayne C. , Misaki Masaya , Bodurka Jerzy , Savitz Jonathan
Published: November 2016

Twice as many women as men suffer from mood and anxiety disorders, yet the biological underpinnings of this phenomenon have been understudied and remain unclear. We and others have shown that the hemodynamic response to subliminally presented sad or happy faces during functional MRI (fMRI) is a robust biomarker for the attentional bias toward negative information classically observed in major depression. Here we used fMRI to compare the performance of healthy females (n = 28) and healthy males (n = 28) on a backward masking task using a fast event‐related design with gradient‐recalled, echoplanar imaging with sensitivity encoding. The image data were compared across groups using a region‐of‐interest analysis with small‐volume correction to control for multiple testing (Pcorrected < 0.05, cluster size ≥ 20 voxels). Notably, compared with males, females showed greater BOLD activity in the subgenual anterior cingulate cortex (sgACC) and the right hippocampus when viewing masked sad vs. masked happy faces. Furthermore, females displayed reduced BOLD activity in the right pregenual ACC and left amygdala when viewing masked happy vs. masked neutral faces. Given that we have previously reported similar findings for depressed participants compared with healthy controls (regardless of gender), our results raise the possibility that on average healthy females show subtle emotional processing biases that conceivably reflect a subgroup of women predisposed to depression. Nevertheless, we note that the differences between males and females were small and derived from region‐of‐interest rather than voxelwise analyses. © 2016 Wiley Periodicals, Inc.
Understanding the epigenetic basis of sex differences in depression
Authors: Hodes Georgia E. , Walker Deena M. , Labonté Benoit , Nestler Eric J. , Russo Scott J.
Published: November 2016

Epigenetics refers to potentially heritable processes that can mediate both lasting and transient changes in gene expression in the absence of genome sequence alterations. The field of epigenetics has introduced a novel understanding of the mechanisms through which the environment can shape an individual and potentially its offspring. This Mini‐Review examines the current literature exploring the role of epigenetics in the development of mood disorders such as depression. Depression is twofold more common in females, yet the majority of preclinical research has been conducted exclusively in male subjects. Here we discuss what is known about sex differences in epigenetic regulation and function and how this may contribute to the etiology and onset of mood disorders. © 2016 Wiley Periodicals, Inc.
Magnetoencephalography study of different relationships among low‐ and high‐frequency‐band neural activities during the induction of peaceful and fearful audiovisual modalities among males and females
Authors: Yang Chia‐Yen , Lin Ching‐Po
Published: November 2016

Our previous study estimated the bias from the match attributes of the auditory and visual modalities related to a peaceful mood in the male brain. However, the interactions among the four main frequency bands of neural activity remain unknown. Therefore, this study uses magnetoencephalography to explore gender differences in the perceptions of auditory and visual modalities related to peaceful and fearful moods. Instead of analyzing single frequencies, this study analyzes interactions between low‐frequency phase and high‐frequency amplitude to reflect neural communication. The top four values in each of the 10 brain regions were averaged to give a representative value for further analysis with repeated‐measures ANOVA. The results from the cross‐frequency analyses suggest that delta–theta, delta–alpha, delta–beta, and delta–gamma couplings are associated with interactions between emotion and modality; theta–alpha, theta–beta, and theta–gamma couplings are associated with interactions between gender and emotion/time; alpha–beta and alpha–gamma couplings are associated with time; and beta–gamma coupling is associated with interactions between gender and modality. Although no obvious hemispheric lateralization of emotion in the macroscopic neural activity was found, these results reveal that males have stronger couplings (e.g., beta–gamma coupling) in the visual modality related to peaceful mood, whereas females have stronger couplings (e.g., beta–gamma coupling) in the audiovisual modality related to fearful mood. Gender differences become much more apparent when analysis is based on cross‐frequency coupling. © 2016 Wiley Periodicals, Inc.
Sex differences in the human visual system
Authors: Vanston John E. , Strother Lars
Published: November 2016

This Mini‐Review summarizes a wide range of sex differences in the human visual system, with a primary focus on sex differences in visual perception and its neural basis. We highlight sex differences in both basic and high‐level visual processing, with evidence from behavioral, neurophysiological, and neuroimaging studies. We argue that sex differences in human visual processing, no matter how small or subtle, support the view that females and males truly see the world differently. We acknowledge some of the controversy regarding sex differences in human vision and propose that such controversy should be interpreted as a source of motivation for continued efforts to assess the validity and reliability of published sex differences and for continued research on sex differences in human vision and the nervous system in general. © 2016 Wiley Periodicals, Inc.
Sex/gender influences on the nervous system: Basic steps toward clinical progress
Authors: Brooks Claudette Elise , Clayton Janine Austin
Published: November 2016

A Commentary highlighting the progress that sex‐based data and research have made in neuroscience and the complexities that research has revealed thus far. Basic and preclinical neuroscientific research that considers sex as a biological variable will continue to build on the foundation of knowledge that has been started by multiple predecessors. The expansion of knowledge in preclinical neuroscience that integrates the study of both sexes will have a significant role in informing clinical trial design. We applaud the efforts of the editors and authors who have contributed to this issue. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Sex differences in neuroinflammation and neuroprotection in ischemic stroke
Authors: Spychala Monica S. , Honarpisheh Pedram , McCullough Louise D.
Published: November 2016

Stroke is not only a leading cause of mortality and morbidity worldwide it also disproportionally affects women. There are currently over 500,000 more women stroke survivors in the US than men, and elderly women bear the brunt of stroke‐related disability. Stroke has dropped to the fifth leading cause of death in men, but remains the third in women. This review discusses sex differences in common stroke risk factors, the efficacy of stroke prevention therapies, acute treatment responses, and post‐stroke recovery in clinical populations. Women have an increased lifetime risk of stroke compared to men, largely due to a steep increase in stroke incidence in older postmenopausal women, yet most basic science studies continue to only evaluate young male animals. Women also have an increased lifetime prevalence of many common stroke risk factors, including hypertension and atrial fibrillation, as well as abdominal obesity and metabolic syndrome. None of these age‐related risk factors have been well modeled in the laboratory. Evidence from the bench has implicated genetic and epigenetic factors, differential activation of cell‐death programs, cell‐cell signaling pathways, and systemic immune responses as contributors to sex differences in ischemic stroke. The most recent basic scientific findings have been summarized in this review, with an emphasis on factors that differ between males and females that are pertinent to stroke outcomes. Identification and understanding of the underlying biological factors that contribute to sex differences will be critical to the development of translational targets to improve the treatment of women after stroke. © 2016 Wiley Periodicals, Inc.
Solid‐phase nanoextraction of polychlorinated biphenyls in water and their determination by gas chromatography with electron capture detector
Authors: Piramoon Shadi , Aberoomand Azar Parviz , Saber Tehrani Mohammad , Mohammadiazar Sirwan , Tavassoli Abdollah
Published: November 2016

A solid‐phase nanoextraction method has been developed for the extraction and preconcentration of polychlorinated biphenyls using carboxyl multiwalled carbon nanotubes as a solid nano‐sorbent. Parameters affecting extraction efficiency such as sorbent amount, desorption solvent type and volume, extraction time, pH, and salt content have been studied. Under optimized conditions, the correlation coefficient was up to 0.9989, the limits of detection was in the range of 1.4–3.5 ng/L, and limits of quantification was between 4.8 and 11.6 ng/L. The recoveries were in the range of 99–106% for different spiked analytes. The relative standard deviation for water samples spiked with two different spiking levels has been between 4 and 10%. The proposed sustainable method is rapid, easy to use, and small consumption of organic solvent for the detection and determination of trace levels of polychlorinated biphenyls in environmental waters.
The Synechococcus cell surface protein SwmA increases vulnerability to predation by flagellates and ciliates
Authors: Strom Suzanne , Bright Kelley , Fredrickson Kerri , Brahamsha Bianca
Published: November 2016

The genus Synechococcus, a major contributor to ocean productivity, exhibits wide genetic variability and a distinct biogeography of genetic subgroups. Synechococcus sp. strain WH8102 is a motile Sargasso Sea isolate belonging to Clade III in subcluster 5.1. Non‐flagellar motility in WH8102 depends upon two large cell surface proteins, SwmA and SwmB. In the marine plankton, Synechococcus can experience high rates of mortality from protist predators, suggesting strong selective pressure for the maintenance of anti‐predation defenses. We used knockout mutants deficient in large cell surface proteins (SwmA‐ and SwmB‐) to test the hypothesis that these proteins defend WH8102 against predation by ciliates and flagellates, important consumers of Synechococcus in aquatic ecosystems. Contrary to our hypothesis, we found that wild‐type WH8102 were preyed upon at higher rates than SwmA‐ by ciliates and by two of three tested flagellate species. Thus the SwmA protein, constitutively produced by WH8102, made this strain more rather than less vulnerable to predation. SwmA proteins link to form the S layer, a cell coating known to promote adhesion in other microbial systems, suggesting the predation vulnerability arises from increased attachment between consumers and prey. Given the SwmA‐related enhancement of predation rates, our findings suggest two possibilities for WH8102 and perhaps other Clade III Synechococcus: (1) factors other than protist predation select for production of the S layer; (2) ingestion actually increases fitness, by exposing digestion‐resistant cells to beneficial conditions in the food vacuole.
Influence of hydrogen bubbles adhering to the exposed surface on the corrosion rate of magnesium alloys AZ31 and AZ61 in sodium chloride solution
Authors: Feliu S. , García‐Galvan F. R. , Llorente I. , Diaz L. , Simancas J.
Published: November 2016

The influence of the presence of hydrogen bubbles adhered to the corroding specimen surface on the EIS estimations of corrosion rate of magnesium alloys is considered. The EIS corrosion rates for AZ31 specimens exposing a small area were four times higher than the real values determined by gravimetric or hydrogen evolution measurements. In contrast, no significant differences in the corrosion rate have been observed in the case of the AZ61 specimens. A progressive deterioration in the protective properties of the corrosion products layer formed during the test was observed only on AZ31 specimens exposing a small area.
Kinetic Control of Block Copolymer Self‐Assembly in a Micromixing Device – Mechanistical Insight into Vesicle Formation Process
Authors: Thiermann Raphael , Bleul Regina , Maskos Michael
Published: November 2016

Control over the self‐assembly process plays a crucial role in the synthesis of supramolecular structures. In this study, the formation of block copolymer vesicles from poly(butadiene)‐block‐poly(ethyleneoxide) is extensively investigated and analyzed. It is shown how the application of micromixer technology enables not only to control the aggregate size but also to allow trapping thermodynamic instable intermediates during the vesicle formation. Anisotropic disk‐like polymer aggregates are identified by cryo‐TEM (transmission electron microscopy) measurements by tilting the TEM sample holder. These disk‐like micelles represent the precursors of vesicles that form the final spherical hollow spheres by closing up. These intermediates help to gain valuable insight into the self‐assembly mechanism, which is of great importance, e.g., for the successful encapsulation of hydrophilic particles and molecules into vesicular structures for targeted drug delivery. Kinetic control during self‐assembly of amphiphiles in the micromixer device also accomplishes access to highly defined polymer aggregate structures of distinct size and morphology.

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Kinetics and Modeling of the Radical Polymerization of Trimethylaminoethyl methacrylate chloride in Aqueous Solution
Authors: Drawe Patrick , Kattner Hendrik , Buback Michael
Published: November 2016

For the radical polymerization of ionized trimethylaminoethyl methacrylate chloride (TMAEMA) in aqueous solution, two strategies to determine the propagation rate coefficient (kp) are proposed for systems where the pulsed‐laser polymerization–size‐exclusion chromatography (PLP–SEC) method fails. This problem occurs with some fully ionized or sterically highly hindered monomers, where termination may become too slow. As TMAEMA is a borderline case withkpbeing accessible by PLP–SEC and from single‐pulse–pulsed‐laser polymerization with electron paramagnetic resonance (SP–PLP–EPR) spectroscopy, studies into this monomer allow for judging the quality of the suggested alternative approaches ofkpmeasurement and serve for consistency checks of the previously publishedkpand termination rate coefficient (kt) data. Within both approaches,kp/〈kt〉0.5is measured via chemically initiated polymerization, with 〈kt〉 referring to chain‐length‐averaged termination. Thekp/〈kt〉0.5data are combined either withkp/〈kt〉 values from highly time‐resolved near‐infrared detection of monomer conversion induced by a single laser pulse (SP–PLP–NIR) or with Predici modeling on the basis of known chain‐length‐dependent termination kinetics. As coupled rate coefficients are measured, the obtainedkpdata also provide 〈kt〉 for a particular chain‐length distribution. The differences between propagation and termination rates of nonionized and fully ionized monomers are discussed.

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Stromal contributions to the carcinogenic process
Authors: Spaw Mark , Anant Shrikant , Thomas Sufi Mary
Published: November 2016

Tumor‐associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non‐cellular components. Tumor‐associated stromal cell types include the microbiome, immune cells including macrophages, dendritic and T‐cells, cells associated with blood and lymphatic vessels including pericytes and endothelial cells, fibroblasts, neuronal cells, and adipocytes. The non‐cellular components of the microenvironment include matrix proteins and secreted factors. The development of therapies that target the mechanisms by which stromal cells contribute to successful tumorigenesis is major goal of upcoming cancer research. The purpose of this review is to present a comprehensive discussion of the role of each of the tumor‐associated stromal cell types in the carcinogenic process with a special focus on target development and therapeutic intervention. © 2016 Wiley Periodicals, Inc.
Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients
Authors: Spataro Nino , Roca‐Umbert Ana , Cervera‐Carles Laura , Vallès Mònica , Anglada Roger , Pagonabarraga Javier , Pascual‐Sedano Berta , Campolongo Antònia , Kulisevsky Jaime , Casals Ferran , Clarimón Jordi , Bosch Elena
Published: November 2016

Background

The analysis of coverage depth in next‐generation sequencing data allows the detection of gene dose alterations. We explore the frequency of such structural events in a Spanish cohort of sporadic PD cases.

Methods

Gene dose alterations were detected with the eXome‐Hidden Markov Model (XHMM) software from depth of coverage in resequencing data available for 38 Mendelian and other risk PD loci in 394 individuals (249 cases and 145 controls) and subsequently validated by quantitative PCR.

Results

We identified 10 PD patients with exon dosage alterations in PARK2, GBA‐GBAP1, and DJ1. Additional functional variants, including 2 novel nonsense mutations (p.Arg1552Ter in LRRK2 and p.Trp90Ter in PINK1), were confirmed by Sanger sequencing. This combined approach disclosed the genetic cause of 12 PD cases.

Conclusions

Gene dose alterations related to PD can be correctly identified from targeting resequencing data. This approach substantially improves the detection rate of cases with causal genetic alterations. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Controllability of a class of heat equations with memory in one dimension
Authors: Zhou Xiuxiang , Gao Hang
Published: November 2016

This paper addresses a study of the controllability for a class of heat equations with memory in one spacial dimension. Unlike the classical heat equation, a heat equation with memory in general is not null controllable. There always exists a set of initial values such that the property of the null controllability fails. Also, one does not know whether there are nontrivial initial values, which can be driven to zero with a boundary control. In this paper, we give a characterization of the set of such nontrivial initial values. On the other hand, if a moving control is imposed on this system with memory, we prove the null controllability of it in a suitable state space for any initial value. Copyright © 2016 John Wiley & Sons, Ltd.
Curcumin improves glucose tolerance via stimulation of glucagon‐like peptide‐1 secretion
Authors: Kato Masaki , Nishikawa Sho , Ikehata Akiho , Dochi Kojiro , Tani Tsubasa , Takahashi Tsukasa , Imaizumi Atsushi , Tsuda Takanori
Published: November 2016

Scope

Glucagon‐like peptide‐1 (GLP‐1) is a type of incretin secreted from enteroendocrine L‐cells. Our previous studies demonstrated that curcumin (a yellow pigment of turmeric) significantly increases the secretion of GLP‐1 in enteroendocrine L cell line (GLUTag cells). However, it is not clear whether its action in vivo directly enhances GLP‐1 secretion, which then leads to a reduction in blood glucose levels via the stimulation of insulin secretion. In addition, the molecular target of curcumin‐induced GLP‐1 secretion has not been clarified.

Methods and results

Glucose tolerance was significantly improved in rats after pre‐administered curcumin (1.5 mg/kg) followed by intraperitoneal glucose injections via the stimulation of GLP‐1 secretion and the induction of insulin secretion. In GLUTag cells, curcumin‐induced GLP‐1 secretion was associated with G protein‐coupled receptor (GPR) 40/120. Furthermore, the glucose‐lowering effect induced by curcumin was significantly reduced after the administration of a GPR40/120 antagonist in rats.

Conclusion

These findings demonstrate the biological function of curcumin as a GLP‐1 secretagogue and the possible molecular target that mediates GLP‐1 secretion. Increases in the secretion of endogenous GLP‐1 induced by curcumin may allow the dosages of other diabetic medicines to be reduced and aid in the prevention of diabetes.
Stereotactic body radiotherapy for pediatric hepatocellular carcinoma with central biliary obstruction
Authors: Hiniker Susan M. , Rangaswami Arun , Lungren Matthew P. , Thakor Avnesh S. , Concepcion Waldo , Balazy Kathleen E. , Kovalchuk Nataliya , Donaldson Sarah S.
Published: November 2016

Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma causing central biliary obstruction and persistently elevated bilirubin of 3.0–4.3 mg/dl despite placement of bilateral internal–external biliary drains. The tumor was not resectable, and the patient was not a candidate for liver transplant due to nodal disease, for chemotherapy due to hyperbilirubinemia, or for local therapies aside from stereotactic body radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the management of this patient, and its role in allowing the patient to become a candidate for additional therapies.
Potential Association between Drug Shortages and High‐Cost Medications
Authors: Fox Erin R. , Tyler Linda S.
Published: November 2016

Shortages and sudden price increases of certain drugs may both occur emergently, with little to no warning, and they can have a dramatic impact on patient care. Little data are available linking drug shortages and price increases. Many of the same characteristics that may make medications susceptible to shortages can also place them at risk for sudden price increases. These characteristics include unapproved drugs, off‐patent sole‐source medications, and infrequently used medications. We reviewed drug shortage data from the University of Utah Drug Information Service to demonstrate how frequently these characteristics occurred and resulted in higher drug prices. Clinicians can use drug shortage management principles to mitigate the impact of sudden price increases for patients and health care organizations.
Managing the Rising Costs and High Drug Expenditures in Critical Care Pharmacy Practice
Authors: Flannery Alexander H. , Pandya Komal , Laine Melanie E. , Almeter Philip J. , Flynn Jeremy D.
Published: November 2016

Pharmaceutical costs for patients in the intensive care unit (ICU) constitute a large portion of hospital drug budgets. Unfortunately, prices for medications commonly used in the ICU are on the rise for a variety of reasons. In particular, the U.S. Food and Drug Administration's Unapproved Drugs Initiative, generic manufacturers cornering the marketplace, drug shortages, and regulatory device changes are major drivers of pharmaceutical price escalation affecting costs in the ICU. Furthermore, traditional high acquisition cost items still pose challenges to controlling costs. To offer strategies to mitigate the rising costs of pharmaceuticals in the ICU setting, we searched the PubMed/Medline and International Pharmaceutical Abstracts databases and other related sources to identify published cost‐saving protocols concerning specific medications that are affected by rising prices or have traditional high acquisition costs. In the absence of specific protocols, we offer possible cost‐saving initiatives based on published literature regarding specific agents or based on our own diverse set of experiences. Finally, we review suggested clinical and operational activities at an institutional level to address these rising drug costs in the ICU setting.
Modeling of a Non‐Thermal RF Plasma Jet at Atmospheric Pressure
Authors: Sigeneger Florian , Schäfer Jan , Weltmann Klaus‐Dieter , Foest Rüdiger , Loffhagen Detlef
Published: November 2016

An RF driven non‐thermal atmospheric pressure plasma jet used for plasma enhanced chemical vapor deposition is investigated by hydrodynamic modeling. The model describes the gas flow and heating, the plasma generation in the active zone, reactions of active plasma particles with precursor molecules in the effluent, and the transport of precursor fragments toward the substrate. Molecular argon ions are found to be the dominant active species transported into the effluent together with slow electrons. The radial profiles of the fluxes of precursor fragments onto the substrate depend sensitively on the flow conditions. Satisfactory agreement of the calculated gas temperature with measured profiles is obtained.
Concepts, Capabilities, and Limitations of Global Models: A Review
Authors: Hurlbatt Andrew , Gibson Andrew Robert , Schröter Sandra , Bredin Jérôme , Foote Alexander Paul Stuart , Grondein Pascaline , O'Connell Deborah , Gans Timo
Published: November 2016

For researchers wishing to generate an understanding of complex plasma systems, global models often present an attractive first step, mainly due to their ease of development and use. These volume averaged models are able to give descriptions of plasmas with complex chemical kinetics, and without the computationally intensive numerical methods required for spatially resolved models. This paper gives a tutorial on global modeling, including development and techniques, and provides a discussion on the issues and pitfalls that researchers should be aware of. Further discussion is provided in the form of two reviews on methods of extending global modeling techniques to encompass variations in either time or space.
A Comparative Study of Chemical Routes for Coating Gold Nanoparticles via Controlled RAFT Emulsion Polymerization
Authors: Pereira Sónia O. , Barros‐Timmons Ana , Trindade Tito
Published: November 2016

The synthesis of core‐shell Au nanoparticles protected by an amphiphilic block copolymer is investigated by distinct reversible addition fragmentation chain transfer (RAFT) emulsion polymerization routes. The controlled polymerization of polymer shells onto Au nanoparticles is attempted by using the macroRAFT (MR) agent based on 2‐(dodecylthiocarbonothioylthio)‐2‐methylpropionic acid synthesized via RAFT polymerization of poly(ethylene glycol) methyl ether acrylate and exploring several approaches, which include (i) post‐modification; (ii) in situ synthesis and (iii) “grafting from” strategies. In the conditions investigated here all these strategies lead to Au polymer nanocomposites but morphological well‐defined core‐shell nanoparticles are only obtained by applying the “grafting from” strategy. In particular, conditions that promote chain extension from the MR agent adsorbed onto the Au nanoparticles are found necessary to obtain nanostructures with such morphological characteristics and that still show the localized surface plasmon resonance typical of colloidal Au nanoparticles.
Characterization of Phase I and Phase II Hepatic Metabolism and Reactive Intermediates of Larrea nitida Cav. and Its Lignan Compounds
Authors: Jeong Hyesoo , Kim Soolin , Lee Jimin , Park Jin Young , Zhou Wenmei , Liu Xiyuan , Kim So Dam , Song Yun Seon , Jang Chang‐Young , Oh Sei‐Ryang , Choi Sangho , Chang Minsun
Published: November 2016

Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America to treat various pathological conditions. It contains the antioxidant and antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well as O‐methylated metabolite of NDGA (MNDGA) as bioactive compounds. The hepatic metabolism‐based toxicological potential of extracts of LNC (LNE), NDGA, and MNDGA has not previously been reported. The present study aimed to characterize the phase I and phase II hepatic metabolism and reactive intermediates of LNE, NDGA, and MNDGA and their effects on the major drug‐metabolizing enzymes in vitro and ex vivo. A methanol extract of LNC collected from Chile as well as NDGA and MNDGA isolated from LNE were subjected to metabolic stability assays in liver microsomes in the presence of the cofactors reduced nicotinamide dinucleotide phosphate (NADPH) and/or uridine 5′‐diphosphoglucuronic acid (UDPGA). Cytochrome P450 (CYP) inhibition assays were performed using CYP isozyme‐specific model substrates to examine the inhibitory activities of LNE, NDGA, and MNDGA, which were expressed as % inhibition and IC50 values. Ex vivo CYP induction potential was investigated in the liver microsomes prepared from the rats intraperitoneally administered with LNE. Glutathione (GSH) adduct formation was monitored by LC‐MS3 analysis of the microsomal incubation samples with either NDGA or MNDGA and an excess of GSH to determine the formation of electrophilic reactive intermediates. Both NDGA and MNDGA were stable to NADPH‐dependent phase I metabolism, but labile to glucuronide conjugation. LNE, NDGA, and MNDGA showed significant inhibitory effects on CYP1A2, 2C9, 2D6, and/or 3A4, with IC50 values in the micromolar range. LNE was found to be a CYP1A2 inducer in ex vivo rat experiments, and mono‐ and di‐GSH adducts of both NDGA and MNDGA were identified by LC‐MS3 analysis. Our study suggests that hepatic clearance is the major elimination route for the lignans NDGA and MNDGA present in LNE. These lignans may possess the ability to modify biomacromolecules via producing reactive intermediates. In addition, LNE, NDGA, and MNDGA are found to be inhibitors for various CYP isozymes such as CYP2C9 and 3A4. Thus, the consumption of LNC as an herbal preparation or NDGA may cause metabolism‐driven herb–drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.