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Σάββατο 11 Φεβρουαρίου 2017

fMRI study of the role of glutamate NMDA receptor in the olfactory adaptation in rats: Insights into cellular and molecular mechanisms of olfactory adaptation

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Fuqiang Zhao, Xiaohai Wang, Hatim A. Zariwala, Jason M. Uslaner, Andrea K. Houghton, Jeffrey L. Evelhoch, Eric Hostetler, Christopher T. Winkelmann, Catherine D.G. Hines
Olfactory adaptation, characterized by attenuation of response to repeated odor stimulations or continuous odor exposure, is an intrinsic feature of olfactory processing. Adaptation can be induced by either "synaptic depression" due to depletion of neurotransmitters, or "enhanced inhibition" onto principle neurons by local inhibitory interneurons in olfactory structures. It is not clear which mechanism plays a major role in olfactory adaptation. More importantly, molecular sources of enhanced inhibition have not been identified. In this study, olfactory responses to either repeated 40-s stimulations with interstimulus intervals (ISI) of 140-s or 30-min, or a single prolonged 200-s stimulus were measured by fMRI in different naïve rats. Olfactory adaptations in the olfactory bulb (OB), anterior olfactory nucleus (AON), and piriform cortex (PC) were observed only with repeated 40-s odor stimulations, and no olfactory adaptations were detected during the prolonged 200-s stimulation. Interestingly, in responses to repeated 40-s odor stimulations in the PC, the first odor stimulation induced positive activations, and odor stimulations under adapted condition induced negative activations. The negative activations suggest that "sparse coding" and "global inhibition" are the characteristics of olfactory processing in PC, and the global inhibition manifests only under an adapted condition, not a naïve condition. Further, we found that these adaptations were NMDA receptor dependent; an NMDA receptor antagonist (MK801) blocked the adaptations. Based on the mechanism that glutamate NMDA receptor plays a role in the inhibition onto principle neurons by interneurons, our data suggest that the olfactory adaptations are caused by enhanced inhibition from interneurons. Combined with the necessity of the interruption of odor stimulation to observe the adaptations, the molecular source for the enhanced inhibition is most likely an increased glutamate release from presynaptic terminals due to glutamate over-replenishment during the interruption of odor stimulation. Furthermore, with blockage of the adaptations, the data reveal that orbital, medial & prefrontal, and cingulate cortices (OmPFC) are involved in the olfactory processing.



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Decoded fMRI neurofeedback can induce bidirectional confidence changes within single participants

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Aurelio Cortese, Kaoru Amano, Ai Koizumi, Hakwan Lau, Mitsuo Kawato
Neurofeedback studies using real-time functional magnetic resonance imaging (rt-fMRI) have recently incorporated the multi-voxel pattern decoding approach, allowing for fMRI to serve as a tool to manipulate fine-grained neural activity embedded in voxel patterns. Because of its tremendous potential for clinical applications, certain questions regarding decoded neurofeedback (DecNef) must be addressed. Specifically, can the same participants learn to induce neural patterns in opposite directions in different sessions? If so, how does previous learning affect subsequent induction effectiveness? These questions are critical because neurofeedback effects can last for months, but the short- to mid-term dynamics of such effects are unknown. Here we employed a within-subjects design, where participants underwent two DecNef training sessions to induce behavioural changes of opposing directionality (up or down regulation of perceptual confidence in a visual discrimination task), with the order of training counterbalanced across participants. Behavioral results indicated that the manipulation was strongly influenced by the order and the directionality of neurofeedback training. We applied nonlinear mathematical modeling to parametrize four main consequences of DecNef: main effect of change in confidence, strength of down-regulation of confidence relative to up-regulation, maintenance of learning effects, and anterograde learning interference. Modeling results revealed that DecNef successfully induced bidirectional confidence changes in different sessions within single participants. Furthermore, the effect of up- compared to down-regulation was more prominent, and confidence changes (regardless of the direction) were largely preserved even after a week-long interval. Lastly, the effect of the second session was markedly diminished as compared to the effect of the first session, indicating strong anterograde learning interference. These results are interpreted in the framework of reinforcement learning and provide important implications for its application to basic neuroscience, to occupational and sports training, and to therapy.



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Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Catherine Fassbender, Prerona Mukherjee, Julie B. Schweitzer
Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies.



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Selective TMS-induced modulation of functional connectivity correlates with changes in behavior

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Puiu F. Balan, Annelies Gerits, Dante Mantini, Wim Vanduffel
Despite the increasing use of functional connectivity (FC) studies in fundamental and clinical research, the link between FC and behavior is still poorly understood. To test the hypothesis that artificial modulation of FC correlates with changes in behavior in a quantitative manner, we performed behavioral and resting state fMRI experiments in monkeys while perturbing, offline, the frontal eye fields (FEF) using unilateral continuous theta burst transcranial magnetic stimulation (FEF-cTBS). Stimulation of left and right FEF caused remarkably specific decreases in FC, which were symmetric for intra-hemispheric and asymmetric for inter-hemispheric FC. Surprisingly, FEF-cTBS improved the performance and compensated intrinsic choice biases in saccadic behavior of four monkeys, independent of the initial bias direction. Moreover, the direction of the stimulation-induced effects on both behavior (i.e. bias compensation) and FC (i.e. decrease) were independent of the stimulated hemisphere, while their magnitude depended on the side of stimulation, choice bias and monkey. Overall, the naturally-occurring saccade biases determined the FC changes following FEF-cTBS. Finally, we showed that the average decreases in FC in the FEF network induced by cTBS can be used to predict, with high specificity, both the direction (opposite to the saccadic biases) and the magnitude of the shift in saccadic choice preference relative to the unperturbed state. To reconcile the apparent contradiction between improved performance and bias compensation vs. decrease in functional connectivity, we propose that the main functional consequences of FEF-cTBS relate to adjusting inter-hemispheric imbalances.



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Parallel changes in cortical neuron biochemistry and motor function in protein-energy malnourished adult rats

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Mariam Alaverdashvili, Mark J. Hackett, Sally Caine, Phyllis G. Paterson
While protein-energy malnutrition in the adult has been reported to induce motor abnormalities and exaggerate motor deficits caused by stroke, it is not known if alterations in mature cortical neurons contribute to the functional deficits. Therefore, we explored if PEM in adult rats provoked changes in the biochemical profile of neurons in the forelimb and hindlimb regions of the motor cortex. Fourier transform infrared spectroscopic imaging using a synchrotron generated light source revealed for the first time altered lipid composition in neurons and subcellular domains (cytosol and nuclei) in a cortical layer and region-specific manner. This change measured by the area under the curve of the δ(CH2) band may indicate modifications in membrane fluidity. These PEM-induced biochemical changes were associated with the development of abnormalities in forelimb use and posture. The findings of this study provide a mechanism by which PEM, if not treated, could exacerbate the course of various neurological disorders and diminish treatment efficacy.



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Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Gong-Jun Ji, Fengqiong Yu, Wei Liao, Kai Wang
The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies.



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Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson’s disease patients with defined cholinergic losses

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Kamin Kim, Martijn L.T.M. Müller, Nicolaas I. Bohnen, Martin Sarter, Cindy Lustig
Successful behavior depends on the ability to detect and respond to relevant cues, especially under challenging conditions. This essential component of attention has been hypothesized to be mediated by multiple neuromodulator systems, but the contributions of individual systems (e.g., cholinergic, dopaminergic) have remained unclear. The present study addresses this issue by leveraging individual variation in regionally-specific cholinergic denervation in Parkinson's disease (PD) patients, while controlling for variation in dopaminergic denervation. Patients whose dopaminergic and cholinergic nerve terminal integrity had been previously assessed using Positron Emission Tomography (Bohnen et al., 2012) and controls were tested in a signal detection task that manipulates attentional-perceptual challenge and has been used extensively in both rodents and humans to investigate the cholinergic system's role in responding to such challenges (Demeter et al., 2008; McGaughy and Sarter, 1995; see Hasselmo and Sarter 2011 for review). In simple correlation analyses, measures of midbrain dopaminergic, and both cortical and thalamic cholinergic innervation all predicted preserved signal detection under challenge. However, regression analyses also controlling for age, disease severity, and other variables showed that the only significant independent neurotransmitter-related predictor over and above the other variables in the model was thalamic cholinergic integrity. Furthermore, thalamic cholinergic innervation exclusively predicted hits, not correct rejections, indicating a specific contribution to bottom-up salience processing. These results help define regionally-specific contributions of cholinergic function to different aspects of attention and behavior.



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Age-dependent atypicalities in body- and face-sensitive activation of the EBA and FFA in individuals with ASD

Publication date: Available online 11 February 2017
Source:Neuroscience Research
Author(s): Yuko Okamoto, Hirotaka Kosaka, Ryo Kitada, Ayumi Seki, Hiroki C. Tanabe, Masamichi J. Hayashi, Takanori Kochiyama, Daisuke N. Saito, Hisakazu T. Yanaka, Toshio Munesue, Makoto Ishitobi, Masao Omori, Yuji Wada, Hidehiko Okazawa, Tatsuya Koeda, Norihiro Sadato
Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene. To examine various aspects, we performed individual region of interest (ROI) analysis, as well as conventional random effect group analysis. At individual ROI analysis, we examined the ratio of participants showing a category-sensitive response, the size of regions, location and activation patterns among the four object categories. Adults with ASD showed no atypicalities in activation of the EBA and FFA, whereas children with ASD showed atypical activation in these regions. Specifically, a smaller percentage of children with ASD showed face-sensitive activation of the FFA than TD children. Moreover, the size of the EBA was smaller in children with ASD than in TD children. Our results revealed atypicalities in both the FFA and EBA in children with ASD but not in adults with ASD.



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Mutation of a putative MAP kinase consensus site regulates NCAM endocytosis and NCAM-dependent neurite outgrowth

Publication date: Available online 11 February 2017
Source:Neuroscience Research
Author(s): Tobias Goschzik, Harold Cremer, Vinayaga S. Gnanapragassam, Rüdiger Horstkorte, Kaya Bork, Simone Diestel
The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites whose functions are largely unknown. Human NCAM140 (NCAM140) possesses a potential MAP kinase phosphorylation site at threonine (T) 803. The aim of this study was to analyze a possible phosphorylation of NCAM140 by MAP kinases and to identify the functional role of T803. We found that NCAM140 is phosphorylated by the MAP kinase ERK2 in vitro. Exchange of T803 to aspartic acid (D) which mimics constitutive phosphorylation at the respective position resulted in increased endocytosis compared to NCAM140 in neuroblastoma cells and primary neurons. Consistently, NCAM140 endocytosis was inhibited by the MEK inhibitor U0126 in contrast to NCAM140-T803D or NCAM140-T803A endocytosis supporting a role of a potential ERK2 mediated phosphorylation at this site in endocytosis. Furthermore, cells expressing NCAM140-T803D developed significantly shorter neurites than NCAM140 expressing cells indicating that a potential phosphorylation of NCAM by ERK2 also regulates NCAM-dependent neurite outgrowth.



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Calcium-binding protein, secretagogin, characterizes novel groups of interneurons in the rat striatum

Publication date: Available online 11 February 2017
Source:Neuroscience Research
Author(s): Toshio Kosaka, Seiko Yasuda, Katsuko Kosaka
In the rat striatum numerous secretagogin (SCGN) positive neurons were scattered. They were heterogeneous in their morphological and chemical properties. We examined the colocalization of SCGN with known four interneuron markers, parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) and choline acetyl transferase (ChAT). 60-70% of SCGN positive striatal neurons contained either PV or CR or ChAT, but none contained NOS. On the other hand the remaining 30-40% expressed none of these markers, most of which were GAD positive. The present study indicates that there are hitherto unknown groups of striatal interneurons in the rat striatum.



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Metabolomics: A Primer

Publication date: Available online 11 February 2017
Source:Trends in Biochemical Sciences
Author(s): Xiaojing Liu, Jason W. Locasale
Metabolomics generates a profile of small molecules that are derived from cellular metabolism and can directly reflect the outcome of complex networks of biochemical reactions, thus providing insights into multiple aspects of cellular physiology. Technological advances have enabled rapid and increasingly expansive data acquisition with samples as small as single cells; however, substantial challenges in the field remain. In this primer we provide an overview of metabolomics, especially mass spectrometry (MS)-based metabolomics, which uses liquid chromatography (LC) for separation, and discuss its utilities and limitations. We identify and discuss several areas at the frontier of metabolomics. Our goal is to give the reader a sense of what might be accomplished when conducting a metabolomics experiment, now and in the near future.



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Photoprotection in specific populations: Children and people of color

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1
Author(s): Tania Cestari, Kesha Buster
Improved education on appropriate photoprotection in children is vital. Photoprotection for these individuals should include seeking shade, the use of physical agents (clothing, hat, sunglasses), and application of sunscreens on exposed areas. Avoidance of the use of tanning beds is an important component of education for teenagers. Ultraviolet radiation exposure induces DNA damage and photoaging in all skin types, including people of color. The extent of such damage is inversely related to constitutive skin pigmentation. Therefore, personalized photoprotection recommendations concerning skin cancer risk factors, desired treatment outcomes, health needs (eg, vitamin D), and photoaging based on the needs and preferences of the patient are essential. It is clear that additional research is needed on optimal levels of protection against ultraviolet radiation for people of color.



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Table of Contents

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1





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Editorial Board

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1





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Challenges in photoprotection: Introduction

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1
Author(s): Henry W. Lim




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Current challenges in photoprotection

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1
Author(s): Henry W. Lim, Maria-Ivonne Arellano-Mendoza, Fernando Stengel
Electromagnetic radiation in the ultraviolet, visible, and infrared ranges all produce biologic effects. Ultraviolet filters are the most well-studied photoprotective measure for the adverse effects of ultraviolet radiation. Because of the reported endocrinologic effects of oxybenzone in animal studies, its effects on coral reefs, and its photocontact allergy potential, its use has been minimized in many countries worldwide. New developments in topical antioxidants and oral and subcutaneous agents (eg, Polypodium leucotomos extract, afamelanotide, nicotinamide) with photoprotective and antiphotocarcinogenic properties could potentially provide addition modalities for protection against the effects of visible light and infrared radiation.



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Ultraviolet radiation and the skin: Photobiology and sunscreen photoprotection

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1
Author(s): Antony R. Young, Joël Claveau, Ana Beatris Rossi
The efficacy of sunscreens can be measured by different methods, involving in vitro, ex vivo, or in vivo techniques. There is a need for a worldwide standardization of these methods to avoid misunderstanding and confusion among sunscreen users. The clinical benefits of sunscreens have been demonstrated in randomized controlled trials that established the role of sunscreens in the prevention of actinic keratoses, squamous cell carcinomas, nevi, and melanomas. Sunscreens also prevent photoimmunosuppression and signs of photoaging. Continued efforts in public education on the proper application of sunscreens and the practice of photoprotection in general are needed.



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Title Page

Publication date: March 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 3, Supplement 1





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Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate

Publication date: Available online 10 February 2017
Source:Journal of the American Academy of Dermatology
Author(s): Joanna Przybyszewska, Abraham Zlotogorski, Yuval Ramot
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to cutaneous human beta-papillomavirus infections causing persistent flat warts or pityriasis versicolor–like lesions. This generalized verrucous skin disorder resembles generalized verrucosis, but these 2 conditions are distinguished by differences in clinical manifestation and the human papillomavirus types involved. A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 (EVER1) and TMC8 (EVER2) determine susceptibility to this disorder; however, they have not solved all EV cases fully. These deficiencies account for 75% of affected individuals, leaving a substantial number of patients without an underlying genetic cause. Recently, it has been revealed that mutations in additional genes (RHOH, MST-1, CORO1A, and IL-7) result in extensive human beta-papillomavirus replication and therefore manifest with an EV-like phenotype. The term "acquired EV" is used to describe an EV-like phenotype that develops in immunocompromised hosts, and the introduction of this entity further aggravates the confusion. Reevaluation of these entities is warranted. Here, we review the available data on this issue, provide up to date information on the major characteristics that differentiate between these seemingly clinically similar disorders, and highlight the different mechanisms involved in each disorder.



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Kinetics of plasma biomarkers of inflammation and lung injury in surgical patients with or without postoperative pulmonary complications.

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BACKGROUND: Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings. OBJECTIVE: To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP). DESIGN: A preplanned substudy of a randomised controlled trial. SETTING: Operation room of five centres. PATIENTS: Two hundred and forty-two adult patients scheduled for abdominal surgery at risk of developing PPCs. INTERVENTIONS: High (12 cmH2O) versus low (

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European Society of Anaesthesiology evidence-based and consensus-based guidelines on postoperative delirium.

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The purpose of this guideline is to present evidence-based and consensus-based recommendations for the prevention and treatment of postoperative delirium. The cornerstones of the guideline are the preoperative identification and handling of patients at risk, adequate intraoperative care, postoperative detection of delirium and management of delirious patients. The scope of this guideline is not to cover ICU delirium. Considering that many medical disciplines are involved in the treatment of surgical patients, a team-based approach should be implemented into daily practice. This guideline is aimed to promote knowledge and education in the preoperative, intraoperative and postoperative setting not only among anaesthesiologists but also among all other healthcare professionals involved in the care of surgical patients. (C) 2017 European Society of Anaesthesiology

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In vitro evaluation of ruthenium complexes for photodynamic therapy

Publication date: Available online 11 February 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Wenna Li, Qiang Xie, Linglin Lai, Zhentao Mo, Xiaofang Peng, Ennian Leng, Dandan Zhang, Hongxia Sun, Yiqi Li, Wenjie Mei, Shuying Gao
BackgroundPhotodynamic therapy (PDT) is a promising new anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDTs mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated.MethodsPhotocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization. Mitochondrial membrane potential (MMP), cell apoptosis, DNA fragmentation, c-Myc gene expression, and telomerase activities were also assayed.ResultsRup-03 and Rup-04 had the lowest IC50 values. Rup-03 had an IC50 value of 29.5±2.3μM in HepG2 cells and 59.0±6.1μM in RAW264.7 cells, while Rup-04 had an IC50 value of 40.0±3.8μM in SGC-7901 cells. The complexes also induced cellular morphological changes and impaired cellular ability to scavenge ROS, and accumulated preferentially in mitochondria and endoplasmic reticulum. Rup-03 reduced MMP levels, induced apoptosis, and repressed both c-Myc mRNA expression and telomerase activity in HepG2 cells.ConclusionsAmong six candidates, Rup-03-mediated PDT is most effective against HepG2 and RAW264.7, with a similar efficacy as that of Rup-04-mediated PDT against SGC-7901 cells. Repression of ROS scavenging activities and c-Myc expression, which mediated DNA damage-induced cell apoptosis and repression of telomerase activity, respectively, were found to be involved in the anticancer mechanisms of Rup-03.



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Photodynamic Therapy (PDT) for Adenoid Cystic Carcinoma of the Tracheo-Bronchial tree; Report of 4 cases

Publication date: Available online 11 February 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Keyvan Moghissi, Kate Dixon




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Competition assays revealed Paenibacillus pasadenensis strain R16 as a novel antifungal agent

Publication date: Available online 10 February 2017
Source:Microbiological Research
Author(s): Alessandro Passera, Giovanni Venturini, Giovanna Battelli, Paola Casati, Francesca Penaca, Fabio Quaglino, Piero Attilio Bianco
The development of new sustainable containment strategies of plant diseases is very important to guarantee food security while reducing the environmental impact of agriculture. Research of new biocontrol agents is a long and difficult process that involves several steps that start from the identification of possible candidates which, for example, show antibiotic activities, and ends with in field, large scale trials. In this study, the plant growth promoting potential and antifungal effect exerted by a novel, putative candidate biocontrol agent, strain R16, identified as Paenibacillus pasadenensis by sequence analysis of 16S rRNA and rpoB genes, against three important plant pathogenic fungi (Botrytis cinerea, Fusarium verticillioides, and Phomopsis viticola), were assessed. Biochemical assays to determine plant growth promoting potential gave negative results for siderophore production and phosphate solubilization, and positive results for ACC-deamination and IAA production. Further biochemical assays for endophytic lifestyle and antifungal activity gave positive results for catalase and chitinase activity, respectively. In vitro antagonism assays showed that strain R16 is effective against B. cinerea, reducing mycelial growth both in dual-culture and through volatile substances, characterized to be mostly composed by farnesol, and inhibiting conidia germination. Good antagonistic potential was also observed in vitro towards P. viticola, but not towards F. verticillioides. Moreover, in vivo assays confirmed the strain R16 activity reduced the infection rate on B. cinerea-inoculated berries. The obtained results firstly proved that P. pasadenesis strain R16 is a putative plant growth promoter and effective against phytopathogenic fungi. Further studies will be needed to investigate the possible application of this strain as a biocontrol agent.



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Colonization and beneficial effects on annual ryegrass by mixed inoculation with plant growth promoting bacteria

Publication date: Available online 10 February 2017
Source:Microbiological Research
Author(s): Nádia L. Castanheira, Ana Catarina Dourado, Isabel Pais, José Semedo, Paula Scotti-Campos, Nuno Borges, Gilda Carvalho, Maria Teresa Barreto Crespo, Paula Fareleira
Multi-strain inoculants have increased potential to accomplish a diversity of plant needs, mainly attributed to its multi-functionality. This work evaluated the ability of a mixture of three bacteria to colonize and induce a beneficial response on the pasture crop annual ryegrass. Pseudomonas G1Dc10 and Paenibacillus G3Ac9 were previously isolated from annual ryegrass and were selected for their ability to perform multiple functions related to plant growth promotion. Sphingomonas azotifigens DSMZ 18530T was included due to nitrogen fixing ability. The effects of the bacterial mixture were assessed in gnotobiotic plant inoculation assays and compared with single and dual inoculation treatments. Triple inoculation with 3×108 bacteria significantly increased plant dry weight and leaf pigments, indicating improved photosynthetic performance. Plant lipid biosynthesis was enhanced by 65%, mainly due to the rise of linolenic acid, an omega-3 fatty acid with high dietary value. Electrolyte leakage, an indicator of plant membrane stability under stress, was decreased pointing to a beneficial effect by inoculation. Plants physiological condition was more favoured by triple inoculation than by single, although benefits on biomass were only evident relative to non-inoculated plants. The colonization behaviour and coexistence in plant tissues were assessed using FISH and GFP-labelling, combined with confocal microscopy and a cultivation-based approach for quantification. The three strains occupied the same sites, localizing preferentially along root hairs and in stem epidermis. Endophytic colonization was observed as bacteria entered root and stem inner tissues. This study reveals the potential of this mixture of strains for biofertilization, contributing to improve crop productivity and nutritional value.

Graphical abstract

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Donkey's milk allergy

A 25 years-old woman, with a history of personal atopic dermatitis, allergic asthma and hay fever, experienced a facial angioedema 5 minutes after consuming fresh donkey's milk for the first time (Fig. 1). She developed dyspnea and collapsed after a few minutes. The patient required administration of adrenaline and corticosteroids. During her childhood, her atopic dermatitis was treated with different topical treatments including donkey's milk based emollients. She never presented reactions to this topical treatment and she had no history of food allergy.

This article is protected by copyright. All rights reserved.



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Data supporting the inability of indomethacin to induce autophagy in U251 glioma cells

Publication date: Available online 10 February 2017
Source:Data in Brief
Author(s): Aleksandar Pantovic, Katarina Arsikin, Milica Kosic, Biljana Ristic, Vladimir Trajkovic, Ljubica Harhaji-Trajkovic
Autophagy, a catabolic process involving intracellular degradation of unnecessary or dysfunctional cellular components through the lysosomal machinery, could act as a prosurvival, as well as a cytotoxic mechanism [1]. Cyclooxygenase inhibitor indomethacin inhibits proliferation of glioma cells, and has been reported to reduce the activity of the main autophagy repressor mammalian target of rapamycin (mTOR) [2]. Here we investigated the ability of indomethacin to induce autophagy in U251 human glioma cells. We assessed the influence of indomethacin on intracellular acidification, expression of proautophagic protein beclin-1, and conversion of microtubule-associated protein light chain 3-I (LC3-I) to autophagosome-associated LC3-II, in the presence or absence of lysosomal inhibitors. The effect of genetic and pharmacological downregulation of autophagy on the cytotoxicity of indomethacin was evaluated. The interpretation of these data can be found in "In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway" (Pantovic et al. 2017; doi:10.1016/j.biocel.2016.12.007) [2].



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A brief dataset on the model-based evaluation of the growth performance of Bacillus coagulans and L-lactic acid production in a lignin-supplemented medium

Publication date: Available online 11 February 2017
Source:Data in Brief
Author(s): Robert Glaser, Joachim Venus
The data presented in this article are related to the research article entitled "Model-based characterisation of growth performance and L-lactic acid production with high optical purity by thermophilic Bacillus coagulans in a lignin-supplemented mixed substrate medium (R. Glaser and J. Venus, 2016) [1]". This data survey provides the information on characterization of three Bacillus coagulans strains. Information on cofermentation of lignocellulose-related sugars in lignin-containing media is given. Basic characterization data are supported by optical-density high-throughput screening and parameter adjustment to logistic growth models. Lab scale fermentation procedures are examined by model adjustment of a Monod kinetics-based growth model. Lignin consumption is analysed using the data on decolorization of a lignin-supplemented minimal medium.



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Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions

Publication date: Available online 10 February 2017
Source:Data in Brief
Author(s): Eleni Kotsampasakou, Sylvia E. Escher, Gerhard F. Ecker
Hyperbilirubinemia is a pathological condition, very often indicative of underlying liver condition that is characterized by excessive accumulation of conjugated or unconjugated bilirubin in sinusoidal blood. In literature there are several indications associating the inhibition of the basolateral hepatic transporters Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and 1B3) with hyperbilirubinemia. In this article, we present a curated human hyperbilirubinemia dataset and the respective OATP1B1 and 1B3 inhibition predictions obtained from an effort to generate a classification model for hyperbilirubinemia. These data originate from the research article "Linking organic anion transporting polypeptide 1b1 and 1b3 (oatp1b1 and oatp1b3) interaction profiles to hepatotoxicity- the hyperbilirubinemia use case". [1] We further provide the full list of descriptors used for generating the hyperbilirubinemia classification models as well as the calculated descriptors for each compound of the dataset that was used to build the classification model.



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Knowledge, Attitude and Practices of Dentists Towards Oral Health Care During Pregnancy: A Cross-Sectional Survey in New South Wales, Australia

Abstract

Background

Studies internationally show a lack of consensus among dentists regarding perinatal oral health yet no studies in Australia has explored the perceptions of Dentists in this area. This study aims to determine the knowledge, perceptions and practices of dentists in New South Wales (NSW), Australia about perinatal oral health.

Method

An online survey was distributed to 1357 members of the Australian Dental Association (NSW) and 185 (13.4%) completed surveys were returned.

Results

Most dentists (99%) stated that pregnant women should receive a dental check, yet only 20% agreed that there was a good understanding among health professionals on this topic. Dentists were aware of safe dental practices during pregnancy but had limited knowledge about the association between periodontal disease and birth outcomes. Dentists were more likely to advise pregnant women to delay dental visits when there was a perceived lack of knowledge of the risks involved (OR 2.157) or were concerned about providing treatment without consent from their general practitioner (OR 2.449). Most dentists (95.7%) stated they wanted further information about dental care during pregnancy.

Conclusion

Findings suggest a need for continuing education for dentists and practice guidelines on perinatal oral health. Further research with a national sample is recommended to confirm these findings.

This article is protected by copyright. All rights reserved.



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Παρασκευή 10 Φεβρουαρίου 2017

1β,25-Dihydroxyvitamin D3: A new vitamin D metabolite in human serum

Publication date: Available online 11 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Steven Pauwels, Ivo Jans, Jaak Billen, Annemieke Heijboer, Annemieke Verstuyf, Geert Carmeliet, Chantal Mathieu, Miguel Maestro, Etienne Waelkens, Pieter Evenepoel, Roger Bouillon, Dirk Vanderschueren, Pieter Vermeersch
BackgroundThe measurement of 1α,25(OH)2D3 in human serum poses a true challenge as concentrations are very low and structurally similar metabolites can interfere.Materials and methodsDuring optimization of our in-house LC-MSMS method for serum 1α,25(OH)2D3 a previously co-eluting isobaric interference was separated. The isobar was identified as 1β,25(OH)2D3 by comparing retention time and fragmentation spectra to standards (other isobaric dihydroxylated vitamin D3 analogs). 1β,25(OH)2D3 showed specific cluster formation (water), not present in 1α,25(OH)2D3. 1β,25(OH)2D3 was measured in serum of apparently healthy human volunteers (n=20), patients with high serum 25-hydroxyvitamin D [25(OH)D] concentrations (>50ng/mL) (n=33 among which 4 with very high levels (>150ng/mL)) and patients with kidney failure (n=68; 39 stage 1–3, 29 stage 4–5). Pearson's r was calculated for correlations and Mann-Whitney statistic to compare group medians.ResultsMedian serum 1β,25(OH)2D3 was 11pg/mL in apparently healthy volunteers and increased to 20pg/mL for serum 25(OH)D concentrations above 80ng/mL (n=22) (p<0.0001). 1β,25(OH)2D3 concentrations were significantly correlated to serum 25(OH)D concentrations (r=0.85) for the combined results from healthy volunteers and patient sera (n=53) (p<0.0001). For patients with kidney failure, median serum 1β,25(OH)2D3 was 7pg/mL and not different from the median level in healthy volunteers (p=0.06). The median concentration did not vary with different stages.ConclusionsWe present evidence for the widespread presence of 1β,25(OH)2D3, a new vitamin D metabolite, in human serum. The level increases with rising serum 25(OH)D concentrations and is particularly high in patients with very high 25(OH)D levels. We previously demonstrated that 1β,25(OH)2D3 is a poor genomic agonist but a potent non-genomic antagonist of 1α,25(OH)2D3. The clinical implications of the presence of this analog therefore require further exploration.



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Pilot study to evaluate a plasma device for the treatment of onychomycosis

Summary

Onychomycosis is a fungal infection of the nail unit, and is the most common of the nail disorders. Current therapies for onychomycosis have less than ideal efficacy and have the potential for adverse effects. As previous studies have shown that nonthermal plasma inhibits the in vitro growth of Trichophyton rubrum, we conducted a pilot study on 19 participants with toenail onychomycosis. The primary endpoint was safety of the device, and secondary outcome measures were clinical efficacy and mycological cure. Patient satisfaction was measured using questionnaires at the completion of the study. All but one patient met the primary endpoint of safety and there were no long-term sequelae. The overall clinical cure was 53.8% and the mycological cure was 15.4%. The majority of patients were satisfied with the treatment. Our conclusions are that nonthermal plasma is a safe treatment and may have a beneficial effect on toenail onychomycosis.



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Fingolimod and melanoma risk: is there sufficient evidence?



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Screening for colorectal cancer

Publication date: Available online 10 February 2017
Source:Seminars in Oncology
Author(s): Youngjee Choi, Heather F. Sateia, Kimberly S. Peairs, Rosalyn W. Stewart
This review will comprise a general overview of the impact of colorectal cancer (CRC), as well as CRC risk factors, screening modalities, guideline recommendations for screening in average-risk and high-risk individuals, and our approach to CRC screening.



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Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST v1.1-defined disease progression in clinical trials

Publication date: Available online 10 February 2017
Source:Seminars in Oncology
Author(s): Dickran Kazandjian, Patricia Keegan, Daniel L Suzman, Richard Pazdur, Gideon M Blumenthal
ImportanceBased on anecdotal cases of clinically important decreases in tumor size following initial evidence of disease progression when treating patients with anti-PD-1 therapies, investigators have conducted clinical trials in patients with metastatic non-small lung cancer (mNSCLC) receiving anti-PD-1 therapy allowing for treatment past RECIST-defined disease progression (TPP). However, it remains unclear what the true benefit of TPP is.ObjectiveWe describe the findings of a pooled analysis of three clinical trials where treatment of patients with mNSCLC permitted TPP in terms of reduction in the sum of target lesions following initial RECIST-defined progression.DesignWe analyzed pooled data from three trials submitted to FDA evaluating anti-PD-1 therapy for the treatment of patients with mNSCLC in which patients were allowed to receive TPP. We identified patients who received TPP and the characteristics and post-TPP change in tumor burden. Results from this retrospective analysis are descriptively stated.ParticipantsAll patients had advanced or metastatic NSCLC and had previously received a platinum-based doublet regimen.ResultsIn total, 535 patients were treated with anti-PD-1 therapy in three clinical trials of which 121 patients (23%) received TPP. Among all 535 patients treated with anti-PD-1 therapy, the partial response (PR) rate (≥30% reduction in the size of target lesions compared to baseline) following TPP was 1.9% (10 of 535) or 8.3% (10 of 121) in the TPP subgroup. Patients who responded to TPP were more likely to have responded to the initial course of anti-PD-1 therapy, prior to progression.Conclusions and RelevanceOur evaluation indicated that 1.9% of anti-PD-1-treated patients with mNSCLC achieved a PR after receiving TPP. The subgroup of patients who received TPP appeared to have similar baseline characteristics and response to initial treatment compared to the overall population. This suggests that a treatment strategy that includes TPP may not benefit the overall population. The risks of TPP should be weighed against the low likelihood of a PR and the potential for changing to a different therapy with a higher likelihood of benefit.



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Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach

Publication date: Available online 11 February 2017
Source:Seminars in Oncology
Author(s): M. Boisdron-Celle, O. Capitain, R. Faroux, C. Borg, J.P. Metges, M.P. Galais, M. Kaassis, J. Bennouna, K. Bouhier-Leporrier, E. Francois, I. Baumgaertner, V. Guerin-Meyer, O. Cojocarasu, C. Roemer-Becuwe, C. Stampfli, L. Rosenfeld, T. Lecompte, V. Berger, A. Morel, E. Gamelin
Background5-FU-based treatments can lead to early-onset severe (4 to 5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pre-therapeutic screening for DPD deficiency using a multiparametric approach.MethodsTwo parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective non-randomized study. In Arm A, patients had DPD deficiency screening before treatment whereas in Arm B no pre-therapy screening was performed. Dosing was based on 5-FU administration guidelines of each institution. DPD deficiency screening was performed using a combined multiparametric approach (5-FUODPM Tox). The frequency of early grade 4-5 toxic events potentially induced by 5-FU was compared in the two groups.Results1142 patients (n=1116 evaluable) were enrolled. In Arm A, out of 718 evaluable patients, 9 grade 4 early toxicities potentially related to 5-FU were reported in 9 patients (1.2%) with no toxic death despite 1 complete DPD deficiency and 24 partial deficiencies. The 24 patients with partial deficiency had safe PK-monitored 5-FU. In Arm B, out of 398 evaluable patients, 17 grade 4-5 toxic early events potentially related to 5-FU were reported in 12 patients (4.2%). The incidence of early severe toxicity was significantly higher in Arm B, (p = 0.0019), confirming the positive impact of pre-therapeutic DPD assessment. The percent of patients with a toxicity grade 3 or higher observed in Arm A was 10.8% (n=78) compared to 17.55% (n=69) reported in Arm B (p=0.0497). The percentage of death was reduced from 2.5/1000 in Arm B to 0 in Arm A. The time to occurrence of all grade ≥3 toxicities was determined in both arms and the difference between the 2 arms was significant (P=0.047). Overall, one patient with complete DPD deficiency confirmed retrospectively died within 13 days from grade 5 multivisceral toxicity. Enrollment was prematurely closed after external experts' decision.ConclusionsMultiparametric pre-therapeutic DPD deficiency screening significantly lowered the risk of early severe toxicity and avoided an early toxic death. This approach should be used for safe administration of 5-FU-based treatments.



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Advances in understanding tumour evolution through single-cell sequencing

Publication date: Available online 11 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Jack Kuipers, Katharina Jahn, Niko Beerenwinkel
The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential.The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks.In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution.



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Synthesis and pharmacological evaluation of pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as potential GABAA-R ligands

Publication date: Available online 11 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Guerrini Gabriella, Giovanna Ciciani, Simona Daniele, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Claudia Martini, Silvia Selleri
The synthesis of a new series of 6-phenyl- and 6-benzylpyrazolo[1,5-a]pyrimidin-7(4H)-ones 2a-g and 3a-g, strictly related to derivatives with pyrazolobenzotriazine (PBT) and pyrazoloquinazoline (PQ) scaffold, was realized. The in vitro GABAA-receptor subtype affinity was evaluated and from preliminary pharmacological studies, compound 3g shows anxiolytic-like effect at 10-30 mg/kg.

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Construction of a library of structurally diverse ribonucleopeptides with catalytic groups

Publication date: Available online 10 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Tomoki Tamura, Shun Nakano, Eiji Nakata, Takashi Morii
Functional screening of structurally diverse libraries consisting of proteins or nucleic acids is an effective method to obtain receptors or aptamers with unique molecular recognition characteristics. However, further modification of these selected receptors to exert a newly desired function is still a challenging task. We have constructed a library of structurally diverse ribonucleopeptides (RNPs) that are modified with a catalytic group, in which the catalytic group aligns with various orientations against the ATP binding pocket of RNA subunit. As a proof-of-principle, the screening of the constructed RNP library for the catalytic reaction of ester hydrolysis was successfully carried out. The size of both the substrate-binding RNA library and the catalytic group modified peptide library are independently expandable, and thus, the size of RNPs library could be enlarged by a combination of these two subunits. We anticipate that the library of functionalized and structurally diverse RNPs would be expanded for various other catalytic reactions.

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Design, synthesis and preliminary biological evaluation of indole-3-carboxylic acid-based skeleton of Bcl-2/Mcl-1 dual inhibitors

Publication date: Available online 11 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Tingting Liu, Yichao Wan, Renshuai Liu, Lin Ma, Minyong Li, Hao Fang
The B-cell lymphoma-2 (Bcl-2) family proteins are attractive targets for cancer therapy. In our previous work, the structure-activity relationship of WL-276 was studied. According to the results, rhodanine derivatives show potent binding affinity for Bcl-2 and Mcl-1 protein and show weaker activity against Bcl-XL protein. Based on the previous results, a new class of indole-3-carboxylic acid-based derivatives were designed and synthesized as Bcl-2/Mcl-1 dual inhibitors. Among them, compound 17 has a Ki value of 0.26 μM for Bcl-2 protein and is better than WL-276. Further more, it inhibits the myeloid cell leukemia sequence 1 (Mcl-1) protein with a Ki value of 72 nM. Especially, compound 31 can selectively acting on Bcl-2 and Mcl-1 protein but not Bcl-XL protein, which has great significance for developing dual inhibitors targeting Bcl-2 and Mcl-1 protein, as well as specific antitumor abilities in cells.

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3-Phenylalkyl-2H-chromenes and -chromans as novel rhinovirus infection inhibitors

Publication date: Available online 10 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Cinzia Conti, Luca Proietti Monaco, Nicoletta Desideri
Following our studies on structure-activity relationships of anti-rhinovirus chromene and chroman derivatives, we designed and synthesized new series of 3-phenylalkyl-2H-chromenes and –chromans bearing differently sized, aliphatic linker chains between the two cycles. The cytotoxicity and the antiviral activity of the new compounds on human rhinovirus (HRV) serotype 1B and 14 infection were evaluated in HeLa cell cultures. Most of the tested compounds interfered with HRV1B multiplication in the micromolar or submicromolar concentrations while HRV14 was less susceptible. 3-[3-(4-Chlorophenyl)propyl]chroman (9c) was selected for preliminary mechanism of action studies due to its potent activity against both serotypes (IC50 of 0.48 μM and 1.36 μM towards HRV1B and 14, respectively) coupled with high selectivity (SI = 206.18 and 73.26, respectively). Results of time of addition/removal studies suggest that 9c, similarly to related derivatives, behaves as a capsid binder interfering with some early events of the HRV1B infectious cycle.

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A retrospective analysis of catheter-based sources in intravascular brachytherapy

Publication date: Available online 10 February 2017
Source:Brachytherapy
Author(s): J. DeCunha, C. Janicki, S.A. Enger
PurposeCoronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls.Methods and MaterialsA dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation.ResultsDose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions.ConclusionSOur findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.



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Intraoperative factors associated with stranded source placement accuracy in low–dose rate prostate brachytherapy

Publication date: Available online 10 February 2017
Source:Brachytherapy
Author(s): M.F. Jamaluddin, S. Ghosh, M.P. Waine, M. Tavakoli, J. Amanie, A.D. Murtha, D. Yee, N. Usmani
PurposeThe quality of a low–dose rate prostate brachytherapy implant depends on the accurate placement of sources in their planned locations. This study investigates intraoperative factors that potentially contribute to stranded source placement inaccuracy in prostate brachytherapy.Methods and MaterialsIntraoperative video images of the brachytherapist's hand motions and needle insertions during the implant procedure were acquired for analysis. Using video analysis software, maximum and average needle insertion velocities were determined. The number of needle insertion attempts and the use of the brachytherapist's other hand to manipulate the needle direction were also recorded. Sources misplacements were analyzed using an ultrasound-based method described elsewhere.ResultsFifteen patients agreed to undergo this study; 1619 125I seeds were inserted using 357 needles; 1197 seeds were confidently identified using ultrasound images and included in the analysis. The mean overall misplacement was 0.49 cm (0–2 cm, 95% CI = 0.47–0.51); 614 seeds were delivered with a single pass and 583 seeds with >1 passes (range 2–6). The mean maximum needle velocity was 12.34 cm s−1 (range 4–28 cm s−1) and mean average velocity was 4.76 cm s−1 (range 0.4–17.4 cm s−1); 747 seeds were delivered with manipulation of the needle. The generalized linear model test was used to analyze factors contributing to seed misplacement, and it was found that a maximum speed <12 cm s−1 was associated with a decrease in seed misplacement by 0.049 cm vs. a maximum speed >12 cm s−1, p = 0.0121). Other evaluated factors were found to have no statistically significant correlation with seed misplacement: average speed (p = 0.4947), manual manipulation of needle (p = 0.9264), and number of needle passes (p = 0.8907).ConclusionsThis study identified that needles inserted with lower maximum velocity were associated with less seed misplacement. Manual manipulation of the needle, number of passes, and average speed did not show statistically significant correlation with seed misplacement.



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GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory T-cell responses that inhibit tumor growth

Publication date: Available online 10 February 2017
Source:Vaccine
Author(s): Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8+ T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8+ T-cell responses to both vaccine antigens. Intradermal vaccination of C57BL/6 mice with GTL001 adjuvanted with a TLR3 agonist (polyinosinic-polycytidylic acid) or a TLR7 agonist (topical 5% imiquimod cream) induced strong HPV16 E7-specific T-cell responses capable of eradicating HPV16 E7-expressing tumors. Tumor-free mice also had antigen-specific memory T-cell responses that protected them against a subsequent challenge with HPV18 E7-expressing tumor cells. In addition, vaccination with bivalent vaccines containing CyaA-HPV16 E7 and CyaA fused to a tumor-associated antigen (melanoma-specific antigen A3, MAGEA3) or to a non-viral, non-tumor antigen (ovalbumin) eradicated HPV16 E7-expressing tumors and protected against a later challenge with MAGEA3- and ovalbumin-expressing tumor cells, respectively. These results show that CyaA-based bivalent vaccines such as GTL001 can induce both therapeutic and prophylactic anti-tumor T-cell responses. The CyaA platform can be adapted to different antigens and adjuvants, and therefore may be useful for developing other therapeutic vaccines.



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Influenza vaccination in healthcare workers; comparison of side effects and preferred route of administration of intradermal versus intramuscular administration

Publication date: Available online 10 February 2017
Source:Vaccine
Author(s): W.J. Meijer, A.M.J. Wensing, A.A. Bos, J.C.F. Kuiphuis, E.M.M. Hagelen, J.C. Wilschut, M.J.T. de Vries, A. Riezebos-Brilman
ObjectiveTo explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers.DesignProspective cohort study.SettingTwo University Medical Centers in The Netherlands.ParticipantsHealthcare workers receiving an influenza vaccination.MethodsHealthcare workers that were vaccinated during the influenza vaccination season of 2012–2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination.ResultsSide effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, p<0.001). Local side effects were perceived as more severe in healthcare workers receiving the intradermal vaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated.ConclusionsThis study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine.



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Bactericidal activity of sera from adolescents vaccinated with bivalent rLP2086 against meningococcal serogroup B outbreak strains from France

Publication date: Available online 10 February 2017
Source:Vaccine
Author(s): Muhamed-Kheir Taha, Julio Cesar Hawkins, Paul Liberator, Ala-Eddine Deghmane, Lubomira Andrew, Li Hao, Thomas R. Jones, Lisa K. McNeil, Robert E. O'Neill, John L. Perez, Kathrin U. Jansen, Annaliesa S. Anderson
ObjectivesBivalent rLP2086 (Trumenba®; MenB-FHbp), composed of two factor H binding proteins (FHbps), is a vaccine approved in the United States for prevention of Neisseria meningitidis serogroup B (MnB) invasive meningococcal disease (IMD). Bactericidal activity of sera from subjects vaccinated with bivalent rLP2086 was assessed against MnB isolates from recent disease outbreaks in France.MethodsMnB isolates from IMD cases were characterized by whole genome sequencing and FHbp expression was assessed using a flow cytometry-based assay. Sera from subjects (11–<19years old) vaccinated with bivalent rLP2086 at 0, 2, and 6months were evaluated. Bactericidal activity was measured in serum bactericidal assays using human complement (hSBAs). The response rate (RR) represents the percentage of subjects with an hSBA titer ⩾1:4.ResultsThe six MnB outbreak isolates expressed diverse FHbp variants: A22, B03, B24 (two isolates), B44, and B228. FHbp expression levels ranged from 1309 to 8305 (mean fluorescence intensity units). The RR of preimmune sera from subjects was 7% to 27%. RRs increased for all isolates after each vaccine dose. After two doses, RRs ranged from 40% to 93%. After dose 3, RRs were ⩾73% for all isolates (range, 73%–100%).ConclusionsEach of the representative French outbreak isolates was killed by sera from subjects vaccinated with bivalent rLP2086. Vaccination elicited an immune response with bactericidal activity against these diverse isolates in a large proportion of subjects at risk. These results provide additional support for the licensure strategy of testing MnB strains expressing vaccine-heterologous FHbp variants in hSBAs and further illustrate the breadth of efficacy of this protein-based MnB vaccine.



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PCV13 serotype decrease in Italian adolescents and adults in the post-PCV13 era: Herd protection from children or secular trend?

Publication date: Available online 10 February 2017
Source:Vaccine
Author(s): Francesco Nieddu, Maria Moriondo, Elisa De Vitis, Silvia Ricci, Giuseppe Indolfi, Massimo Resti, Caterina Vocale, Maria Paola Landini, Assunta Sartor, Chiara Azzari
Background and aim of the workIn 2010 PCV13 replaced PCV7 in the pediatric vaccination schedule for Italian children. While a strong herd effect was demonstrated for PCV7, a possible herd effect due to PCV13 is still under debate. Our aim was to evaluate differences in the distribution of pneumococcal serotypes between the pre and post-PCV13 eras in unvaccinated Italian adolescents and adults with laboratory-confirmed pneumococcal infection from 3 Italian Regions with a high rate of PCV13 vaccination of children.Patients and methodsAdolescents and adults admitted with laboratory-confirmed pneumococcal infection in the hospitals of 3 Italian Regions (Friuli-Venezia Giulia, Emilia Romagna, and Tuscany) between April 2006 and June 2016 were included in the study. Diagnosis of pneumococcal infection and serotyping were performed with Real Time PCR directly on normally sterile fluids or on culture isolates.Results523 patients with laboratory-confirmed pneumococcal infection were enrolled (Male/Female ratio was 300/223, 1.3; median age 67.1, IQR 53.4–74.9). None of the patients had been vaccinated with any pneumococcal vaccine; 96.4% were serotyped. Overall, the most frequent serotypes were 3 (67/504, 13.3%), 8 (43/504, 8.5%), and 19A (38/504, 7.5%). Serotype distribution differed among age classes and clinical presentations.Overall, PCV13 serotypes accounted for 47.6% of cases: 62.3% in the pre-PCV13 era and 45.0% in the post-PCV13 era; (p=0.005 OR=2.03; CL 95%: 1.2–3.3). Serotype 7F accounted for 12/77 (15.6%) of all serotypes in the pre-PCV13 period and for 12/427 (2.8%) in the post-PCV13 period and was the only serotype significantly contributing to the difference in percentage between pre and post-PCV13 eras.ConclusionOur study demonstrated a difference in percentage in serotype distribution in adolescents and adults laboratory-confirmed pneumococcal infection between the pre and post-PCV13 eras. This difference is mainly due to the decrease of serotype 7F. Thus, in order to decrease disease burden, adults and in particular the elderly should be offered a specific vaccination program.



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Vacuum-assisted decellularization: an accelerated protocol to generate tissue-engineered human tracheal scaffolds

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Colin R. Butler, Robert E. Hynds, Claire Crowley, Kate H.C. Gowers, Leanne Partington, Nicholas J. Hamilton, Carla Carvalho, Manuela Platé, Edward R. Samuel, Alan J. Burns, Luca Urbani, Martin A. Birchall, Mark W. Lowdell, Paolo De Coppi, Sam M. Janes
Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a tracheal replacement but there is no present consensus of how this may be achieved. Tissue engineering using decellularized or synthetic tracheal scaffolds offers a new avenue for airway reconstruction. Decellularized human donor tracheal scaffolds have been applied in compassionate-use clinical cases but naturally derived extracellular matrix (ECM) scaffolds demand lengthy preparation times. Here, we compare a clinically applied detergent-enzymatic method (DEM) with an accelerated vacuum-assisted decellularization (VAD) protocol. We examined the histological appearance, DNA content and extracellular matrix composition of human donor tracheae decellularized using these techniques. Further, we performed scanning electron microscopy (SEM) and biomechanical testing to analyze decellularization performance. To assess the biocompatibility of scaffolds generated using VAD, we seeded scaffolds with primary human airway epithelial cells in vitro and performed in vivo chick chorioallantoic membrane (CAM) and subcutaneous implantation assays. Both DEM and VAD protocols produced well-decellularized tracheal scaffolds with no adverse mechanical effects and scaffolds retained the capacity for in vitro and in vivo cellular integration. We conclude that the substantial reduction in time required to produce scaffolds using VAD compared to DEM (approximately 9 days vs. 3–8 weeks) does not compromise the quality of human tracheal scaffold generated. These findings might inform clinical decellularization techniques as VAD offers accelerated scaffold production and reduces the associated costs.



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Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Wei Zhu, Xin Qu, Jie Zhu, Xuanyi Ma, Sherrina Patel, Justin Liu, Pengrui Wang, Cheuk Sun Edwin Lai, Maling Gou, Yang Xu, Kang Zhang, Shaochen Chen
Living tissues rely heavily on vascular networks to transport nutrients, oxygen and metabolic waste. However, there still remains a need for a simple and efficient approach to engineer vascularized tissues. Here, we created prevascularized tissues with complex three-dimensional (3D) microarchitectures using a rapid bioprinting method – microscale continuous optical bioprinting (μCOB). Multiple cell types mimicking the native vascular cell composition were encapsulated directly into hydrogels with precisely controlled distribution without the need of sacrificial materials or perfusion. With regionally controlled biomaterial properties the endothelial cells formed lumen-like structures spontaneously in vitro. In vivo implantation demonstrated the survival and progressive formation of the endothelial network in the prevascularized tissue. Anastomosis between the bioprinted endothelial network and host circulation was observed with functional blood vessels featuring red blood cells. With the superior bioprinting speed, flexibility and scalability, this new prevascularization approach can be broadly applicable to the engineering and translation of various functional tissues.



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A new approach to analyze data from EEG-based concealed face recognition system

Publication date: Available online 10 February 2017
Source:International Journal of Psychophysiology
Author(s): A.H. Mehrnam, A.M. Nasrabadi, M. Ghodoosi, A. Mohammadian, Sh. Torabi
The purpose of this study is to extend a feature set with non-linear features to improve classification rate of guilty and innocent subjects. Non-linear features can provide extra information about phase space. The Event-Related Potential (ERP) signals were recorded from 49 subjects who participated in concealed face recognition test. For feature extraction, at first, several morphological characteristics, frequency bands, and wavelet coefficients (we call them basic-features) are extracted from each single-trial ERP. Recurrence Quantification Analysis (RQA) measures are then computed as non-linear features from each single-trial. We apply Genetic Algorithm (GA) to select the best feature set and this feature set is used for classification of data using Linear Discriminant Analysis (LDA) classifier. Next, we use a new approach to improve classification results based on introducing an adaptive-threshold. Results indicate that our method is able to correctly detect 91.83% of subjects (45 correct detection of 49 subjects) using combination of basic and non-linear features, that is higher than 87.75% for basic and 79.59% for non-linear features. This shows that combination of non-linear and basic- features could improve classification rate.



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Maternal morbidity and mortality in ElShatby and Dar Ismail maternity hospitals in Alexandria: A comparative study

Publication date: Available online 10 February 2017
Source:Alexandria Journal of Medicine
Author(s): Sahar khashab, Nermeen S. El Beltagy, Dina Badie
ObjectiveTo compare ElShatby University Maternity Hospital and Dar Ismail Public Hospital in regard to antenatal, natal, and postnatal morbidity and the causes of maternal mortality.MethodsA cross-sectional survey was conducted to study females who gave birth in each of the hospitals. Then, a prospective survey of the women was conducted until the 42nd day after delivery. Data were gathered from women who delivered in addition to their caring obstetricians as well as reviewing their medical records. Additionally, records of maternal mortality were reviewed. All females who gave birth between January and April 2014 (3months) were included in the study.ResultsTwo hundred and eighty females participated in the study (130 from ElShatby University Maternity Hospital and 150 from Dar Ismail Public Hospital). Significantly more rural women (29.2%) gave birth at ElShatby University Hospital than at Dar Ismail Public Hospital (16.7%), p=0.012. More than half of all the study participants (51.8%) suffered from anemia during pregnancy. A minority (5%) of the women were diagnosed with preeclampsia, all of whom gave birth at ElShatby Hospital. Caesarean section rate was significantly higher among women delivered at ElShatby University Hospital compared to Dar Ismail Hospital (61.5% versus 41.3%, p<001). Only 8.2% of all women needed ICU admission at ElShatby Hospital. The most common cause of maternal mortality was eclampsia, which accounted for 75% of deceased women.ConclusionFuture studies are needed to identify and understand better the avoidable factors contributing to the relatively high rates of maternal morbidity and mortality in public hospitals. Such information will be of significant use in the processes related to providing quality services, ensuring accessibility of those services, and allocating corresponding resources aimed at reducing maternal morbidity and mortality.



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Are Portrait Artists Superior Face Recognizers? Limited Impact of Adult Experience on Face Recognition Ability.

Author: Tree, Jeremy J.; Horry, Ruth; Riley, Howard; Wilmer, Jeremy B.
DOI: 10.1037/xhp0000328
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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Evolving the Keys to Visual Crowding.

Author: Van der Burg, Erik; Olivers, Christian N. L.; Cass, John
DOI: 10.1037/xhp0000337
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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The First Letter Position Effect in Visual Word Recognition: The Role of Spatial Attention.

Author: Aschenbrenner, Andrew J.; Balota, David A.; Weigand, Alexandra J.; Scaltritti, Michele; Besner, Derek
DOI: 10.1037/xhp0000342
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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It Does Exist! A Left-to-Right Spatial-Numerical Association of Response Codes (SNARC) Effect Among Native Hebrew Speakers.

Author: Zohar-Shai, Bar; Tzelgov, Joseph; Karni, Avi; Rubinsten, Orly
DOI: 10.1037/xhp0000336
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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Multisensory Cue Combination After Sensory Loss: Audio-Visual Localization in Patients With Progressive Retinal Disease.

Author: Garcia, Sara E.; Jones, Pete R.; Reeve, Eleanor I.; Michaelides, Michel; Rubin, Gary S.; Nardini, Marko
DOI: 10.1037/xhp0000344
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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Haptic Search for Movable Parts.

Author: Plaisier, Myrthe A.; Overvliet, Krista E.
DOI: 10.1037/xhp0000345
Publication Date: POST AUTHOR CORRECTIONS, 9 February 2017


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Sex differences in the development of prolactinoma in mice overexpressing hCG{beta}: role of TGF{beta}1

Female transgenic mice that overexpress the human chorionic gonadotrophin β subunit (hCGβ+) develop prolactinomas, whereas hCGβ+ males do not. The high levels of circulating hCG induce massive luteinization in the ovary of hCGβ+ females, and progesterone becomes the primary steroid hormone produced, but estradiol remains at physiological level. The involvement of high levels of progesterone in lactotroph proliferation is not clearly understood; hence, the pathogenesis of prolactinomas in hCGβ+ females remains unclear. TGFβ1 is an inhibitor of lactotroph function, and the reduced TGFβ1 activity found in prolactinomas has been proposed to be involved in tumor development. The aim of the present work was to study the role of TGFβ1 in the gender-specific development of prolactinomas in hCGβ+ mice. We compared the expression of different components of the pituitary TGFβ1 system in males and females in this model. We found reduced TGFβ1 levels, reduced expression of TGFβ1 target genes, TGFβ1 receptors, Ltbp1, Smad4 and Smad7 in hCGβ+ female pituitaries. However, no differences were found between the transgenic and wild-type male pituitaries. We postulate that decreased pituitary TGFβ1 activity in hCGβ+ females is involved in the development of prolactinomas. In fact, we demonstrated that an in vivo treatment carried out for increasing pituitary TGFβ1 activity, was successful in reducing the prolactinoma development, and the hyperprolactinemia in hCGβ+ females. Moreover, the stronger TGFβ1 system found in males could protect them from excessive lactotroph proliferation. Sex differences in the regulation of the pituitary TGFβ1 system could explain gender differences in the incidence of prolactinoma.



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Angiotensin II induces differential insulin action in rat skeletal muscle

Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague–Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P < 0.05) than that in the SHAM group and was associated with increased insulin-stimulated IRS-1 Ser307 and decreased Akt Ser473 and AS160 Thr642 phosphorylation and GLUT-4 expression. However, ANGII-500 infusion did not induce skeletal muscle insulin resistance or impair insulin signaling elements as initially anticipated. Moreover, we found that insulin-stimulated glucose uptake in the ANGII-500 group was accompanied by the enhanced expression of ACE2 and MasR proteins, which are the key elements in the non-classical pathway of the renin–angiotensin system. Collectively, this study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels.



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Editorial Advisory Board

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3





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Contents

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3





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Totally Implantable Wireless Ultrasonic Doppler Blood Flowmeters: Toward Accurate Miniaturized Chronic Monitors

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Michael A. Rothfuss, Jignesh V. Unadkat, Michael L. Gimbel, Marlin H. Mickle, Ervin Sejdić
Totally implantable wireless ultrasonic blood flowmeters provide direct-access chronic vessel monitoring in hard-to-reach places without using wired bedside monitors or imaging equipment. Although wireless implantable Doppler devices are accurate for most applications, device size and implant lifetime remain vastly underdeveloped. We review past and current approaches to miniaturization and implant lifetime extension for wireless implantable Doppler devices and propose approaches to reduce device size and maximize implant lifetime for the next generation of devices. Additionally, we review current and past approaches to accurate blood flow measurements. This review points toward relying on increased levels of monolithic customization and integration to reduce size. Meanwhile, recommendations to maximize implant lifetime should include alternative sources of power, such as transcutaneous wireless power, that stand to extend lifetime indefinitely. Coupling together the results will pave the way for ultra-miniaturized totally implantable wireless blood flow monitors for truly chronic implantation.



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Masthead

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3





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Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Invasive Breast Cancer: A Novel Technique to Obtain Histopathologic Information of Microvessel Density

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Naoko Mori, Shunji Mugikura, Shoki Takahashi, Koichi Ito, Chiaki Takasawa, Li Li, Minoru Miyashita, Atsuko Kasajima, Yu Mori, Takanori Ishida, Tetsuya Kodama, Kei Takase
We examined whether enhancement area ratios obtained by the new bubble detection method correlate with histologic microvessel density in invasive breast cancer. Forty consecutive patients with invasive breast cancer lesions underwent contrast-enhanced ultrasound. The ratio of enhanced area to manually segmented tumor area (enhancement area ratio) was obtained with the new method at peak and delayed phases (50–54, 55–59, 60–64 and 65–69 s). We also analyzed time–intensity curves to obtain peak intensity and area under curve. Enhancement area ratios in both peak and delayed phases (50–54, 55–59, 60–64 and 65–69 s) were significantly correlated with microvessel density (r = 0.57, 0.62, 0.68, 0.61 and 0.58; p = 0.0001, <0.0001, <.0001, <.0001 and 0.0001, respectively). In time–intensity curve analysis, peak intensity was significantly correlated (r = 0.43, p = 0.0073), whereas area under the curve was not (r = 0.29, p = 0.0769). Enhancement area ratios obtained by the new method were correlated with microvessel density in invasive breast cancer.



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A Novel Approach to Detecting Postpartum Hemorrhage Using Contrast-Enhanced Ultrasound

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Kenji Imai, Tomomi Kotani, Hiroyuki Tsuda, Tomoko Nakano, Akihiro Hirakawa, Fumitaka Kikkawa
The aim of this study was to estimate the efficacy of contrast-enhanced ultrasound (CEUS) in detecting postpartum hemorrhage (PPH) after cesarean section. This is the first study of CEUS in obstetric hemorrhage. A total of 37 patients, operated at Nagoya University Hospital, underwent CEUS. We evaluated the findings of CEUS, which were qualitatively defined as positive when pooling or leakage of contrast agent was observed in the uterine cavity, by measuring the amount of bleeding during the first 4 h after cesarean section. The time–intensity curve patterns of leaked contrast agents were also analyzed for quantitative prediction of the amount of blood loss. Significant differences between the excessive hemorrhage (N = 7) and non-excessive hemorrhage groups (N = 30) were noted in the occurrence of positive CEUS (p = 0.011). Additionally, mean postpartum blood loss markedly increased in patients with a positive CEUS (p = 0.002). From a quantitative perspective, the time until leakage of contrast agents was detected correlated with the amount of bleeding, but the other characteristics of the time–intensity curve pattern did not provide valuable information. In conclusion, CEUS, which enables bedside assessment and rapid diagnosis, is a promising strategy for the detection of PPH.



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Contrast-Enhanced Ultrasound Using Perfluorobutane-Containing Microbubbles in the Assessment of Liver Allograft Damage: An Exploratory Prospective Study

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Ijin Joo, Jae Young Lee, Dong Ho Lee, Ju Hyeon Jeon, Hyeyoung Kim, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh
This prospective study investigated the usefulness of contrast (perfluorobutane-containing microbubbles)-enhanced ultrasound in the non-invasive assessment of liver allograft damage. Forty-one liver recipients underwent contrast-enhanced ultrasound followed by a liver biopsy. The hepatic filling rate (time between the arrival of contrast agent in the right hepatic artery and the maximum intensity of hepatic parenchyma) and parenchymal intensity difference before and after instantaneous high-power emission in the Kupffer phase were measured. Patients with allograft damage had higher hepatic filling rates and lower parenchymal intensity differences than those without damage (42.0 ± 16.9 vs. 30.5 ± 7.7 s, p = 0.005; 6.1 ± 7.4 vs. 16.6 ± 16.1 dB, p = 0.047, respectively). In the diagnosis of liver allograft damage, hepatic filling rate and parenchymal intensity difference had sensitivities of 61.5% and 90.9% and specificities of 92.6% and 63.6% using cutoffs of >38.5 s and ≤10.3 dB, respectively. In conclusion, contrast-enhanced ultrasound may be a promising tool in the detection of liver allograft damage.



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Strain-Initialized Robust Bone Surface Detection in 3-D Ultrasound

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Mohammad Arafat Hussain, Antony J. Hodgson, Rafeef Abugharbieh
Three-dimensional ultrasound has been increasingly considered as a safe radiation-free alternative to radiation-based fluoroscopic imaging for surgical guidance during computer-assisted orthopedic interventions, but because ultrasound images contain significant artifacts, it is challenging to automatically extract bone surfaces from these images. We propose an effective way to extract 3-D bone surfaces using a surface growing approach that is seeded from 2-D bone contours. The initial 2-D bone contours are estimated from a combination of ultrasound strain images and envelope power images. Novel features of the proposed method include: (i) improvement of a previously reported 2-D strain imaging-based bone segmentation method by incorporation of a depth-dependent cumulative power of the envelope into the elastographic data; (ii) incorporation of an echo decorrelation measure-based weight to fuse the strain and envelope maps; (iii) use of local statistics of the bone surface candidate points to detect the presence of any bone discontinuity; and (iv) an extension of our 2-D bone contour into a 3-D bone surface by use of an effective surface growing approach. Our new method produced average improvements in the mean absolute error of 18% and 23%, respectively, on 2-D and 3-D experimental phantom data, compared with those of two state-of-the-art bone segmentation methods. Validation on 2-D and 3-D clinical in vivo data also reveals, respectively, an average improvement in the mean absolute fitting error of 55% and an 18-fold improvement in the computation time.



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Diagnosis of Complex Pulley Ruptures Using Ultrasound in Cadaver Models

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Isabelle Schöffl, Arnica Hugel, Volker Schöffl, Wolfgang Rascher, Jörg Jüngert
Pulley ruptures are common in climbing athletes. The purposes of this study were to determine the specific positioning of each pulley with regards to the joint, and to evaluate the ultrasound diagnostics of various pulley rupture combinations. For this, 34 cadaver fingers were analyzed via ultrasound, the results of which were compared to anatomic measurements. Different pulley ruptures were then simulated and evaluated using ultrasound in standardized dynamic forced flexion. Visualization of the A2 and A4 pulleys was achieved 100% of the time, while the A3 pulley was visible in 74% of cases. Similarly, injuries to the A2 and A4 pulleys were readily observable, while A3 pulley injuries were more challenging to identify (sensitivity of 0.2 for singular A3 pulley, 0.5 for A2/A4 pulley and 0.33 for A3/A4 pulley ruptures). Receiver operating characteristic analysis was used to evaluate the optimal tendon-bone distance for pulley rupture diagnosis, a threshold which was determined to be 1.9 mm for A2 pulley ruptures and 1.85 for A4 pulley ruptures. This study was the first to carry out a cadaver ultrasound examination of a wide variety of pulley ruptures. Ultrasound is a highly accurate tool for visualizing the A2 and A4 pulleys in a cadaver model. This method of pathology diagnosis was determined to be suitable for injuries to the A2 and A4 pulleys, but inadequate for A3 pulley injuries.



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High-Resolution Elastography for Thin-Layer Mechanical Characterization: Toward Skin Investigation

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Caroline Chartier, Yassine Mofid, Cécile Bastard, Véronique Miette, Annabel Maruani, Laurent Machet, Frédéric Ossant
Interest in elasticity estimation for thin layers is increasing because of the various potential applications, including dermatology and cosmetology. In this context, we propose a dedicated elastographic system using 1-D high-frequency transient elastography (HF-TE) to estimate the 1-D Young's modulus through the dermis and hypodermis, which are the two human skin layers of interest in this study. An experimental validation of the HF-TE method was first carried out on two homogeneous tissue-mimicking hard and soft phantoms. The Young's modulus values obtained in these phantoms were compared with those obtained by two complementary shear wave propagation techniques: shear wave-induced resonance elastography (SWIRE) and supersonic shear imaging (SSI). A third two-layer thin phantom, with mechanical properties similar to those of skin, was used to validate the ability of HF-TE to distinguish layers and measure elasticity. Finally, preliminary in vivo experiments conducted on forearm and cheek skin revealed the promising performance of HF-TE in measuring elasticity in the dermis and hypodermis.



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Acoustic Impedance Analysis with High-Frequency Ultrasound for Identification of Fatty Acid Species in the Liver

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Kazuyo Ito, Kenji Yoshida, Hitoshi Maruyama, Jonathan Mamou, Tadashi Yamaguchi
Acoustic properties of free fatty acids present in the liver were studied as a possible basis for non-invasive ultrasonic diagnosis of non-alcoholic steatohepatitis. Acoustic impedance was measured for the following types of tissue samples: Four pathologic types of mouse liver, five kinds of FFAs in solvent and five kinds of FFAs in cultured Huh-7 cells. A transducer with an 80-MHz center frequency was incorporated into a scanning acoustic microscopy system. Acoustic impedance was calculated from the amplitude of the signal reflected from the specimen surface. The Kruskal–Wallis test revealed statistically significant differences (p < 0.01) in acoustic impedance not only among pathologic types, but also among the FFAs in solvent and in cultured Huh-7 cells. These results suggest that each of the FFAs, especially palmitate, oleate and palmitoleate acid, can be distinguished from each other, regardless of whether they were in solution or absorbed by cells.



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Comparison of Two Inexpensive Rapid Prototyping Methods for Manufacturing Filament Target Ultrasound Phantoms

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3
Author(s): Krisztián Füzesi, Miklós Gyöngy
Current use of 3-D printers to manufacture ultrasound phantoms is limited to relatively expensive photopolymer jetting printers. The present work investigates the feasibility of using two common and inexpensive 3-D printer technologies, fused deposition modeling (FDM) and digital light processing (DLP), to print custom filament target phantoms. Acoustic characteristics obtained from printed solid blocks indicated that the printing materials—acrylonitrile butadiene styrene and polylactic acid for FDM and a photopolymer for DLP printing—were appropriate for use as scatterers. A regular grid of filaments was printed to study printing accuracy. As a proof of concept of the phantom manufacturing process, a complex pattern of filament targets was placed in de-ionized water to create a phantom, which was then imaged using an ultrasound imager. The pattern was clearly identifiable, although multiple reflections were observed, which underscores the importance of future work to enhance printing resolution. This goal is deemed possible using improvement of the DLP printing setup.



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Calendar

Publication date: March 2017
Source:Ultrasound in Medicine & Biology, Volume 43, Issue 3





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Effect of Low-Intensity Cavitation on the Isolated Human Thoracic Artery in Vitro

Publication date: Available online 10 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Algimantas Bubulis, Vida Garalienė, Vytautas Jurėnas, Jonas Navickas, Saulius Giedraitis
Reported here are the results of an experimental study on the response to low-intensity cavitation induced by low-frequency (4–6 W/cm2, 20 kHz and 32.6 kHz) ultrasound of isolated human arterial samples taken during conventional myocardial revascularization operations. Studies have found that low-frequency ultrasound results in a significant (48%–54%) increase in isometric contraction force and does not depend on the number of exposures (10 or 20) or the time passed since the start of ultrasound (0, 10 and 20 min), but does depend on the frequency and location (internal or external) of the blood vessels for the application of ultrasound. Diltiazem (an inhibitor of slow calcium channels) and carbachol (an agonist of muscarinic receptors) used in a concentration-dependent manner did not modify the relaxation dynamics of smooth muscle affected by ultrasound. Thus, ultrasound conditioned to the augmentation of the isometric contraction force the smooth muscle of blood vessels and did not improve endothelial- and calcium channel blocker-dependent relaxation.



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Fluorinated oligo(ethylene glycol) methacrylate-based copolymers: Tuning of self assembly properties and relationship with rheological behavior

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Federica Zuppardi, Francesco Raffaele Chiacchio, Roberta Sammarco, Mario Malinconico, Giovanna Gomez d'Ayala, Pierfrancesco Cerruti
A series of thermo-responsive oligo(ethylene glycol) methacrylate (OEGMA, Mn = 300 g/mol)-pentafluorostyrene (PFS) copolymers was prepared, and the effect of composition on polymer conformation changes and size of the self-assembled particles in solution was studied. Furthermore, the relationship between self-aggregation mechanistic steps in water and rheological properties is reported. Water-soluble OEGMA-PFS copolymers were synthesized at different molar ratios via free radical polymerization, and their phase transition behavior was investigated in detail by dynamic light scattering (DLS), 1H NMR, simultaneous rheometry-FTIR spectroscopy, and transmission electronic microscopy (TEM). All copolymers exhibited sharp and reversible LCST in water. LCST and particle size of the self-assemblying copolymers can be precisely tuned by varying monomer molar ratio. Simultaneous rheometry-FTIR spectroscopy showed that above the LCST, copolymers with higher OEGMA content form micron-sized and hydrated particles, resulting in a pseudo-hydrogel structure. When the hydrophobic character increases, a more significant dehydration of OEGMA side chains leads to a strengthening of polymer chain interactions, resulting in the formation of nanosized and phase-segregated particles. These results are also relevant with a view of using these structures as a template for the preparation of chemically or physically stabilized nanoparticles to be employed for a variety of applications, such as immobilization, controlled release and flocculation in water treatment.

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Isoindigo dye incorporated copolymers with diselenophenylethene: Synthesis, characterization, and enhanced mobilities in field-effect transistors with electrodes modified by thiol-based self-assembled monolayers

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): Keli Shi, Weifeng Zhang, Xiaotong Liu, Ye Zou, Gui Yu
In this study, we report the design and synthesis of two donor−acceptor isoindigo dye-based copolymers, namely PIIVS1 and PIIVS2, in which π−extended diselenophenylethene building block acts as electron-donating units. The charge transport properties of both copolymers were studied by fabricating field-effect transistors (FETs). The two copolymers-based FETs with electrodes modified by thiol self-assembled monolayers (SAMs) showed enhanced mobilities of up to 1.58 cm2 V−1 s−1 (average: 1.28 cm2 V−1 s−1), almost two times higher than those achieved in unmodified counterparts. Thereby, a systematical investigation on PIIVS2-based PFETs was performed, indicating contact resistances, contact angles and Au work function all changed in different extents, and more uniform thin film morphologies obtained in thiol-treated PFET devices. The results demonstrate the potential and feasibility of electrodes modification by thiol-based SAMs on improving the device performance of FETs.

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Carbon dot – Unique reinforcing filler for polymer with special reference to physico-mechanical properties

Publication date: 10 March 2017
Source:Polymer, Volume 112
Author(s): P.R. Sreenath, Seema Singh, M.S. Satyanarayana, Prolay Das, K. Dinesh Kumar
This work reports the reinforcing efficiency of carbon dots (CDs) in carboxylated acrylonitrile butadiene (XNBR) latex at very low concentration. Amine and carboxyl functionalized CDs have been synthesized from citric acid and glycine. The CDs are covalently conjugated to XNBR latex using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) and N-hydroxysuccinimide (NHS) as coupling agents. The covalent conjugation of CDs with XNBR latex has been confirmed by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and X-ray photoelectron spectroscopy (XPS). The optical properties of CDs and XNBR-CDs conjugate have been characterized by ultraviolet (UV) - visible, fluorescence spectroscopy, time-resolved fluorescence spectrophotometer and haze meter. The tensile stress-strain properties of XNBR latex dramatically increases by the addition of CDs to XNBR latex. The maximum tensile stress of 2 phr of CDs loaded XNBR latex is nearly 215% higher than the maximum tensile stress of neat XNBR latex. There is a concomitant decrease in the tan δ peak height and increase in the tan δ peak temperature of XNBR latex with the incorporation of CDs to XNBR latex. In addition, the storage modulus (G′) value of sample containing 2 phr of CDs is 161% higher than the storage modulus value (G′) of neat XNBR latex. The onset of degradation temperature (Ti) value of sample containing 4 phr of CDs is 40 °C higher than the Ti value of neat XNBR latex. On the other hand, the maximum degradation temperature (Tmax) of XNBR latex containing 1 phr of CDs is 11 °C higher than the Tmax value of neat XNBR latex. Morphology of pristine CDs and XNBR-CDs conjugate has been analyzed using transmission electron microscopy (TEM). To the best of our knowledge, this is the first report which analyzes the effect of CDs on the physico-mechanical properties of elastomer contrary to the other novel fillers of carbon family.

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