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  • 1
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Marc Baaden, Olivier Delalande, Nicolas Ferey, Samuela Pasquali, Jérôme Waldispühl, Antoine Taly
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 2
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Elizabeth C. Lee, Ali Arab, Sandra M. Goldlust, Cécile Viboud, Bryan T. Grenfell, Shweta Bansal The surveillance of influenza activity is critical to early detection of epidemics and pandemics and the design of disease control strategies. Case reporting through a voluntary network of sentinel physicians is a commonly used method of passive surveillance for monitoring rates of influenza-like illness (ILI) worldwide. Despite its ubiquity, little attention has been given to the processes underlying the observation, collection, and spatial aggregation of sentinel surveillance data, and its subsequent effects on epidemiological understanding. We harnessed the high specificity of diagnosis codes in medical claims from a database that represented 2.5 billion visits from upwards of 120,000 United States healthcare providers each year. Among influenza seasons from 2002-2009 and the 2009 pandemic, we simulated limitations of sentinel surveillance systems such as low coverage and coarse spatial resolution, and performed Bayesian inference to probe the robustness of ecological inference and spatial prediction of disease burden. Our models suggest that a number of socio-environmental factors, in addition to local population interactions, state-specific health policies, as well as sampling effort may be responsible for the spatial patterns in U.S. sentinel ILI surveillance. In addition, we find that biases related to spatial aggregation were accentuated among areas with more heterogeneous disease risk, and sentinel systems designed with fixed reporting locations across seasons provided robust inference and prediction. With the growing availability of health-associated big data worldwide, our results suggest mechanisms for optimizing digital data streams to complement traditional surveillance in developed settings and enhance surveillance opportunities in developing countries.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 3
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Phimon Atsawasuwan, Paul Lazari, Yinghua Chen, Xiaofeng Zhou, Grace Viana, Carla A. Evans Secretory microRNAs (miRNAs) have been used increasingly as biomarkers for cancers, autoimmune diseases and inflammatory diseases. They are reported as being freely circulated or encapsulated in microvesicles such as exosomes. This study was performed to elucidate the presence of miRNAs with exosomes in human gingival crevicular fluid (GCF), and the expression profile of miRNA-29 during orthodontic tooth movement. Four healthy volunteer and fifteen orthodontic patients were enrolled in the study. Secretory miRNA in GCF was collected and analyzed using a bioanalyzer, realtime PCR and Western blot analysis. The expression profile of secretory miR-29 family in GCF was analyzed during the course of canine retraction for 6 weeks. The results demonstrated the presence of miRNAs in the GCF. After series of ultracentrifugation and RT-PCR array, exosome-depleted fractions and pellets were isolated and we found that secretory miRNAs were detected in both the exosome-associated fraction and the exosome-depleted supernatant fraction; however, the concentration of miRNAs was higher in the exosome-associated fraction than in the exosome-depleted fraction suggesting a close association between the secretory miRNAs and exosomes in GCF. We also demonstrated the increased expression profiles of miR-29 family during six weeks of orthodontic tooth movement in humans. Secretory miRNAs are present in GCF and secretory miRNA-29 family expression profiles increase during the tooth movement in humans. Secretory miRNA-29 in GCF could serve as potential biomarkers for periodontal remodeling.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2018-03-09
    Description: by Laia Calvó-Perxas, Joan Vilalta-Franch, Howard Litwin, Oriol Turró-Garriga, Pedro Mira, Josep Garre-Olmo In Europe, informal caregiving is frequent and is expected to grow. Caregiving has an impact on caregivers’ health, but its effect may vary according to the policies of support that are available to caregivers. The aim of this study was to assess the association between the policies of support to caregivers available in 12 European countries and the health of caregivers, considering separately the policies based on financial help and those based on training and other non- financial services. We used data from 13,507 caregivers from 12 European countries from the fifth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) to build a path model. Poor health among caregivers was associated with living in a family-based care country (β = 0.50; 95% CI = 0.42–0.59), and with an increased extent of caregiving (β = 0.18; 95% CI = 0.15–0.22). Non-financial support measures seem to have a larger protective impact (β = –0.33; 95% CI = –0.38 - –0.28) on the health of caregivers than do financial support measures (β = 0.03; 95% CI = 0.01–0.04), regardless of the gender of the caregiver. According to our results, the currently available policies of support associated with better health among caregivers are those that: 1) provide them with some free time, 2) help them to deal emotionally with caregiving, and 3) give them skills to both improve the care situation and to deal with it better.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 5
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Sau Ha Cheung, James Yun Wong Lau S -sulfhydration is a signalling pathway of hydrogen sulfide (H 2 S), which is suggested as an anti-atherogenic molecule that may protect against atherosclerosis. The identification of S -sulfhydrated proteins by proteomic approach could be a major step towards understanding the mechanisms of H 2 S in response to atherosclerosis. The present study studied targeted S -sulfhydrated proteins using the modified biotin switch method followed by matrix-assisted laser desorption/ionisation time of flight tandem mass spectrometry identification. The results showed that H 2 S can protect against atherosclerosis by reducing body weight gain and alleviating aortic plaque formation. In addition, H 2 S treatment can increase aortic protein S -sulfhydration. Seventy targeted S -sulfhydrated aortic proteins were identified, mainly involved in metabolism, stimulus response and biological regulation, as determined by gene ontology database analysis. H 2 S also induced S -sulfhydration of glutathione peroxidase 1 and further reduced lipid peroxidation and increased antioxidant defence in the aorta by prompting glutathione synthesis. Our data suggest that H 2 S is a cardiovascular-protective molecule that S -sulfhydrates a subset of proteins that are mainly responsible for lipid metabolism and exerts its cytoprotective effects to clear free radicals and inhibit oxidative stress through cysteine S -sulfhydration.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 6
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Antonino Malacrinò, Orlando Campolo, Raul F. Medina, Vincenzo Palmeri Microorganisms are acknowledged for their role in shaping insects’ evolution, life history and ecology. Previous studies have shown that microbial communities harbored within insects vary through ontogenetic development and among insects feeding on different host-plant species. In this study, we characterized the bacterial microbiota of the highly polyphagous Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae), at different instars and when feeding on different host-plant species. Our results show that the bacterial microbiota hosted within the Mediterranean fruit fly differs among instars and host-plant species. Most of the bacteria harbored by the Mediterranean fruit fly belong to the phylum Proteobacteria, including genera of Alphaproteobacteria such as Acetobacter and Gluconobacter ; Betaprotobacteria such as Burkholderia and Gammaproteobacteria such as Pseudomonas .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2018-03-09
    Description: by Katarzyna Bojarska, Ralph Kuehn, Małgorzata A. Gazda, Nozomu J. Sato, Yuji Okahisa, Keita D. Tanaka, Alfredo Attisano, Roman Gula, Keisuke Ueda, Jörn Theuerkauf Extra-pair copulation can increase genetic diversity and offspring fitness. However, it may also increase intra-nest variability in avian hosts of brood parasites, which can decrease the discrimination ability of host parents towards the parasite. In New Caledonia, the Fan-tailed Gerygone ( Gerygone flavolateralis ), which is parasitized by the Shining Bronze-cuckoo ( Chalcites lucidus ), has two nestling morphs, dark and bright, that can occur in monomorphic and polymorphic broods. Gerygone parents recognize and eject parasite nestlings from their nest, but the presence of polymorphic broods may increase the chances of recognition errors. Using 17 microsatellite markers, we investigated the mating system of the Fan-tailed Gerygone to understand the mechanisms underlying nestling polymorphism. We hypothesised that extra-pair copulations would lead to a higher proportion of polymorphic broods caused by higher genetic variability, thus creating a trade-off between genetic benefits and host defence reliability. Extra-pair paternity occurred in 6 of 36 broods, which resulted in 6 of 69 offspring sired by extra-pair males. Broods with and without mixed paternity were comparably often parasitized. Extra-pair paternity did not influence the proportions of bright, dark and polymorphic broods. Compared to bright siblings in polymorphic broods, dark nestlings tended to have lower heterozygosity, particularly in loci associated with skin coloration. The results also suggested that there is no obstacle for genetic exchange between individuals from forest and savannah, possibly due to dispersal of offspring. We conclude that the Fan-tailed Gerygone is a socially monogamous species with a low rate of extra-pair paternity compared to closely related species. Extra-pair paternity increased offspring genetic variability without measurable associated costs by brood parasitism. The results highlight the importance of studying host mating systems to assess the trade-offs between host defence and offspring fitness in co-evolutionary arms races.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Nicky O’Boyle, Erin Sutherland, Catherine C. Berry, Robert L. Davies Respiratory tract infections are of significant concern in the agriculture industry. There is a requirement for the development of well-characterised in vitro epithelial cell culture models in order to dissect the diverse molecular interactions occurring at the host-pathogen interface in airway epithelia. We have analysed key factors that influence growth and differentiation of ovine tracheal epithelial cells in an air-liquid interface (ALI) culture system. Cellular differentiation was assessed at 21 days post-ALI, a time-point which we have previously shown to be sufficient for differentiation in standard growth conditions. We identified a dose-dependent response to epidermal growth factor (EGF) in terms of both epithelial thickening and ciliation levels. Maximal ciliation levels were observed with 25 ng ml -1 EGF. We identified a strict requirement for retinoic acid (RA) in epithelial differentiation as RA exclusion resulted in the formation of a stratified squamous epithelium, devoid of cilia. The pore-density of the growth substrate also had an influence on differentiation as high pore-density inserts yielded higher levels of ciliation and more uniform cell layers than low pore-density inserts. Differentiation was also improved by culturing the cells in an atmosphere of sub-ambient oxygen concentration. We compared two submerged growth media and observed differences in the rate of proliferation/expansion, barrier formation and also in terminal differentiation. Taken together, these results indicate important differences between the response of ovine tracheal epithelial cells and other previously described airway epithelial models, to a variety of environmental conditions. These data also indicate that the phenotype of ovine tracheal epithelial cells can be tailored in vitro by precise modulation of growth conditions, thereby yielding a customisable, potential infection model.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 9
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Ulf Kai Mertens, Andreas Voss, Stefan Radev We give an overview of the basic principles of approximate Bayesian computation (ABC), a class of stochastic methods that enable flexible and likelihood-free model comparison and parameter estimation. Our new open-source software called ABrox is used to illustrate ABC for model comparison on two prominent statistical tests, the two-sample t-test and the Levene-Test. We further highlight the flexibility of ABC compared to classical Bayesian hypothesis testing by computing an approximate Bayes factor for two multinomial processing tree models. Last but not least, throughout the paper, we introduce ABrox using the accompanied graphical user interface.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2018-03-09
    Description: by Zhulong Hu, Yuang Wang, Qiaopeng Tang, Xiaodan Yang, Yali Qin, Mingzhou Chen Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway. Furthermore, we found that inclusion body (IB) formation by the interaction of the nucleoprotein (N) and phosphoprotein (P) of HPIV3 correlated with SG suppression. In addition, co-expression of P with N L478A (a point mutant of N, which is unable to form IBs with P) or with NΔN10 (lacking N-terminal 10 amino acids of N, which could form IBs with P but was unable to synthesize or shield viral RNAs) failed to inhibit SG formation, suggesting that inhibition of SG formation also correlates with the capacity of IBs to synthesize and shield viral RNAs. Therefore, we provide a model whereby viral IBs escape the antiviral effect of SGs by concealing their own newly synthesized viral RNAs and offer new insights into the emerging role of IBs in viral replication.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 11
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-09
    Description: by Martina Bradic, Jane M. Carlton
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 12
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-12
    Description: by Chunling Lu, Zhihui Li, Vikram Patel In an analysis of data from the Creditor Reporting System, Chunling Lu and colleagues investigate the level of development assistance from high-income countries towards child and adolescent mental health in low- and middle-income countries.
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
    Topics: Medicine
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  • 13
    Publication Date: 2018-03-12
    Description: by Brant M. Wagener, Parker J. Hu, Joo-Yeun Oh, Cilina A. Evans, Jillian R. Richter, Jaideep Honavar, Angela P. Brandon, Judy Creighton, Shannon W. Stephens, Charity Morgan, Randal O. Dull, Marisa B. Marques, Jeffrey D. Kerby, Jean-Francois Pittet, Rakesh P. Patel Background Trauma is the leading cause of death and disability in patients aged 1–46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic efficacy, increased severity of organ injury, and increased bacterial infection are associated with transfusion of large volumes of stored RBCs, although the mechanisms are not fully understood. Methods and findings We developed a murine model of trauma hemorrhage (TH) followed by resuscitation with plasma and leukoreduced RBCs (in a 1:1 ratio) that were banked for 0 (fresh) or 14 (stored) days. Two days later, lungs were infected with Pseudomonas aeruginosa K-strain (PAK). Resuscitation with stored RBCs significantly increased the severity of lung injury caused by P . aeruginosa , as demonstrated by higher mortality (median survival 35 h for fresh RBC group and 8 h for stored RBC group; p 〈 0.001), increased pulmonary edema (mean [95% CI] 106.4 μl [88.5–124.3] for fresh RBCs and 192.5 μl [140.9–244.0] for stored RBCs; p = 0.003), and higher bacterial numbers in the lung (mean [95% CI] 1.2 × 10 7 [−1.0 × 10 7 to 2.5 × 10 7 ] for fresh RBCs and 3.6 × 10 7 [2.5 × 10 7 to 4.7 × 10 7 ] for stored RBCs; p = 0.014). The mechanism underlying this increased infection susceptibility and severity was free-heme-dependent, as recombinant hemopexin or pharmacological inhibition or genetic deletion of toll-like receptor 4 (TLR4) during TH and resuscitation completely prevented P . aeruginosa– induced mortality after stored RBC transfusion ( p 〈 0.001 for all groups relative to stored RBC group). Evidence from studies transfusing fresh and stored RBCs mixed with stored and fresh RBC supernatants, respectively, indicated that heme arising both during storage and from RBC hemolysis post-resuscitation plays a role in increased mortality after PAK ( p 〈 0.001). Heme also increased endothelial permeability and inhibited macrophage-dependent phagocytosis in cultured cells. Stored RBCs also increased circulating high mobility group box 1 (HMGB1; mean [95% CI] 15.4 ng/ml [6.7–24.0] for fresh RBCs and 50.3 ng/ml [12.3–88.2] for stored RBCs), and anti-HMGB1 blocking antibody protected against PAK-induced mortality in vivo ( p = 0.001) and restored macrophage-dependent phagocytosis of P . aeruginosa in vitro. Finally, we showed that TH patients, admitted to the University of Alabama at Birmingham ER between 1 January 2015 and 30 April 2016 ( n = 50), received high micromolar–millimolar levels of heme proportional to the number of units transfused, sufficient to overwhelm endogenous hemopexin levels early after TH and resuscitation. Limitations of the study include lack of assessment of temporal changes in different products of hemolysis after resuscitation and the small sample size precluding testing of associations between heme levels and adverse outcomes in resuscitated TH patients. Conclusions We provide evidence that large volume resuscitation with stored blood, compared to fresh blood, in mice increases mortality from subsequent pneumonia, which occurs via mechanisms sensitive to hemopexin and TLR4 and HMGB1 inhibition.
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
    Topics: Medicine
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  • 14
    Publication Date: 2018-03-12
    Description: by Kimberly Y. Won, Keri Robinson, Katy L. Hamlin, Joseph Tufa, Margaret Seespesara, Ryan E. Wiegand, Katherine Gass, Joseph Kubofcik, Thomas B. Nutman, Patrick J. Lammie, Saipale Fuimaono Background Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA). A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS). Methodology TAS was first conducted in American Samoa in 2011 (TAS 1) and a repeat TAS was carried out in 2015 (TAS 2). Circulating filarial antigen (CFA) and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa. Principal findings A total of 1,134 and 864 children (5–10 years old) were enrolled in TAS 1 and TAS 2, respectively. Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. Results of both surveys were below the threshold for which MDA was warranted. Additionally, 1,112 and 836 dried blood spots from TAS 1 and TAS 2, respectively were tested for antibodies to Wb123, Bm14 and Bm33 by luciferase immunoprecipitation system (LIPS) assay and multiplex bead assay. In 2011, overall prevalence of responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% (p
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 15
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-12
    Description: by Jordana L. Burdon Bailey, Luke Gamble, Andrew D. Gibson, Barend M. deC. Bronsvoort, Ian G. Handel, Richard J. Mellanby, Stella Mazeri Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 16
    Publication Date: 2018-03-12
    Description: by Stephen R. Welch, Ayan K. Chakrabarti, Lisa Wiggleton Guerrero, Harley M. Jenks, Michael K. Lo, Stuart T. Nichol, Christina F. Spiropoulou, César G. Albariño Sosuga virus (SOSV) is a recently discovered zoonotic paramyxovirus isolated from a single human case in 2012; it has been ecologically and epidemiologically associated with transmission by the Egyptian rousette bat ( Rousettus aegyptiacus ). Bats have long been recognized as sources of novel zoonotic pathogens, including highly lethal paramyxoviruses like Nipah virus (NiV) and Hendra virus (HeV). The ability of SOSV to cause severe human disease supports the need for studies on SOSV pathogenesis to better understand the potential impact of this virus and to identify effective treatments. Here we describe a reverse genetics system for SOSV comprising a minigenome-based assay and a replication-competent infectious recombinant reporter SOSV that expresses the fluorescent protein ZsGreen1 in infected cells. First, we used the minigenome assay to rapidly screen for compounds inhibiting SOSV replication at biosafety level 2 (BSL-2). The antiviral activity of candidate compounds was then tested against authentic viral replication using the reporter SOSV at BSL-3. We identified several compounds with anti-SOSV activity, several of which also inhibit NiV and HeV. Alongside its utility in screening for potential SOSV therapeutics, the reverse genetics system described here is a powerful tool for analyzing mechanisms of SOSV pathogenesis, which will facilitate our understanding of how to combat the potential public health threats posed by emerging bat-borne paramyxoviruses.
    Print ISSN: 1935-2727
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  • 17
    Publication Date: 2018-03-12
    Description: by Norio Kasai, Osamu Kondo, Koichi Suzuki, Yoshinori Aoki, Norihisa Ishii, Masamichi Goto Background Facial deformation as a sequela of leprosy is caused not only by a saddle nose but also by regression of the maxilla, as well documented in paleopathological observations of excavated skeletal remains of patients with leprosy. However, maxillary changes in living patients have been evaluated only by the subjective visual grading. Here, we attempted to evaluate maxillary bone deformation in patients with leprosy using three-dimensional computed tomography (3D-CT). Methods Three-dimensional images centered on the maxilla were reconstructed using multiplanar reconstruction methods in former patients with leprosy (n = 10) and control subjects (n = 5); the anterior-posterior length of the maxilla (M A-P ) was then measured. The difference between the M A-P of the patients and those of controls was evaluated after compensating for individual skull size. These findings were also compared with those from previous paleopathological studies. Findings Three former patients with lepromatous leprosy showed marked atrophy of the maxilla at the prosthion (-8.6, -11.1 and -17.9 mm) which corresponded with the visual appearance of the maxillary deformity, and these results were consistent with paleopathological findings of excavated skeletal remains. Additionally, the precise bone defects of the maxilla could be individually calculated for accurate reconstructive surgery. Interpretation We have successfully illustrated maxillary bone deformities in living patients with leprosy. This study also confirmed the maxillary regression described in paleopathological studies.
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  • 18
    Publication Date: 2018-03-12
    Description: by Gilbert Adjimon Ayelo, Esai Anagonou, Anita Carolle Wadagni, Yves Thierry Barogui, Ange Dodji Dossou, Jean Gabin Houezo, Julia Aguiar, Roch Christian Johnson, Raoul Saizonou, Kingsley Asiedu, Ghislain Emmanuel Sopoh Background Nigeria is one of the countries endemic for Buruli ulcer (BU) in West Africa but did not have a control programme until recently. As a result, BU patients often access treatment services in neighbouring Benin where dedicated health facilities have been established to provide treatment free of charge for BU patients. This study aimed to describe the epidemiological, clinical, biological and therapeutic characteristics of cases from Nigeria treated in three of the four treatment centers in Benin. Methodology/Principal findings A series of 82 BU cases from Nigeria were treated in three centres in Benin during 2006–2016 and are retrospectively described. The majority of these patients came from Ogun and Lagos States which border Benin. Most of the cases were diagnosed with ulcerative lesions (80.5%) and WHO category III lesions (82.9%); 97.5% were healed after a median hospital stay of 46 days (interquartile range [IQR]: 32–176 days). Conclusions/Significance This report adds to the epidemiological understanding of BU in Nigeria in the hope that the programme will intensify efforts aimed at early case detection and treatment.
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  • 19
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-12
    Description: by Nicole Stichling, Maarit Suomalainen, Justin W. Flatt, Markus Schmid, Martin Pacesa, Silvio Hemmi, Wolfgang Jungraithmayr, Mareike D. Maler, Marina A. Freudenberg, Andreas Plückthun, Tobias May, Mario Köster, György Fejer, Urs F. Greber Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.
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  • 20
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-13
    Description: by Anne Keitel, Joachim Gross, Christoph Kayser During online speech processing, our brain tracks the acoustic fluctuations in speech at different timescales. Previous research has focused on generic timescales (for example, delta or theta bands) that are assumed to map onto linguistic features such as prosody or syllables. However, given the high intersubject variability in speaking patterns, such a generic association between the timescales of brain activity and speech properties can be ambiguous. Here, we analyse speech tracking in source-localised magnetoencephalographic data by directly focusing on timescales extracted from statistical regularities in our speech material. This revealed widespread significant tracking at the timescales of phrases (0.6–1.3 Hz), words (1.8–3 Hz), syllables (2.8–4.8 Hz), and phonemes (8–12.4 Hz). Importantly, when examining its perceptual relevance, we found stronger tracking for correctly comprehended trials in the left premotor (PM) cortex at the phrasal scale as well as in left middle temporal cortex at the word scale. Control analyses using generic bands confirmed that these effects were specific to the speech regularities in our stimuli. Furthermore, we found that the phase at the phrasal timescale coupled to power at beta frequency (13–30 Hz) in motor areas. This cross-frequency coupling presumably reflects top-down temporal prediction in ongoing speech perception. Together, our results reveal specific functional and perceptually relevant roles of distinct tracking and cross-frequency processes along the auditory–motor pathway.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 21
    Publication Date: 2018-03-13
    Description: by Hao Ge, Pingping Wu, Hong Qian, Sunney Xiaoliang Xie Within an isogenic population, even in the same extracellular environment, individual cells can exhibit various phenotypic states. The exact role of stochastic gene-state switching regulating the transition among these phenotypic states in a single cell is not fully understood, especially in the presence of positive feedback. Recent high-precision single-cell measurements showed that, at least in bacteria, switching in gene states is slow relative to the typical rates of active transcription and translation. Hence using the lac operon as an archetype, in such a region of operon-state switching, we present a fluctuating-rate model for this classical gene regulation module, incorporating the more realistic operon-state switching mechanism that was recently elucidated. We found that the positive feedback mechanism induces bistability (referred to as deterministic bistability), and that the parameter range for its occurrence is significantly broadened by stochastic operon-state switching. We further show that in the absence of positive feedback, operon-state switching must be extremely slow to trigger bistability by itself. However, in the presence of positive feedback, which stabilizes the induced state, the relatively slow operon-state switching kinetics within the physiological region are sufficient to stabilize the uninduced state, together generating a broadened parameter region of bistability (referred to as stochastic bistability). We illustrate the opposite phenotype-transition rate dependence upon the operon-state switching rates in the two types of bistability, with the aid of a recently proposed rate formula for fluctuating-rate models. The rate formula also predicts a maximal transition rate in the intermediate region of operon-state switching, which is validated by numerical simulations in our model. Overall, our findings suggest a biological function of transcriptional “variations” among genetically identical cells, for the emergence of bistability and transition between phenotypic states.
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-13
    Description: by Jinbo Chen, Uwe Scholz, Ruonan Zhou, Matthias Lange In order to access and filter content of life-science databases, full text search is a widely applied query interface. But its high flexibility and intuitiveness is paid for with potentially imprecise and incomplete query results. To reduce this drawback, query assistance systems suggest those combinations of keywords with the highest potential to match most of the relevant data records. Widespread approaches are syntactic query corrections that avoid misspelling and support expansion of words by suffixes and prefixes. Synonym expansion approaches apply thesauri, ontologies, and query logs. All need laborious curation and maintenance. Furthermore, access to query logs is in general restricted. Approaches that infer related queries by their query profile like research field, geographic location, co-authorship, affiliation etc. require user’s registration and its public accessibility that contradict privacy concerns. To overcome these drawbacks, we implemented LAILAPS-QSM, a machine learning approach that reconstruct possible linguistic contexts of a given keyword query. The context is referred from the text records that are stored in the databases that are going to be queried or extracted for a general purpose query suggestion from PubMed abstracts and UniProt data. The supplied tool suite enables the pre-processing of these text records and the further computation of customized distributed word vectors. The latter are used to suggest alternative keyword queries. An evaluated of the query suggestion quality was done for plant science use cases. Locally present experts enable a cost-efficient quality assessment in the categories trait, biological entity, taxonomy, affiliation, and metabolic function which has been performed using ontology term similarities. LAILAPS-QSM mean information content similarity for 15 representative queries is 0.70, whereas 34% have a score above 0.80. In comparison, the information content similarity for human expert made query suggestions is 0.90. The software is either available as tool set to build and train dedicated query suggestion services or as already trained general purpose RESTful web service. The service uses open interfaces to be seamless embeddable into database frontends. The JAVA implementation uses highly optimized data structures and streamlined code to provide fast and scalable response for web service calls. The source code of LAILAPS-QSM is available under GNU General Public License version 2 in Bitbucket GIT repository: https://bitbucket.org/ipk_bit_team/bioescorte-suggestion
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  • 23
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-13
    Description: by Britta U. Westner, Sarang S. Dalal, Simon Hanslmayr, Tobias Staudigl Single-trial analyses have the potential to uncover meaningful brain dynamics that are obscured when averaging across trials. However, low signal-to-noise ratio (SNR) can impede the use of single-trial analyses and decoding methods. In this study, we investigate the applicability of a single-trial approach to decode stimulus modality from magnetoencephalographic (MEG) high frequency activity. In order to classify the auditory versus visual presentation of words, we combine beamformer source reconstruction with the random forest classification method. To enable group level inference, the classification is embedded in an across-subjects framework. We show that single-trial gamma SNR allows for good classification performance (accuracy across subjects: 66.44%). This implies that the characteristics of high frequency activity have a high consistency across trials and subjects. The random forest classifier assigned informational value to activity in both auditory and visual cortex with high spatial specificity. Across time, gamma power was most informative during stimulus presentation. Among all frequency bands, the 75 Hz 95 Hz band was the most informative frequency band in visual as well as in auditory areas. Especially in visual areas, a broad range of gamma frequencies (55 Hz 125 Hz) contributed to the successful classification. Thus, we demonstrate the feasibility of single-trial approaches for decoding the stimulus modality across subjects from high frequency activity and describe the discriminative gamma activity in time, frequency, and space.
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  • 24
    Publication Date: 2018-03-13
    Description: by Michael Pablo, Samuel A. Ramirez, Timothy C. Elston Polarity establishment, the spontaneous generation of asymmetric molecular distributions, is a crucial component of many cellular functions. Saccharomyces cerevisiae (yeast) undergoes directed growth during budding and mating, and is an ideal model organism for studying polarization. In yeast and many other cell types, the Rho GTPase Cdc42 is the key molecular player in polarity establishment. During yeast polarization, multiple patches of Cdc42 initially form, then resolve into a single front. Because polarization relies on strong positive feedback, it is likely that the amplification of molecular-level fluctuations underlies the generation of multiple nascent patches. In the absence of spatial cues, these fluctuations may be key to driving polarization. Here we used particle-based simulations to investigate the role of stochastic effects in a Turing-type model of yeast polarity establishment. In the model, reactions take place either between two molecules on the membrane, or between a cytosolic and a membrane-bound molecule. Thus, we developed a computational platform that explicitly simulates molecules at and near the cell membrane, and implicitly handles molecules away from the membrane. To evaluate stochastic effects, we compared particle simulations to deterministic reaction-diffusion equation simulations. Defining macroscopic rate constants that are consistent with the microscopic parameters for this system is challenging, because diffusion occurs in two dimensions and particles exchange between the membrane and cytoplasm. We address this problem by empirically estimating macroscopic rate constants from appropriately designed particle-based simulations. Ultimately, we find that stochastic fluctuations speed polarity establishment and permit polarization in parameter regions predicted to be Turing stable. These effects can operate at Cdc42 abundances expected of yeast cells, and promote polarization on timescales consistent with experimental results. To our knowledge, our work represents the first particle-based simulations of a model for yeast polarization that is based on a Turing mechanism.
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  • 25
    Publication Date: 2018-03-13
    Description: by The PLOS Biology Staff
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 26
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-13
    Description: by Guillaume Pernelle, Wilten Nicola, Claudia Clopath Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex.
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  • 27
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    Publication Date: 2018-03-13
    Description: by Damla Tas, Luca Stickley, Federico Miozzo, Rafael Koch, Nicolas Loncle, Virginie Sabado, Bettina Gnägi, Emi Nagoshi Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson’s disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila . We show that dFOXO null mutants exhibit a selective loss of DA neurons in the subgroup crucial for locomotion, the protocerebral anterior medial (PAM) cluster, during development as well as in adulthood. PAM neuron-targeted adult-restricted knockdown demonstrates that dFOXO in adult PAM neurons tissue-autonomously promotes neuronal survival during aging. We further show that dFOXO and the bHLH-TF 48-related-2 (FER2) act in parallel to protect PAM neurons from different forms of cellular stress. Remarkably, however, dFOXO and FER2 share common downstream processes leading to the regulation of autophagy and mitochondrial morphology. Thus, overexpression of one can rescue the loss of function of the other. These results indicate a role of dFOXO in neuroprotection and highlight the notion that multiple genetic and environmental factors interact to increase the risk of DA neuron degeneration and the development of PD.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 28
    Publication Date: 2018-03-13
    Description: by Sangyong Choi, Ya-Mei Hu, Mark E. Corkins, Amy E. Palmer, Amanda J. Bird Zinc is an essential trace element that is required for the function of a large number of proteins. As these zinc-binding proteins are found within the cytosol and organelles, all eukaryotes require mechanisms to ensure that zinc is delivered to organelles, even under conditions of zinc deficiency. Although many zinc transporters belonging to the Cation Diffusion Facilitator (CDF) families have well characterized roles in transporting zinc into the lumens of intracellular compartments, relatively little is known about the mechanisms that maintain organelle zinc homeostasis. The fission yeast Schizosaccharomyces pombe is a useful model system to study organelle zinc homeostasis as it expresses three CDF family members that transport zinc out of the cytosol into intracellular compartments: Zhf1, Cis4, and Zrg17. Zhf1 transports zinc into the endoplasmic reticulum, and Cis4 and Zrg17 form a heterodimeric complex that transports zinc into the cis-Golgi. Here we have used the high and low affinity ZapCY zinc-responsive FRET sensors to examine cytosolic zinc levels in yeast mutants that lack each of these CDF proteins. We find that deletion of cis4 or zrg17 leads to higher levels of zinc accumulating in the cytosol under conditions of zinc deficiency, whereas deletion of zhf1 results in zinc accumulating in the cytosol when zinc is not limiting. We also show that the expression of cis4 , zrg17 , and zhf1 is independent of cellular zinc status. Taken together our results suggest that the Cis4/Zrg17 complex is necessary for zinc transport out of the cytosol under conditions of zinc-deficiency, while Zhf1 plays the dominant role in removing zinc from the cytosol when labile zinc is present. We propose that the properties and/or activities of individual CDF family members are fine-tuned to enable cells to control the flux of zinc out of the cytosol over a broad range of environmental zinc stress.
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  • 29
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-13
    Description: by Michail Zaboikin, Carl Freter, Narasimhachar Srinivasakumar
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 30
    Publication Date: 2018-03-13
    Description: by Lloyd Einsiedel, Hai Pham, Kim Wilson, Rebecca Walley, Jocelyn Turpin, Charles Bangham, Antoine Gessain, Richard J. Woodman Background The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). Methodology/Principal findings 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured.Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 10 5 peripheral blood leukocytes (log-rank χ 2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Conclusion/Significance Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.
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  • 31
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    Publication Date: 2018-03-13
    Description: by Gajenthiran Sinnathamby, Gemma Henderson, Saleh Umair, Peter Janssen, Ross Bland, Heather Simpson
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 32
    Publication Date: 2018-03-13
    Description: by Mirco Floreani, Enrico Rejc, Paolo Taboga, Alessandro Ganzini, Rado Pišot, Bostjan Šimunič, Gianni Biolo, Carlo Reggiani, Angelina Passaro, Marco Narici, Joern Rittweger, Pietro Enrico di Prampero, Stefano Lazzer In this study, we investigated: i) the effects of bed rest and a subsequent physical training program on metabolic cost (Cw), mechanical work and efficiency during walking in older and young men; ii) the mechanisms underlying the higher Cw observed in older than young men.Twenty-three healthy male subjects (N = 16 older adults, age 59.6±3.4 years; N = 7 young, age: 23.1±2.9 years) participated in this study. The subjects underwent 14 days of bed rest followed by two weeks of physical training (6 sessions). Cw, mechanical work, efficiency, and co-contraction time of proximal muscles (vastus lateralis and biceps femoris) and distal muscles (gastrocnemius medialis and tibialis anterior) were measured during walking at 0.83, 1.11, 1.39, 1.67 m·s -1 before bed rest (pre-BR), after bed rest (post-BR) and after physical training (post-PT).No effects of bed rest and physical training were observed on the analysed parameters in either group. Older men showed higher Cw and lower efficiency at each speed (average +25.1 and -20.5%, P
    Electronic ISSN: 1932-6203
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  • 33
    Publication Date: 2018-03-13
    Description: by Ling Sun, Xuejun Zhou, Jianguang Jiang, Xuan Zang, Xin Chen, Haiyan Li, Haitao Cao, Qingjie Wang Background Growth differentiation factor-15 (GDF-15) is an emerging biomarker for risk stratification in cardiovascular disease. Contrast-induced acute kidney injury (AKI) is an important complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). In this retrospectively observational study, we aimed to determine the role of GDF-15 and the risk of AKI in acute myocardial infarction (AMI) patients. Methods The medical records of 1195 patients with AMI were reviewed. After exclusion criteria, a total of 751 eligible patients who underwent CAG or PCI were studied. Preoperative clinical parameters including GDF-15 levels were recorded. Multivariate logistic regression analysis was used to identify the risk factors of AKI. Subsequently, to reduce a potential selection bias and to balance differences between the two groups, a propensity score-matched analysis was performed. We recorded the 30-day all-cause mortality of the total study population. Kaplan-Meier analysis was performed to identify the association between short term survival in AMI patients and GDF-15 level. Results Among 751 enrolled patients, 106 patients (14.1%) developed AKI. Patients were divided into two groups: AKI group (n = 106) and non-AKI group (n = 645). GDF-15 levels were significantly higher in AKI group compared to non-AKI group (1328.2 ± 349.7 ng/L vs. 1113.0 ± 371.3 ng/L, P
    Electronic ISSN: 1932-6203
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  • 34
    Publication Date: 2018-03-13
    Description: by Patrick Grüneberg, Hideki Kadone, Naomi Kuramoto, Tomoyuki Ueno, Yasushi Hada, Masashi Yamazaki, Yoshiyuki Sankai, Kenji Suzuki Humans employ various control strategies to initiate and maintain bodily movement. In case that the normal gait function is impaired, exoskeleton robots provide motor assistance during therapy. While the robotic control system builds on kinematic gait functions, the patient’s voluntary efforts to initiate motion also contribute to the effectiveness of the therapy process. However, it is currently not well understood how voluntary initiation as a subjective capacity affects the physiological level of motor control. In order to understand the functional nexus between voluntary initiation and motor control, we interviewed patients undergoing robotic gait rehabilitation with the HAL exoskeleton robot about their experience and command of voluntarily initiating forward gait while using the HAL system. Their reports provide phenomenal evidence for voluntary initiation as a distinct cognitive act that comes as phenomenal performance. Furthermore, phenomenal evidence about the functional relation of intention and initiation correlates with FIM-M gait scores. Based on the assumption that HAL reduces control-related difficulties of voluntarily initiating joint movement, we identified two cognitive control strategies, shaping and compensation of gait, that imply a heterarchic organization of the human system of action control.
    Electronic ISSN: 1932-6203
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  • 35
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    Publication Date: 2018-03-13
    Description: by Pingyu Nan, Darragh M. Walsh, Kerry A. Landman, Barry D. Hughes Motivated by in vitro time–lapse images of ovarian cancer spheroids inducing mesothelial cell clearance, the traditional agent–based model of cell migration, based on simple volume exclusion, was extended to include the possibility that a cell seeking to move into an occupied location may push the resident cell, and any cells neighbouring it, out of the way to occupy that location. In traditional discrete models of motile cells with volume exclusion such a move would be aborted. We introduce a new shoving mechanism which allows cells to choose the direction to shove cells that expends the least amount of shoving effort (to account for the likely resistance of cells to being pushed). We call this motility rule ‘smart shoving’. We examine whether agent–based simulations of different shoving mechanisms can be distinguished on the basis of single realisations and averages over many realisations. We emphasise the difficulty in distinguishing cell mechanisms from cellular automata simulations based on snap–shots of cell distributions, site–occupancy averages and the evolution of the number of cells of each species averaged over many realisations. This difficulty suggests the need for higher resolution cell tracking.
    Electronic ISSN: 1932-6203
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  • 36
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    Publication Date: 2018-03-13
    Description: by Wenbiao Wang, Feng Xiao, Pin Wan, Pan Pan, Yecheng Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 37
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-14
    Description: by Michelle W. Antoine, Xiaoxia Zhu, Marianne Dieterich, Thomas Brandt, Sarath Vijayakumar, Nicholas McKeehan, Joseph C. Arezzo, R. Suzanne Zukin, David A. Borkholder, Sherri M. Jones, Robert D. Frisina, Jean M. Hébert How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission. By unilaterally targeting striatal activity with an antagonist of extracellular signal-regulated kinase (ERK), a downstream integrator of striatal neurotransmitter signaling, we can reverse or exaggerate rotational preference in these mice. By surgically biasing vestibular failure to one ear, we can dictate the direction of motor preference, illustrating the influence of uneven vestibular failure in establishing the outward asymmetries in motor preference. The inner ear–induced striatal asymmetries identified here intersect with non–ear-induced asymmetries previously linked to lateralized motor behavior across species and suggest that aspects of left–right brain function in mammals can be ontogenetically influenced by inner ear input. Consistent with inner ear input contributing to motor asymmetry, we also show that, in humans with normal ear function, the motor-dominant hemisphere, measured as handedness, is ipsilateral to the ear with weaker vestibular input.
    Print ISSN: 1544-9173
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  • 38
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    Publication Date: 2018-03-14
    Description: by Xiaolin Xu, Gita D. Mishra, Annette J. Dobson, Mark Jones Background The prevalence of diabetes, heart disease, and stroke multimorbidity (co-occurrence of two or three of these conditions) has increased rapidly. Little is known about how the three conditions progress from one to another sequentially through the life course. We aimed to delineate this progression in middle-aged women and to determine the roles of common risk factors in the accumulation of diabetes, heart disease, and stroke multimorbidity. Methods and findings We used data from 13,714 women aged 45–50 years without a history of any of the three conditions. They were participants in the Australian Longitudinal Study on Women's Health (ALSWH), enrolled in 1996, and surveyed approximately every 3 years to 2016. We characterized the longitudinal progression of the three conditions and multimorbidity. We estimated the accumulation of multimorbidity over 20 years of follow-up and investigated their association with both baseline and time-varying predictors (sociodemographic factors, lifestyle factors, and other chronic conditions).Over 20 years, 2,511 (18.3%) of the women progressed to at least one condition, of whom 1,420 (56.6%) had diabetes, 1,277 (50.9%) had heart disease, and 308 (12.3%) had stroke; 423 (16.8%) had two or three of these conditions. Over a 3-year period, the age-adjusted odds of two or more conditions was approximately twice that of developing one new condition compared to women who did not develop any new conditions. For example, the odds for developing one new condition between Surveys 7 and 8 were 2.29 (95% confidence interval [CI], 1.93–2.72), whereas the odds for developing two or more conditions was 6.51 (95% CI, 3.95–10.75). The onset of stroke was more strongly associated with the progression to the other conditions (i.e., 23.4% [95% CI, 16.3%–32.2%] of women after first onset of stroke progressed to other conditions, whereas the percentages for diabetes and heart disease were 9.9% [95% CI, 7.9%–12.4%] and 11.4% [95% CI, 9.1%–14.4%], respectively). Being separated, divorced, or widowed; being born outside Australia; having difficulty managing on their available income; being overweight or obese; having hypertension; being physically inactive; being a current smoker; and having prior chronic conditions (i.e., mental disorders, asthma, cancer, osteoporosis, and arthritis) were significantly associated with increased odds of accumulation of diabetes, heart disease, and stroke multimorbidity. The main limitations of this study were the use of self-reported data and the low number of events. Conclusions Stroke was associated with increased risk of progression to diabetes or heart disease. Social inequality, obesity, hypertension, physical inactivity, smoking, or having other chronic conditions were also significantly associated with increased odds of accumulating multimorbidity. Our findings highlight the importance of awareness of the role of diabetes, heart disease, and stroke multimorbidity among middle-aged women for clinicians and health-promotion agencies.
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
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  • 39
    Publication Date: 2018-03-14
    Description: by Edeltraud J. Lenk, William K. Redekop, Marianne Luyendijk, Christopher Fitzpatrick, Louis Niessen, Wilma A. Stolk, Fabrizio Tediosi, Adriana J. Rijnsburger, Roel Bakker, Jan A. C. Hontelez, Jan H. Richardus, Julie Jacobson, Epke A. Le Rutte, Sake J. de Vlas, Johan L. Severens Background The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). Methods A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011–2020 and 2021–2030. The ideal scenario in which the WHO’s 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. Results The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 –I$ 34.0) billion in 2011–2020 and I$ 35.9 (I$ 25.0 –I$ 51.9) billion in 2021–2030 (2.5 th and 97.5 th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 –US$ 15.7) and US$ 16.6 billion (US$ 11.6 –US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. Conclusions We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world’s prosperity more equitably and reduce inequity.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 40
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    Publication Date: 2018-03-14
    Description: by Dong-Xu Han, Yue Xiao, Chang-Jiang Wang, Hao Jiang, Yan Gao, Bao Yuan, Jia-Bao Zhang Follicle-stimulating hormone (FSH) has key roles in animal reproduction, including spermatogenesis and ovarian maturation. Many factors influence FSH secretion. However, despite the broad functions of microRNAs (miRNAs) via the regulation of target genes, little is known about their roles in FSH secretion. Our previous results suggested that miR-186-5p targets the 3′ UTR of FSHb ; therefore, we examined whether miR-186-5p could regulate FSH secretion in rat anterior adenohypophyseal cells. miR-186-5p was transfected into rat anterior pituitary cells. The expression of FSHb and the secretion of FSH were examined by RT-qPCR and ELISA. A miR-186-5p mimic decreased the expression of FSHb compared with expression in the control group and decreased FSH secretion. In contrast, both the mRNA levels and secretion of FSH increased in response to miR-186-5p inhibitors. Our results demonstrate that miR-186-5p regulates FSH secretion by directly targeting the FSHb 3′ UTR, providing additional functional evidence for the importance of miRNAs in the regulation of animal reproduction.
    Electronic ISSN: 1932-6203
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  • 41
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-14
    Description: by Igor Mozetič, Luis Torgo, Vitor Cerqueira, Jasmina Smailović Social media are becoming an increasingly important source of information about the public mood regarding issues such as elections, Brexit, stock market, etc. In this paper we focus on sentiment classification of Twitter data. Construction of sentiment classifiers is a standard text mining task, but here we address the question of how to properly evaluate them as there is no settled way to do so. Sentiment classes are ordered and unbalanced, and Twitter produces a stream of time-ordered data. The problem we address concerns the procedures used to obtain reliable estimates of performance measures, and whether the temporal ordering of the training and test data matters. We collected a large set of 1.5 million tweets in 13 European languages. We created 138 sentiment models and out-of-sample datasets, which are used as a gold standard for evaluations. The corresponding 138 in-sample datasets are used to empirically compare six different estimation procedures: three variants of cross-validation, and three variants of sequential validation (where test set always follows the training set). We find no significant difference between the best cross-validation and sequential validation. However, we observe that all cross-validation variants tend to overestimate the performance, while the sequential methods tend to underestimate it. Standard cross-validation with random selection of examples is significantly worse than the blocked cross-validation, and should not be used to evaluate classifiers in time-ordered data scenarios.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 42
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-14
    Description: by Nicolaia Iaffaldano, Michele Di Iorio, Luisa Mannina, Gianluca Paventi, Maria Pina Rosato, Silvia Cerolini, Anatoly P. Sobolev Metabolic profile of fresh turkey spermatozoa at three different reproductive period ages, namely 32, 44 and 56 weeks, was monitored by Nuclear Magnetic Resonance (NMR) spectroscopy and correlated to sperm quality parameters. The age-related decrease in sperm quality as indicated by reduction of sperm concentration, sperm mobility and osmotic tolerance was associated to variation in the level of specific water-soluble and liposoluble metabolites. In particular, the highest levels of isoleucine, phenylalanine, leucine, tyrosine and valine were found at 32 weeks of age, whereas aspartate, lactate, creatine, carnitine, acetylcarnitine levels increased during the ageing. Lipid composition also changed during the ageing: diunsaturated fatty acids level increased from 32 to 56 weeks of age, whereas a reduction of polyunsaturated fatty acids content was observed at 56 weeks. The untargeted approach attempts to give a wider picture of metabolic changes occurring in ageing suggesting that the reduction of sperm quality could be due to a progressive deficiency in mitochondrial energy producing systems, as also prompted by the negative correlation found between sperm mobility and the increase in certain mitochondrial metabolites.
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  • 43
    Publication Date: 2018-03-14
    Description: by Alison M. Earley, Cameron T. Dixon, Celia E. Shiau FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs ( foxq1a and foxq1b ) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish. Using a combination of molecular, cellular, and embryological approaches, we characterized single and double foxq1a bcz11 and foxq1b bcz18 mutants. This study provides the first genetic mutant analyses of zebrafish foxq1a and foxq1b . Interestingly, we found that foxq1a , but not foxq1b , was transcriptionally regulated during a bacterial response, while the expression of foxq1a was detected in sorted macrophages and upregulated in foxq1a -deficient mutants. However, the transcriptional response to E . coli challenge of foxq1a and foxq1b mutants was not significantly different from that of their wildtype control siblings. Our data shows that foxq1a may have a role in modulating bacterial response, while both foxq1a and foxq1b are not required for the development of macrophages, neutrophils, and microglia. Considering the implicated role of FOXQ1 in a vast number of cancers and biological processes, the foxq1a and foxq1b null mutants from this study provide useful genetic models to further investigate FOXQ1 functions.
    Electronic ISSN: 1932-6203
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  • 44
    Publication Date: 2018-03-14
    Description: by Hiroyuki Motoyama, Akihiro Tamori, Shoji Kubo, Sawako Uchida-Kobayashi, Shigekazu Takemura, Shogo Tanaka, Satoko Ohfuji, Yuga Teranishi, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Hiroyasu Morikawa, Masaru Enomoto, Yoshiki Murakami, Norifumi Kawada Background Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients. Methods Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively). We compared the clinical and histopathological factors between the two groups. Immunohistochemistry for Cytoglobin (CYGB) and α smooth muscle actin (α-SMA) was also performed. Results At baseline, prior to initiating the IFN-based therapy, there were significant differences between the SVR-non-HCC and SVR-HCC groups in the male gender, HBc antibody positivity, prothrombin activity, and histological inflammatory grade. Histopathological evaluation, using the new Inuyama classification system, revealed an improvement in the inflammatory grade, from 2.1 ± 0.6 to 1.0 ± 0.6 (p 〈 0.0001), whereas the fibrosis stage remained unchanged, from 2.3 ± 0.9 to 2.0 ± 1.2 (p = 0.2749), during the 97 ± 72-month observation period in the SVR-HCC group. Both the grade and stage scores were significantly improved in the SVR-non-HCC group. The area of collagen deposition, evaluated using Sirius red staining, showed a marked decrease, from 18.6 ± 7.6% to 7.7 ± 4.6%, in the SVR-non-HCC group, with no change in the SVR-HCC group. CYGB- and α-SMA-positive hepatic stellate cells (HSCs), indicative of the HSC activated phenotype, remained in the fibrotic tissue of livers among patients in the SVR-HCC group. Conclusion Stagnation of fibrosis regression is associated with a high risk for HCC after SVR. HSC activation may inhibit improvement in fibrosis after SVR and potentially contribute to hepatocarcinogenesis.
    Electronic ISSN: 1932-6203
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  • 45
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-14
    Description: by Hannah Crocker Cunningham, Kristi M. Cammack, Kristin E. Hales, Harvey C. Freetly, Amanda K. Lindholm-Perry Feed costs account for over 70% of the annual expenditures in cow/calf production. During the production year the cow uses nutrients to support conceptus growth, milk production, work (grazing and locomotion), and maintenance requirements. The majority of the nutrients are used to support maintenance. Substrate cycling has been identified as one of the major contributors toward energy expenditure associated with maintenance in mature cows. The objective of this study was to determine whether beef cows that differ in the efficiency of weight gain differ in the relative abundance of transcripts for metabolic regulation in adipose tissue. Mature beef cows were subjected to feed restriction followed by ad libitum feed. Adipose tissue from twelve cows with high (n = 6) and low (n = 6) gain based on growth performance during the ad libitum feeding period was evaluated for transcriptome expression differences. A total of 496 genes were differentially expressed and passed Bonferroni correction for the animals with greater gain between restriction and realimentation and 491 genes were differentially expressed among animals with lesser gains between feed restriction and realimentation. Of these two differentially expressed gene lists, 144 genes were common between animals with greater and those with lesser gain. Enriched biological processes included the TCA cycle, oxidative phosphorylation, respiratory electron transport chain and fatty acid metabolic processes. Specific to adipose tissue of low gaining animals was glycolysis and to high gain animals was coenzyme, steroid, cellular amino acid, nitrogen compound metabolic processes, and sensory perception. The oxidative phosphorylation, mitochondrial dysfunction and cholesterol biosynthesis pathways were commonly associated with the high gain animals between feed restriction and realimentation, as well as with the low gaining animals between the two time points. Unique to the high gaining animals were valine degradation and LPS/IL-1 mediated inhibition of RXR function pathways. In this discovery study, genes involved in lipid metabolism, mitochondrial respiration and oxidative phosphorylation pathways appear to be critical to mature cows during times of abundant feed after feed restriction.
    Electronic ISSN: 1932-6203
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  • 46
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-14
    Description: by Junho Lee, Hyuk-Jun Chang In this paper, explicit Model Predictive Control(MPC) is employed for automated lane-keeping systems. MPC has been regarded as the key to handle such constrained systems. However, the massive computational complexity of MPC, which employs online optimization, has been a major drawback that limits the range of its target application to relatively small and/or slow problems. Explicit MPC can reduce this computational burden using a multi-parametric quadratic programming technique(mp-QP). The control objective is to derive an optimal front steering wheel angle at each sampling time so that autonomous vehicles travel along desired paths, including straight, circular, and clothoid parts, at high entry speeds. In terms of the design of the proposed controller, a method of choosing weighting matrices in an optimization problem and the range of horizons for path-following control are described through simulations. For the verification of the proposed controller, simulation results obtained using other control methods such as MPC, Linear-Quadratic Regulator(LQR), and driver model are employed, and CarSim, which reflects the features of a vehicle more realistically than MATLAB/Simulink, is used for reliable demonstration.
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  • 47
    Publication Date: 2018-03-14
    Description: by Li Yang, Zhiming Zheng According to advancements in the wireless technologies, study of biometrics-based multi-server authenticated key agreement schemes has acquired a lot of momentum. Recently, Wang et al. presented a three-factor authentication protocol with key agreement and claimed that their scheme was resistant to several prominent attacks. Unfortunately, this paper indicates that their protocol is still vulnerable to the user impersonation attack, privileged insider attack and server spoofing attack. Furthermore, their protocol cannot provide the perfect forward secrecy. As a remedy of these aforementioned problems, we propose a biometrics-based authentication and key agreement scheme for multi-server environments. Compared with various related schemes, our protocol achieves the stronger security and provides more functionality properties. Besides, the proposed protocol shows the satisfactory performances in respect of storage requirement, communication overhead and computational cost. Thus, our protocol is suitable for expert systems and other multi-server architectures. Consequently, the proposed protocol is more appropriate in the distributed networks.
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  • 48
    Publication Date: 2018-03-16
    Description: by Núria Folguera-Blasco, Elisabet Cuyàs, Javier A. Menéndez, Tomás Alarcón Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers. The heterogeneity of epigenetic metabolites, which operates as regulator of the kinetic parameters promoting/preventing histone modifications, stochastically drives phenotypic variability. The ensemble of ER configurations reveals the occurrence of distinct epi-states within the ensemble. Whereas resilient states maintain large epigenetic barriers refractory to reprogramming cellular identity, plastic states lower these barriers, and increase the sensitivity to reprogramming. Moreover, fine-tuning of cofactor levels redirects plastic epigenetic states to re-enter epigenetic resilience, and vice versa. Our ensemble model agrees with a model of metabolism-responsive loss of epigenetic resilience as a cellular aging mechanism. Our findings support the notion that cellular aging, and its reversal, might result from stochastic translation of metabolic inputs into resilient/plastic cell states via ER systems.
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  • 49
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-16
    Print ISSN: 1553-734X
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  • 50
    Publication Date: 2018-03-16
    Description: by Andrea Cristine Koishi, Andréia Akemi Suzukawa, Camila Zanluca, Daria Elena Camacho, Guillermo Comach, Claudia Nunes Duarte dos Santos Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV). In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported. Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms. After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed. Plaque reduction neutralization test (PRNT) is indicated to confirm positive samples for being more specific, however it is laborious intensive and time consuming, representing a major bottleneck for patient diagnosis. To overcome this limitation, we developed a high-throughput image-based fluorescent neutralization test for ZIKV infection by serological detection. Using 226 human specimens, we showed that the new test presented higher throughput than traditional PRNT, maintaining the correlation between results. Furthermore, when tested with dengue virus samples, it showed 50.53% less cross reactivity than MAC-ELISA. This fluorescent neutralization test could be used for clinical diagnosis confirmation of ZIKV infection, as well as for vaccine clinical trials and seroprevalence studies.
    Print ISSN: 1935-2727
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  • 51
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-16
    Description: by Vanesa Alende-Castro, Cristina Macía-Rodríguez, Ignacio Novo-Veleiro, Xana García-Fernández, Mercedes Treviño-Castellano, Sergio Rodríguez-Fernández, Arturo González-Quintela Background Forms of presentation of Q fever vary widely across Spain, with differences between the north and south. In the absence of reported case series from Galicia (north-west Spain), this study sought to describe a Q-fever case series in this region for the first time, and conduct a systematic review to analyse all available data on the disease in Spain. Methods Patients with positive serum antibodies to Coxiella burnetii from a single institution over a 5-year period (January 2011-December 2015) were included. Patients with phase II titres above 1/128 (or documented seroconversion) and compatible clinical criterial were considered as having Q fever. Patients with clinical suspicion of chronic Q-fever and IgG antibodies to phase I-antigen of over 1/1024, or persistently high levels six months after treatment were considered to be cases of probable chronic Q-fever. Systematic review : We conducted a search of the Pubmed/Medline database using the terms: Q Fever OR Coxiella burnetii AND Spain . Our search yielded a total of 318 studies: 244 were excluded because they failed to match the main criteria, and 41 were discarded due to methodological problems, incomplete information or duplication. Finally, 33 studies were included. Results A total of 155 patients, all of them from Galicia, with positive serological determination were located during the study period; 116 (75%) were deemed to be serologically positive patients without Q fever and the remaining 39 (25%) were diagnosed with Q fever. A potential exposure risk was found in 2 patients (5%). The most frequent form of presentation was pneumonia (87%), followed by isolated fever (5%), diarrhoea (5%) and endocarditis (3%). The main symptoms were headache (100%), cough (77%) and fever (69%). A trend to a paucisymptomatic illness was observed in women. Hospital admission was required in 37 cases, and 6 patients died while in hospital. Only 2 patients developed chronic Q-fever. Systematic review : Most cases were sporadic, mainly presented during the winter and spring, as pneumonia in 37%, hepatitis in 31% and isolated fever in 29.6% of patients. In the north of Spain, 71% of patients had pneumonia, 13.2% isolated fever and 13% hepatitis. In the central and southern areas, isolated fever was the most frequent form of presentation (40%), followed by hepatitis (38.4%) and pneumonia (17.6%). Only 31.7% of patients reported risk factors, and an urban-environment was the most frequent place of origin. Overall mortality was 0.9%, and the percentage of patients with chronic forms of Q-fever was 2%. Conclusions This is the first study to report on a Q-fever case series in Galicia. It shows that in this region, the disease affects the elderly population -even in the absence of risk factors- and is linked to a higher mortality than reported by previous studies. While pneumonia is the most frequent form of presentation in the north of the country, isolated fever and hepatitis tend to be more frequent in the central and southern areas. In Spain, 32% of Q-fever cases do not report contact with traditional risk factors, and around 58% live in urban areas.
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  • 52
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    Publication Date: 2018-03-16
    Description: by Arran Hamlet, Kévin Jean, William Perea, Sergio Yactayo, Joseph Biey, Maria Van Kerkhove, Neil Ferguson, Tini Garske Background Yellow fever virus (YFV) is a vector-borne flavivirus endemic to Africa and Latin America. Ninety per cent of the global burden occurs in Africa where it is primarily transmitted by Aedes spp , with Aedes aegypti the main vector for urban yellow fever (YF). Mosquito life cycle and viral replication in the mosquito are heavily dependent on climate, particularly temperature and rainfall. We aimed to assess whether seasonal variations in climatic factors are associated with the seasonality of YF reports. Methodology/Principal findings We constructed a temperature suitability index for YFV transmission, capturing the temperature dependence of mosquito behaviour and viral replication within the mosquito. We then fitted a series of multilevel logistic regression models to a dataset of YF reports across Africa, considering location and seasonality of occurrence for seasonal models, against the temperature suitability index, rainfall and the Enhanced Vegetation Index (EVI) as covariates alongside further demographic indicators. Model fit was assessed by the Area Under the Curve (AUC), and models were ranked by Akaike’s Information Criterion which was used to weight model outputs to create combined model predictions. The seasonal model accurately captured both the geographic and temporal heterogeneities in YF transmission (AUC = 0.81), and did not perform significantly worse than the annual model which only captured the geographic distribution. The interaction between temperature suitability and rainfall accounted for much of the occurrence of YF, which offers a statistical explanation for the spatio-temporal variability in transmission. Conclusions/Significance The description of seasonality offers an explanation for heterogeneities in the West-East YF burden across Africa. Annual climatic variables may indicate a transmission suitability not always reflected in seasonal interactions. This finding, in conjunction with forecasted data, could highlight areas of increased transmission and provide insights into the occurrence of large outbreaks, such as those seen in Angola, the Democratic Republic of the Congo and Brazil.
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  • 53
    Publication Date: 2018-03-16
    Description: by Jesse C. Miles, Jessica Hua, Maria S. Sepulveda, Christian H. Krupke, Jason T. Hoverman
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 54
    Publication Date: 2018-03-16
    Description: by Yan Li, Zhirong Zhang, Junbo Yang, Guanghui Lv Fritillaria spp. constitute important traditional Chinese medicinal plants. Xinjiang is one of two diversity hotspots in China in which eight Fritillaria species occur, two of which are endemic to the region. Furthermore, the phylogenetic relationships of Xinjiang Fritillaria species (including F . yuminensis ) within the genus are unclear. In the present study, we sequenced the chloroplast (cp) genomes of seven Fritillaria species in Xinjiang using the Illumina HiSeq platform, with the aim of assessing the global structural patterns of the seven cp genomes and identifying highly variable cp DNA sequences. These were compared to previously sequenced Fritillaria cp genomes. Phylogenetic analysis was then used to evaluate the relationships of the Xinjiang species and assess the evolution of an undivided stigma. The seven cp genomes ranged from 151,764 to 152,112 bp, presenting a traditional quadripartite structure. The gene order and gene content of the seven cp genomes were identical. A comparison of the 13 cp genomes indicated that the structure is highly conserved. Ten highly divergent regions were identified that could be valuable in phylogenetic and population genetic studies. The phylogenetic relationships of the 13 Fritillaria species inferred from the protein-coding genes, large single-copy, small single-copy, and inverted repeat regions were identical and highly resolved. The phylogenetic relationships of the species corresponded with their geographic distribution patterns, in that the north group (consisting of eight species from Xinjiang and Heilongjiang in North China) and the south group (including six species from South China) were basically divided at 40°N. Species with an undivided stigma were not monophyletic, suggesting that this trait might have evolved several times in the genus.
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  • 55
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    Publication Date: 2018-03-16
    Description: by Nancy A. Scott, Taryn Vian, Jeanette L. Kaiser, Thandiwe Ngoma, Kaluba Mataka, Elizabeth G. Henry, Godfrey Biemba, Mary Nambao, Davidson H. Hamer Background The WHO recommends maternity waiting homes (MWH) as one intervention to improve maternal and newborn health. However, persistent structural, cultural and financial barriers in their design and implementation have resulted in mixed success in both their uptake and utilization. Guidance is needed on how to design a MWH intervention that is acceptable and sustainable. Using formative research and guided by a sustainability framework for health programs, we systematically collected data from key stakeholders and potential users in order to design a MWH intervention in Zambia that could overcome multi-dimensional barriers to accessing facility delivery, be acceptable to the community and be financially and operationally sustainable. Methods and findings We used a concurrent triangulation study design and mixed methods. We used free listing to gather input from a total of 167 randomly sampled women who were pregnant or had a child under the age of two (n = 59), men with a child under the age of two (n = 53), and community elders (n = 55) living in the catchment areas of four rural health facilities in Zambia. We conducted 17 focus group discussions (n = 135) among a purposive sample of pregnant women (n = 33), mothers-in-law (n = 32), traditional birth attendants or community maternal health promoters (n = 38), and men with a child under two (n = 32). We administered 38 semi-structured interviews with key informants who were identified by free list respondents as having a stake in the condition and use of MWHs. Lastly, we projected fixed and variable recurrent costs for operating a MWH.Respondents most frequently mentioned distance, roads, transport, and the quality of MWHs and health facilities as the major problems facing pregnant women in their communities. They also cited inadequate advanced planning for delivery and the lack of access to delivery supplies and baby clothes as other problems. Respondents identified the main problems of MWHs specifically as over-crowding, poor infrastructure, lack of amenities, safety concerns, and cultural issues. To support operational sustainability, community members were willing to participate on oversight committees and contribute labor. The annual fixed recurrent cost per 10-bed MWH was estimated as USD543, though providing food and charcoal added another $3,000USD. Respondents identified water pumps, an agriculture shop, a shop for baby clothes and general goods, and grinding mills as needs in their communities that could potentially be linked with an MWH for financial sustainability. Conclusions Findings informed the development of an intervention model for renovating existing MWH or constructing new MWH that meets community standards of safety, comfort and services offered and is aligned with government policies related to facility construction, ownership, and access to health services. The basic strategies of the new MWH model include improving community acceptability, strengthening governance and accountability, and building upon existing efforts to foster financial and operational sustainability. The proposed model addresses the problems cited by our respondents and challenges to MWHs identified by in previous studies and elicits opportunities for social enterprises that could serve the dual purpose of meeting a community need and generating revenue for the MWH.
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  • 56
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    Publication Date: 2018-03-17
    Description: by Yani Zhao, Pawel Dabrowski-Tumanski, Szymon Niewieczerzal, Joanna I. Sulkowska The folding of proteins with a complex knot is still an unresolved question. Based on representative members of Ubiquitin C-terminal Hydrolases (UCHs) that contain the 5 2 knot in the native state, we explain how UCHs are able to unfold and refold in vitro reversibly within the structure-based model. In particular, we identify two, topologically different folding/unfolding pathways and corroborate our results with experiment, recreating the chevron plot. We show that confinement effect of chaperonin or weak crowding greatly facilitates folding, simultaneously slowing down the unfolding process of UCHs, compared with bulk conditions. Finally, we analyze the existence of knots in the denaturated state of UCHs. The results of the work show that the crowded environment of the cell should have a positive effect on the kinetics of complex knotted proteins, especially when proteins with deeper knots are found in this family.
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  • 57
    Publication Date: 2018-03-17
    Description: by Manus Carey, Emily Donaldson, Antonio J. Signes-Pastor, Andrew A. Meharg There has been an increasing realisation that young infants are exposed to elevated concentrations of the carcinogen inorganic arsenic, relative to adults. This is because many infant food products are rice based, and rice is ~10-fold elevated in inorganic arsenic compared to most other foods. The European Commission (EC) has acted on this concern setting stricter standards for infants, 100 μg of inorganic arsenic per kg of food (100 μg/kg), as compared to adults (200 μg/kg), for rice based foods, a law that was brought into place in 1 st January 2016. Here we investigate how this law has impacted on inorganic arsenic in baby food products in the UK market, and compare the findings to previous baby food surveys taken before and just after the law came into place. We find that for a wide range of UK infant products that the new regulations are being adhered to, with all samples surveyed, being under 100 μg/kg inorganic arsenic. The prevalence of pure rice products had decreased in the UK, and there appears to be careful sourcing of the rice used in these products to ensure conformity with regulations. There has been an increased presence of mixed cereal products, with rice and maize as the main ingredient, appearing on the UK market, with varying rice contents for infant porridges, cakes and mueslis, with the latter being a relatively innovative product for infant foods. There was a highly significant correlation (P
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  • 58
    Publication Date: 2018-03-17
    Description: by Davina Gale, Andrew R. J. Lawson, Karen Howarth, Mikidache Madi, Bradley Durham, Sarah Smalley, John Calaway, Shannon Blais, Greg Jones, James Clark, Peter Dimitrov, Michelle Pugh, Samuel Woodhouse, Michael Epstein, Ana Fernandez-Gonzalez, Alexandra S. Whale, Jim F. Huggett, Carole A. Foy, Gerwyn M. Jones, Hadas Raveh-Amit, Karin Schmitt, Alison Devonshire, Emma Green, Tim Forshew, Vincent Plagnol, Nitzan Rosenfeld Introduction Detection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic and predictive tool in cancer patient care. A growing number of gene targets have been identified as diagnostic or actionable, requiring the development of reliable technology that provides analysis of multiple genes in parallel. We have developed the InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for the identification of clinically-relevant somatic alterations at low frequency in ctDNA across a panel of 35 cancer-related genes. Materials and methods We present analytical validation of the eTAm-Seq technology across two laboratories to determine the reproducibility of mutation identification. We assess the quantitative performance of eTAm-Seq technology for analysis of single nucleotide variants in clinically-relevant genes as compared to digital PCR (dPCR), using both established DNA standards and novel full-process control material. Results The assay detected mutant alleles down to 0.02% AF, with high per-base specificity of 99.9997%. Across two laboratories, analysis of samples with optimal amount of DNA detected 94% mutations at 0.25%-0.33% allele fraction (AF), with 90% of mutations detected for samples with lower amounts of input DNA. Conclusions These studies demonstrate that eTAm-Seq technology is a robust and reproducible technology for the identification and quantification of somatic mutations in circulating tumor DNA, and support its use in clinical applications for precision medicine.
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  • 59
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    Publication Date: 2018-03-17
    Description: by Donghuan Liu, Jing Zhang High-temperature thermal contact resistance (TCR) plays an important role in heat-pipe-cooled thermal protection structures due to the existence of contact interface between the embedded heat pipe and the heat resistive structure, and the reduction mechanism of thermal contact resistance is of special interests in the design of such structures. The present paper proposed a finite element model of the high-temperature thermal contact resistance based on the multi-point contact model with the consideration of temperature-dependent material properties, heat radiation through the cavities at the interface and the effect of thermal interface material (TIM), and the geometry parameters of the finite element model are determined by simple surface roughness test and experimental data fitting. The experimental results of high-temperature thermal contact resistance between superalloy GH600 and C/C composite material are employed to validate the present finite element model. The effect of the crucial parameters on the thermal contact resistance with and without TIM are also investigated with the proposed finite element model.
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  • 60
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-17
    Description: by Sangrok Jin, Jeongae Bak, Jongwon Kim, TaeWon Seo, Hwa Soo Kim This paper presents a switching PD-based sliding mode control (PD-SMC) method for the 6-degree-of-freedom (DOF) hovering motion of the underwater robot with tilting thrusters. Four thrusters of robot can be tilted simultaneously in the horizontal and vertical directions, and the 6-DOF motion is achieved by switching between two thruster configurations. Therefore, the tilting speed of thruster becomes the most essential parameter to determine the stability of hovering motion. Even though the previous PD control ensures stable hovering motion within a certain ranges of tilting speed, a PD-SMC is suggested in this paper by combining PD control with sliding mode control in order to achieve acceptable hovering performance even at the much lower tilting speeds. Also, the sign function in the sliding mode control is replaced by a sigmoid function to reduce undesired chattering. Simulations show that while PD control is effective only for tilting duration of 600 ms, the PD-based sliding mode control can guarantee the stable hovering motion of underwater robot even for the tilting duration of up to 1500 ms. Extensive experimental results confirm the hovering performance of the proposed PD-SMC method is much superior to that of PD method for much larger tilting durations.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 61
    Publication Date: 2018-03-17
    Description: by Sofía. I. Deperi, Martín. E. Tagliotti, M. Cecilia Bedogni, Norma C. Manrique-Carpintero, Joseph Coombs, Ruofang Zhang, David Douches, Marcelo. A. Huarte The reported narrow genetic base of cultivated potato ( Solanum tuberosum ) can be expanded by the introgression of many related species with large genetic diversity. The analysis of the genetic structure of a potato population is important to broaden the genetic base of breeding programs by the identification of different genetic pools. A panel composed by 231 diverse genotypes was characterized using single nucleotide polymorphism (SNP) markers of the Illumina Infinium Potato SNP Array V2 to identify population structure and assess genetic diversity using discriminant analysis of principal components (DAPC) and pedigree analysis. Results revealed the presence of five clusters within the populations differentiated principally by ploidy, taxonomy, origin and breeding program. The information obtained in this work could be readily used as a guide for parental introduction in new breeding programs that want to maximize variability by combination of contrasting variability sources such as those presented here.
    Electronic ISSN: 1932-6203
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  • 62
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-17
    Description: by Laurent Oxusoff, Pascal Préa, Yvan Perez Investigating how recombination might modify gene order during the evolution has become a routine part of mitochondrial genome analysis. A new method of genomic maps analysis based on formal logic is described. The purpose of this method is to 1) use mitochondrial gene order of current taxa as datasets 2) calculate rearrangements between all mitochondrial gene orders and 3) reconstruct phylogenetic relationships according to these calculated rearrangements within a tree under the assumption of maximum parsimony. Unlike existing methods mainly based on the probabilistic approach, the main strength of this new approach is that it calculates all the exact tree solutions with completeness and provides logical consequences as highly robust results. Moreover, this method infers all possible hypothetical ancestors and reconstructs character states for all internal nodes of the trees. We started by testing our method using the deuterostomes as a study case. Then, with sponges as an outgroup, we investigated the evolutionary history of mitochondrial genomes of 47 bilaterian phyla and emphasised the peculiar case of chaetognaths. This pilot work showed that the use of formal logic in a hypothetico-deductive background such as phylogeny (where experimental testing of hypotheses is impossible) is very promising to explore mitochondrial gene order in deuterostomes and should be applied to many other bilaterian clades.
    Electronic ISSN: 1932-6203
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  • 63
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-17
    Description: by Lily Wei Chen, Chien-Jung Huang, Wen-Hui Tu, Chia-Ju Lu, Yi-Chen Sun, Szu-Yuan Lin, Wei-Li Chen Purpose To evaluate whether lyophilized human platelet lysate (HPL) powder can preserve the growth factor concentrations and epitheliotrophic properties of liquid HPL, and potentially be used as a clinically-friendly treatment option. Methods Two commercialized liquid HPLs, UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were obtained and converted to lyophilized powder. After redissolution, lyophilized powder HPLs were compared with liquid HPLs, as well as human peripheral serum (HPS) and fetal bovine serum (FBS) in liquid or redissolved lyophilized powder forms. Concentrations of epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-AB (PDGF-AB) and platelet-derived growth factor-BB (PDGF-BB) were evaluated by enzyme-linked immunosorbent assay (ELISA). Human corneal epithelial cell line was incubated with the blood derivatives and evaluated for cell migration with scratch-induced directional wounding and proliferation with MTS assays. Cell differentiation was examined by transepithelial electrical resistance (TEER). Fluorescein staining and in vivo confocal microscopy were used to evaluate in vivo corneal epithelial wound healing in Sprague-Dawley rats that underwent corneal debridement and topical application of liquid and redissolved powder HPLs. Results Liquid form and redissolved lyophilized powder form HPLs had similar concentrations of EGF, TGF-β1, PDGF-AB and PDGF-BB. In vitro experiments on cell migration, proliferation and differentiation and rat models on wound healing demonstrated no significant difference between the liquid and redissolved lyophilized powder forms for HPLs, HPS and FBS. In vivo confocal microscopy revealed similar wound healing process at different layers of cornea after corneal epithelial debridement between liquid form and redissolved lyophilized power form of HPLs. Conclusions The redissolved lyophilized powder form of both commercialized HPLs showed similar growth factor concentrations and corneal epitheliotrophic abilities compared to the liquid form. Results suggest that the properties of liquid HPLs can be retained despite lyophilization and that lyophilized HPLs can be a treatment option for corneal epithelial disorders.
    Electronic ISSN: 1932-6203
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  • 64
    Publication Date: 2018-03-17
    Description: by Tatsuya Soeno, Tomoharu Mochizuki, Osamu Tanifuji, Hiroshi Koga, Takayuki Murayama, Hiroki Hijikata, Yuki Takahashi, Naoto Endo Introduction Instability after total knee arthroplasty is a critical problem. The purpose of this study was to clarify the stability of implanted knees during walking by comparing differences in dynamic instability during knee acceleration between individuals with or without previously experienced subjective instability, as measured by self-reported questionnaire. Materials and methods We examined 92 knees with medial pivot implants. Mean patient age and follow-up duration were 78.4 years and 32.8 months, respectively. An accelerometer was used to investigate the accelerations along three axes; that is, vertical (VT), mediolateral (ML), and anteroposterior (AP) directions in 3-dimensional (3D) space. The analysis in the stance phase and gait cycle was performed by: (1) root mean square (RMS) values of acceleration and (2) frequency domain analysis using fast Fourier transformation (FFT). A self-reported knee instability score was used for the subjective feeling of instability. Results A total of 76 knees did not feel unstable (group 0), but 16 knees felt unstable (group 1) in patients during activities of daily living. Regarding the RMS, there were no differences in each direction between the groups. For FFT, the cumulative amplitude in the frequency 〈 30 Hz also showed no significant differences in all directions between the groups during the stance phase (VT, p = 0.335; ML, p = 0.219; AP, p = 0.523) or gait cycle (VT, p = 0.077; ML, p = 0.082; AP, p = 0.499). Discussion Gait analysis based on the acceleration data showed that there were no between-group differences in objective dynamic instability during acceleration of the knee, with or without reports of previously experienced subjective instability, as assessed by the self-reported questionnaire.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 65
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-17
    Description: by Ravi Prakash Saini, Venkat Raman, Gurusamy Dhandapani, Era Vaidya Malhotra, Rohini Sreevathsa, Polumetla Ananda Kumar, Tilak R. Sharma, Debasis Pattanayak The polyphagous insect-pest, Helicoverpa armigera , is a serious threat to a number of economically important crops. Chemical application and/or cultivation of Bt transgenic crops are the two strategies available now for insect-pest management. However, environmental pollution and long-term sustainability are major concerns against these two options. RNAi is now considered as a promising technology to complement Bt to tackle insect-pests menace. In this study, we report host-delivered silencing of HaAce1 gene, encoding the predominant isoform of H . armigera acetylcholinesterase, by an artificial microRNA, HaAce1 -amiR1. Arabidopsis pre-miRNA164b was modified by replacing miR164b/miR164b* sequences with HaAce1 -amiR1/ HaAce1 -amiR1* sequences. The recombinant HaAce1 -preamiRNA1 was put under the control of CaMV 35S promoter and NOS terminator of plant binary vector pBI121, and the resultant vector cassette was used for tobacco transformation. Two transgenic tobacco lines expressing HaAce1 -amiR1 was used for detached leaf insect feeding bioassays. Larval mortality of 25% and adult deformity of 20% were observed in transgenic treated insect group over that control tobacco treated insect group. The reduction in the steady-state level of HaAce1 mRNA was 70–80% in the defective adults compared to control. Our results demonstrate promise for host-delivered amiRNA-mediated silencing of HaAce1 gene for H . armigera management.
    Electronic ISSN: 1932-6203
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  • 66
    Publication Date: 2018-03-17
    Description: by Anatole Manzi, Jean Claude Mugunga, Hari S. Iyer, Hema Magge, Fulgence Nkikabahizi, Lisa R. Hirschhorn Background Integrated management of childhood illness (IMCI) can reduce under-5 morbidity and mortality in low-income settings. A program to strengthen IMCI practices through Mentorship and Enhanced Supervision at Health centers (MESH) was implemented in two rural districts in eastern Rwanda in 2010. Methods We estimated cost per improvement in quality of care as measured by the difference in correct diagnosis and correct treatment at baseline and 12 months of MESH. Costs of developing and implementing MESH were estimated in 2011 United States Dollars (USD) from the provider perspective using both top-down and bottom-up approaches, from programmatic financial records and site-level data. Improvement in quality of care attributed to MESH was measured through case management observations (n = 292 cases at baseline, 413 cases at 12 months), with outcomes from the intervention already published. Sensitivity analyses were conducted to assess uncertainty under different assumptions of quality of care and patient volume. Results The total annual cost of MESH was US$ 27,955.74 and the average cost added by MESH per IMCI patient was US$1.06. Salary and benefits accounted for the majority of total annual costs (US$22,400 /year). Improvements in quality of care after 12 months of MESH implementation cost US$2.95 per additional child correctly diagnosed and $5.30 per additional child correctly treated. Conclusions The incremental costs per additional child correctly diagnosed and child correctly treated suggest that MESH could be an affordable method for improving IMCI quality of care elsewhere in Rwanda and similar settings. Integrating MESH into existing supervision systems would further reduce costs, increasing potential for spread.
    Electronic ISSN: 1932-6203
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  • 67
    Publication Date: 2018-03-17
    Description: by Joseph D. Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F. Guimaraes, Darren A. N. Cook, Andrew Steven, Nico Van Rooijen, Judith E. Allen, Stephen J. Jenkins, Mark J. Taylor Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 68
    Publication Date: 2018-03-20
    Description: by Bruce Y. Lee, Sarah M. Bartsch, Laura Skrip, Daniel L. Hertenstein, Cameron M. Avelis, Martial Ndeffo-Mbah, Carla Tilchin, Eric O. Dumonteil, Alison Galvani Background The 2020 Sustainable Development goals call for 100% certified interruption or control of the three main forms of Chagas disease transmission in Latin America. However, how much will achieving these goals to varying degrees control Chagas disease; what is the potential impact of missing these goals and if they are achieved, what may be left? Methods We developed a compartmental simulation model that represents the triatomine, human host, and non-human host populations and vector-borne, congenital, and transfusional T . cruzi transmission between them in the domestic and peridomestic settings to evaluate the impact of limiting transmission in a 2,000 person virtual village in Yucatan, Mexico. Results Interruption of domestic vectorial transmission had the largest impact on T . cruzi transmission and prevalence in all populations. Most of the gains were achieved within the first few years. Controlling vectorial transmission resulted in a 46.1–83.0% relative reduction in the number of new acute Chagas cases for a 50–100% interruption in domestic vector-host contact. Only controlling congenital transmission led to a 2.4–8.1% (30–100% interruption) relative reduction in the total number of new acute cases and reducing only transfusional transmission led to a 0.1–0.3% (30–100% reduction). Stopping all three forms of transmission resulted in 0.5 total transmission events over five years (compared to 5.0 with no interruption); interrupting all forms by 30% resulted in 3.4 events over five years per 2,000 persons. Conclusions While reducing domestic vectorial, congenital, and transfusional transmission can successfully reduce transmission to humans (up to 82% in one year), achieving the 2020 goals would still result in 0.5 new acute cases per 2,000 over five years. Even if the goals are missed, major gains can be achieved within the first few years. Interrupting transmission should be combined with other efforts such as a vaccine or improved access to care, especially for the population of already infected individuals.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 69
    Publication Date: 2018-03-20
    Description: by Stephane Olindo, Severine Jeannin, Martine Saint-Vil, Aissatou Signate, Mireille Edimonana-Kaptue, Julien Joux, Harold Merle, Pascale Richard, Samuel Granjeaud, Philippe Cabre, Didier Smadja, Raymond Cesaire, Agnes Lezin Background Human T-lymphotropic virus type 1 (HTLV-1) has been discovered in 1980 and has been linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique over 25 years. Methods Martinique is a Caribbean French West Indies island deserved by a unique Neurology Department involved in HAM/TSP diagnosis and management. A registry has been set up since 1986 and patients diagnosed for a HAM/TSP were prospectively registered. Only patients with a definite HAM/TSP onset between 1986 and 2010 were included in the present study. The 25-year study time was stratified in five-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. Age-standardized rates were calculated using the direct method and the Martinique population census of 1990 as reference. Standardized incidence rate ratios with 95% CIs and P trends were assessed from simple Poisson regression models. Number of HTLV-1 infection among first-time blood donors was retrospectively collected from the central computer data system of the Martinique blood bank. The HTLV-1 seroprevalence into this population has been calculated for four 5-year periods between 1996 and 2015. Results Overall, 153 patients were identified (mean age at onset, 53+/-13.1 years; female:male ratio, 4:1). Crude HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986–1990, 1991–1995, 1996–2000, 2001–2005 and 2006–2010 periods were 10.01 (6.78–13.28), 13.02 (9.34–16.70), 11.54 (8.13–14.95), 4.27 (2.24–6.28) and 2.03 (0.62–3.43). Age-standardized 5-year incidence rates significantly decreased by 69% and 87% in 2001–2005 and 2006–2010 study periods. Patients characteristics did not differ regarding 1986–2000 and 2001–2010 onset periods. Between 1996–2000 and 2011–2015 study periods, the HTLV-1 seroprevalence significantly decreased by 63%. Conclusion Martinique faces a sudden and rapid decline of HAM/TSP incidence from 2001 in comparison to 1986–2000 periods. Reduction of HTLV-1 seroprevalence, that may result from transmission prevention strategy, could account for HAM/TSP incidence decrease.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 70
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-20
    Description: by Ali Akgul, Ayfer Akgul, Mark L. Lawrence, Attila Karsi Edwardsiella ictaluri is a Gram-negative facultative anaerobic rod and the causative agent of enteric septicemia of channel catfish (ESC), which is one of the most prevalent diseases of catfish, causing significant economic losses in the catfish industry. E . ictaluri is resistant to complement system and macrophage killing, which results in rapid systemic septicemia. However, mechanisms of E . ictaluri stress responses under conditions of host environment are not studied well. Therefore, in this work, we report E . ictaluri stress responses during hydrogen peroxide, low pH, and catfish serum stresses as well as during catfish invasion. E . ictaluri stress responses were characterized by identifying expression of 13 universal stress protein (USP) genes ( usp01 - usp13 ) and seven USP-interacting protein genes ( groEL , groES , dnaK , grpE , and clpB , grpE , relA ). Data indicated that three usp genes ( usp05 , usp07 , and usp13 ) were highly expressed in all stress conditions. Similarly, E . ictaluri heat shock proteins groEL , groES , dnaK , grpE , and clpB were highly expressed in oxidative stress. Also, E . ictaluri grpE and relA were highly expressed in catfish spleen and head kidney. These findings contribute to our understanding of stress response mechanisms in E . ictaluri stress response, and stress-related proteins that are essential for E . ictaluri could be potential targets for live attenuated vaccine development against ESC.
    Electronic ISSN: 1932-6203
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  • 71
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    Public Library of Science (PLoS)
    Publication Date: 2018-03-20
    Description: by Jennifer Palomo, Sabina Troccaz, Dominique Talabot-Ayer, Emiliana Rodriguez, Gaby Palmer The IL-1 cytokine family includes eleven members, among which Il-36α, β and γ, IL-36Ra and IL-38. The IL-36 cytokines are involved in the pathogenesis of psoriasis. IL-38 is also expressed in the skin and was previously proposed to act as an IL-36 antagonist. In this study, we thus examined expression and function of Il-38 in a mouse model of imiquimod (IMQ)-induced skin inflammation. Il-38 mRNA was detected in the epidermis and in primary mouse keratinocytes, but not in dermal fibroblasts. At the peak of IMQ-induced inflammation, skin Il-38 mRNA levels were reduced, whereas Il-36ra mRNA expression increased. The severity of IMQ-induced skin inflammation, as assessed by recording ear thickness and histological changes, was similar in Il-38 KO and WT littermate control mice, while, in contrast, Il-36ra-deficient mice displayed more severe skin pathology than their WT littermates. Il-38-deficiency had no impact on IMQ-induced expression of proinflammatory mediators in the skin in vivo , on the basal expression of various cytokines or chemokines by cultured primary keratinocytes and dermal fibroblasts in vitro , or on the response of these cells to Il-36β. Finally, after cessation of topical IMQ application, the resolution of skin inflammation was also not altered in Il-38 KO mice. In conclusion, Il-38-deficiency did not impact the development or resolution of IMQ-induced skin inflammation. Our observations further suggest that endogenous Il-38 does not exert Il-36 inhibitory activity in this model, or in cultured skin cells. A potential anti-inflammatory function of Il-38 in mouse skin thus still remains to be demonstrated.
    Electronic ISSN: 1932-6203
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  • 72
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    Publication Date: 2018-03-21
    Description: by Wei-Hsin Yuan, Anna Fen-Yau Li, Yi-Hong Chou, Hui-Chen Hsu, Ying-Yuan Chen Objective The purpose of this study was to determine clinical and ultrasonographic characteristics of male breast tumors. Methods The medical records of male patients with breast lesions were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. A total of 112 men (125 breast masses) with preoperative breast ultrasonography (US) were included (median age, 59.50 years; age range, 15–96 years). Data extracted included patient age, if the lesions were bilateral, palpable, and tender, and the presence of nipple discharge. Breast lesion features on static US images were reviewed by three experienced radiologists without knowledge of physical examination or pathology results, original breast US image interpretations, or surgical outcomes. The US features were documented according to the BI-RADS (Breast Imaging-Reporting and Data System) US lexicons. A forth radiologist compiled the data for analysis. Results Of the 125 breast masses, palpable tender lumps and bilateral synchronous masses were more likely to be benign than malignant (both, 100% vs 0%, P 〈 0.05). Advanced age and bloody discharge from nipples were common in malignant lesions (P
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  • 73
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    Publication Date: 2018-03-21
    Description: by Michael Leung, Nandita Perumal, Elnathan Mesfin, Aditi Krishna, Seungmi Yang, William Johnson, Diego G. Bassani, Daniel E. Roth Metrics to quantify child growth vary across studies of the developmental origins of health and disease. We conducted a scoping review of child growth studies in which length/height, weight or body mass index (BMI) was measured at ≥ 2 time points. From a 10% random sample of eligible studies published between Jan 2010-Jun 2016, and all eligible studies from Oct 2015-June 2016, we classified growth metrics based on author-assigned labels (e.g., ‘weight gain’) and a ‘content signature’, a numeric code that summarized the metric’s conceptual and statistical properties. Heterogeneity was assessed by the number of unique content signatures, and label-to-content concordance. In 122 studies, we found 40 unique metrics of childhood growth. The most common approach to quantifying growth in length, weight or BMI was the calculation of each child’s change in z-score. Label-to-content discordance was common due to distinct content signatures carrying the same label, and because of instances in which the same content signature was assigned multiple different labels. In conclusion, the numerous distinct growth metrics and the lack of specificity in the application of metric labels challenge the integration of data and inferences from studies investigating the determinants or consequences of variations in childhood growth.
    Electronic ISSN: 1932-6203
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  • 74
    Publication Date: 2018-03-21
    Description: by Cindy Wenke, Janina Pospiech, Tobias Reutter, Bettina Altmann, Uwe Truyen, Stephanie Speck Biosecurity is defined as the implementation of measures that reduce the risk of disease agents being introduced and/or spread. For pig production, several of these measures are routinely implemented (e.g. cleaning, disinfection, segregation). However, air as a potential vector of pathogens has long been disregarded. Filters for incoming and recirculating air were installed into an already existing ventilation plant at a fattening piggery (3,840 pigs at maximum) in Saxony, Germany. Over a period of three consecutive fattening periods, we evaluated various parameters including air quality indices, environmental and operating parameters, and pig performance. Animal data regarding respiratory diseases, presence of antibodies against influenza A viruses, PRRSV, and Actinobacillus pleuropneumoniae and lung health score at slaughter were recorded, additionally. There were no significant differences (p = 0.824) in total bacterial counts between barns with and without air filtration. Recirculating air filtration resulted in the lowest total dust concentration (0.12 mg/m 3 ) and lung health was best in animals from the barn equipped with recirculating air filtration modules. However, there was no difference in animal performance. Antibodies against all above mentioned pathogens were detected but mostly animals were already antibody-positive at re-stocking. We demonstrated that supply air filtration as well as recirculating air filtration technique can easily be implemented in an already existing ventilation system and that recirculating air filtration resulted in enhanced lung health compared to supply air-filtered and non-filtered barns. A more prominent effect might have been obtained in a breeding facility because of the longer life span of sows and a higher biosecurity level with air filtration as an add-on measure.
    Electronic ISSN: 1932-6203
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  • 75
    Publication Date: 2018-03-21
    Description: by Roberto Pizzolotto, Antonio Mazzei, Teresa Bonacci, Stefano Scalercio, Nino Iannotta, Pietro Brandmayr The impact of agricultural practices and soil management on the communities of arthropods living in the agricultural landscape is acknowledged as a critical issue by the literature, and it needs to be better investigated to improve the ecological sustainability of agriculture. In the present study, we aimed to study how soil management affect carabid species distribution in one of the most typical agroecosystem of the Mediterranean region, i.e. the olive grove. In South Italy olive plantations feature different types of soil management, from tillage to half- or full-cover cropping. Species distribution has been examined for a total of 10,189 individuals and 62 species collected from 17 sites. Notably from our analysis we have observed that three factors (climax vegetation, soil features and soil management) explained half of the data variability. The composition of species groupings mirrors both bioclimatic conditions (climax vegetation) and soil features, especially watering, while soil management affects the species distribution, with different intensity from site to site. Eleven species have been recognized as the most abundant in the different facets of the studied olive groves and consequently designated as characteristics of the olive agroecosystem. The species traits of the sampled species have been weighted for a compelling evaluation of the effects of agricultural management on biodiversity, showing uniform traits distribution when coping with the ecological factors that characterize the different plantation facets. We have found that carabid beetles can be used as model organisms for studying the effects of agricultural practices. Our study suggests that the interaction of man-induced trasformation with the natural background of the olive agroecosystem may be difficult to disentangle, so that such complexity must be taken into account when carabid beetles are expected to provide an ecosystem service for good agricultural practices.
    Electronic ISSN: 1932-6203
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  • 76
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    Publication Date: 2018-03-21
    Description: by Jieun Yoon, Akihiro Kanamori, Keisuke Fujii, Hiroko Isoda, Tomohiro Okura Purpose Maslinic acid (MA) is a component derived from a natural olive-based extract known to have pharmacological functions that include suppressing inflammation. This study examined how MA, in conjunction with whole-body vibration training (WBVT), can improve knee and muscle function in elderly women with knee osteoarthritis (OA). Methods The study was a double-blinded, placebo-controlled, randomized intervention study that enrolled individuals with knee pain. Participants were 26 females aged 65–85 years with knee OA. They performed WBVT and ingested either 16.7 mg of MA or a placebo daily for 20 weeks. We compared the effect of WBVT with placebo (WBVT/P) and WBVT with MA (WBVT/MA) in participants with various degrees of knee OA (Kellgren and Lawrence (K-L) grade) using the Japanese Orthopaedic Association (JOA) score and isokinetic dynamometer measurements to evaluate knee and muscle function with two-way ANOVA. Results Based on the results of two-way ANOVA analysis of muscle function measurements, there was significant interaction (time × group) ( P = 0.03) in the “isokinetic extension peak torque” domain for severe OA (K-L grade ≥ 3). The simple main effect of time in the WBVT/MA group ( P = 0.04) contributed to this interaction. The JOA score for WBVT/MA supported the main effect of group as having a significant correlation in the “pain on walking” ( P = 0.04) and “range of motion” ( P 〈 0.01) domains. Participants with severe knee OA in the WBVT/MA group improved in these domains, whereas the WBVT/P group had few positive results. Conclusions Participants with severe OA who ingested MA in conjunction with WBVT improved their knee and muscle function. This study suggests that ingesting the anti-inflammatory supplement MA while participating in WBVT, elderly women can reduce knee OA and improve their knee muscle strength.
    Electronic ISSN: 1932-6203
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  • 77
    Publication Date: 2018-03-21
    Description: by Jung-Ah Lim, Jangsup Moon, Tae-Joon Kim, Jin-Sun Jun, Byeongsu Park, Jung-Ick Byun, Jun-Sang Sunwoo, Kyung-Il Park, Soon-Tae Lee, Keun-Hwa Jung, Ki-Young Jung, Manho Kim, Daejong Jeon, Kon Chu, Sang Kun Lee Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring. A seizure cluster was defined as the occurrence of one or more seizures per day for at least three consecutive days and at least five seizures during the cluster period. We analyzed the cluster duration, seizure-free period, cluster interval, and numbers of seizures within and outside the seizure clusters. The video-EEG monitoring began 84.5±33.7 days after the induction of SE and continued for 53.7±20.4 days. Every mouse displayed seizure clusters, and 97.0% of the seizures occurred within a cluster period. The seizure clusters were followed by long seizure-free periods of 16.3±6.8 days, showing a cyclic pattern. The SRSs also occurred in a grouped pattern within a day. We demonstrate that almost all seizures occur in clusters with a cyclic pattern in the chronic stage of a mouse pilocarpine-induced epilepsy model. The seizure-free periods between clusters were long. These findings should be considered when performing in vivo studies using this animal model. Furthermore, this model might be appropriate for studying the unrevealed mechanism of ictogenesis.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 78
    Publication Date: 2018-03-21
    Description: by Kyongje Sung, Barry Gordon Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 79
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