bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy
Authors: McAdams Ryan M. , Fleiss Bobbi , Traudt Christopher , Schwendimann Leslie , Snyder Jessica M. , Haynes Robin L. , Natarajan Niranjana , Gressens Pierre , Juul Sandra E.
Published: May 2017

Background: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. Methodology: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO). UCO animals were randomized to saline (n = 11), therapeutic hypothermia (TH; n = 6), or TH + erythropoietin (Epo; n = 8). Epo was given on days 1, 2, 3, and 7. Animals had serial developmental assessments and underwent magnetic resonance imaging with diffusion tensor imaging at 9 months of age followed by necropsy. Histology and immunohistochemical (IHC) staining of brain and brainstem sections were performed. Results: All UCO animals demonstrated and met the standard diagnostic criteria for human neonates with moderate-to-severe HIE. Four animals developed moderate-to-severe CP (3 UCO and 1 UCO + TH), 9 had mild CP (2 UCO, 3 UCO + TH, 3 UCO + TH + Epo, and 1 control), and 2 UCO animals died. None of the animals treated with TH + Epo died, had moderate-to-severe CP, or demonstrated signs of long-term neuropathological toxicity. Compared to animals grouped together as having no CP (no-CP; controls and mild CP only), animals with CP (moderate and severe) demonstrated decreased fractional anisotropy of multiple white-matter tracts including the corpus callosum and internal capsule, when using Tract-Based Spatial Statistics (TBSS). Animals with CP had decreased staining for cortical neurons and increased brainstem glial scarring compared to animals without CP. The cerebellar cell density of the internal granular layer and white matter was decreased in CP animals compared to that in control animals without CP. Conclusions/Significance: In this nonhuman primate HIE model, animals treated with TH + Epo had less brain pathology noted on TBSS and IHC staining, which supports the long-term safety of TH + Epo in the setting of HIE. Animals that developed CP showed white-matter changes noted on TBSS, subtle histopathological changes in both the white and gray matter, and brainstem injury that correlated with CP severity. This HIE model may lend itself to further study of the relationship between brainstem injury and CP.
Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta and Fetal Brain
Authors: Williams Monica , Zhang Zhi , Nance Elizabeth , Drewes Julia L. , Lesniak Wojciech G. , Singh Sarabdeep , Chugani Diane C. , Rangaramanujam Kannan , Graham David R. , Kannan Sujatha
Published: May 2017

Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain. We found that intrauterine endotoxin administration at gestational day 28 (G28) resulted in a significant upregulation of indoleamine 2,3-dioxygenase (IDO) in both the placenta and fetal brain at G29 (24 h after treatment). This endotoxin-mediated IDO induction was also associated with intense microglial activation, an increase in interferon gamma expression, and increases in kynurenine and the kynurenine pathway metabolites kynurenine acid and quinolinic acid, as well as a significant decrease in 5-hydroxyindole acetic acid (a precursor of serotonin) levels in the periventricular region of the fetal brain. These results indicate that maternal inflammation shunts tryptophan metabolism away from the serotonin to the kynurenine pathway, which may lead to excitotoxic injury along with impaired development of serotonin-mediated thalamocortical fibers in the newborn brain. These findings provide new targets for prevention and treatment of maternal inflammation-induced fetal and neonatal brain injury leading to neurodevelopmental disorders such as cerebral palsy and autism.
New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions
Authors: Li Jiang , Liu Lei , Rui Wenlong , Li Xiangyu , Xuan Dandan , Zheng Shucong , Yu Yiyun , Zhang Jiong , Kong Ning , Zhu Xiaoxia , Zou Hejian , Wan Weiguo , Xue Yu
Published: May 2017

Objectives: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). Methods: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. Results: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. Conclusion: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.
Fatty Acids Induce Stemness in the Stromal Cells of a CT26 Mouse Tumor Model
Authors: Kawahara Isao , Mori Takuya , Goto Kei , Fujii Kiyomu , Ohmori Hitoshi , Kishi Shingo , Fujiwara-Tani Rina , Kuniyasu Hiroki
Published: May 2017

The potential effects of 2 types of fatty acids on colorectal cancer (CRC) were assessed using cancer stromal cells. Linoleic acid (LA; C-18, n-6 unsaturated fatty acid) and elaidic acid (EA; C-18, trans acid), both known to affect colon carcinogenesis and cancer progression, were administered by gavage to BALB/c mice, which were inoculated with CT26 syngeneic colon cancer cells in the back. Both EA and LA treatments enhanced tumor growth and metastasis. EA and LA also increased the number of CD133-positive stromal cells in the tumor capsule. Importantly, those cancer cells at the tumor periphery, physically attached to CD133-positive stromal cells, also expressed CD133. These findings suggest that EA and LA might induce stemness in cancer cells through physical association and promote cancer metastasis.
Influence of Bovine Serum Lipids and Fetal Bovine Serum on the Expression of Cell Surface Markers in Cultured Bovine Preadipocytes
Authors: Sandhu Mansur A. , Jurek Sandra , Trappe Susanne , Kolisek Martin , Sponder Gerhard , Aschenbach Jörg R.
Published: May 2017

To establish the influence of fetal bovine serum (FBS) and bovine serum lipids (BSL) on cell differentiation marker expression, bovine adipose-derived stem cells from subcutaneous tissue were incubated for 14 days in 4 types of differentiation media containing 10% FBS and 10 µL/mL BSL (TRT-1), no FBS and 10 µL/mL of BSL (TRT-2), 10% FBS and no BSL (TRT-3), or no supplements (TRT-4). Cells were subjected to Nile red staining, immunocytochemistry (CD73, CD90, CD105, DLK1, FabP4), and quantitative real-time PCR (CD73, CD90, CD105, FabP4). The number of cells presenting FabP4 and the percentage of mature adipocytes with large lipid droplets were increased in TRT-2, accompanied by a robust increase in FabP4 mRNA abundance and a decrease in DLK1-positive cells. In preadipocytes, CD73 was present around the nucleus and translocated towards cell membranes during differentiation. Although the percentage of CD73-positive cells was not different among treatments, its mRNA abundance, immunocytochemical staining intensity, and translocation towards cell membranes were decreased when the medium contained no FBS (TRT-2 and TRT-4). All cells showed a diffuse distribution of CD90 and CD105 and remained positive for these markers irrespective of the treatment. However, the CD90 and CD105 mRNA abundance was decreased in TRT-2 and TRT-4; i.e., in media containing no FBS. The presence of FBS increased the absolute number of cell nuclei as assessed by DAPI fluorescence. Our results suggest that bovine subcutaneous preadipocytes display typical stem cell markers. The differentiation into mature adipocytes is promoted by BSL, whereas FBS endorses cell proliferation.
Assessment of Intra- and Inter-Rater Reliability of Three Methods for Measuring Atopic Dermatitis Severity: EASI, Objective SCORAD, and IGA
Authors: Bożek Agnieszka , Reich Adam
Published: May 2017

Background: Numerous different scoring systems have been proposed for assessing the severity of atopic dermatitis (AD). Many of these methods did not undergo proper validation and reliability testing. Objective: The aim of our study was to compare the reliability and reproducibility of the Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), and Investigator Global Assessment (IGA). Methods: On the scoring day, 10 trained dermatologists evaluated 10 adult patients with AD using the EASI, oSCORAD, and IGA. All subjects were assessed twice by each physician. Correlations between measures were analysed using the Pearson correlation coefficient. The intra-class correlation coefficient (ICC) was calculated to assess intra-rater reliability; the coefficient of variation (CV) was used to assess inter-rater variability. Results: Significant positive correlations were observed between each scale in both assessments. The ICCs for the EASI and oSCORAD were 0.71 and 0.66, respectively, indicating good reliability, while the ICC for the IGA (0.54) indicated only fair reliability. The CVs for the oSCORAD and IGA were 28.1 and 33.0, respectively, indicating moderate variability. The CV for the EASI was 66.5, indicating high variability. Conclusion: Among the 3 compared scales, the oSCORAD had the highest inter-rater reliability, whereas the EASI had the highest intra-rater reliability. None of the 3 scoring methods showed a significant advantage over the other. Thus, a reliable assessment of AD severity requires the use of at least 2 independent measurements simultaneously.
Stromal Growth Differentiation Factor 15 and Its Association with Ovarian Cancer
Authors: Lima Cid A. , Jammal Millena P. , Martins-Filho Agrimaldo , Silveira Thales Parenti , Micheli Douglas C. , Tavares-Murta Beatriz M. , Murta Eddie F.C. , Nomelini Rosekeila Simões
Published: May 2017

Background/Aims: Growth differentiation factor 15 (GDF-15) is induced by pro-inflammatory cytokines. Higher levels of GDF-15 have been associated with malignancy. The aim of the study was to evaluate both tissue and serum levels of GDF-15 in ovarian neoplasms. Methods: A cohort study evaluated 31 patients with benign ovarian tumors and 34 patients with ovarian cancer were evaluated in 2 years. The inclusion criterion was histopathological diagnosis of ovarian epithelial neoplasia. Exclusion criteria were secondary malignant ovarian neoplasia and preoperative treatment. Serum and tissue levels of GDF-15 were assessed by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Chi-square test and unpaired t test were performed. Results: Serum levels were higher in the patients with malignant neoplasms than in the patients with benign tumors, yet the difference was not statistically significant. GDF-15 immunostaining was significantly more frequent in the stroma of the malignant tumors than in the stroma of the benign tumors (p = 0.0034). Conclusion: GDF-15 staining is elevated in the stroma of ovarian cancer, demonstrating that it may be a potential diagnostic and therapeutic target.
The Rise of Expanded Hemodialysis
Authors: Ronco Claudio
Published: May 2017

The low water permeability feature of original cellulosic membranes was considered an advantage in the absence of dialysis equipment that are capable of controlling water removal. The advent of ultrafiltration control systems led to the development and use of high-flux (HF) membranes that allowed improved middle molecule removal including β-2 microglobulin. Further advances in technology allowed better control over the structure and permeability of membranes. Different polymers and improved spinning modalities led to significant advances in solute removal and hemocompatibility. Inner surface modification produced a reduction in membrane thrombogenicity and protein-membrane interaction with a less tendency to fouling and permeability decay. Further evolution in technology led to the development of a new class of membranes referred to as protein-leaking membranes or super-flux or high cutoff (HCO). These membranes are more permeable than conventional HF membranes and allow some passage of proteins, including albumin. The rationale for these membranes is the need for increased clearance of low molecular weight proteins and protein-bound solutes. However, albumin loss in protein-leaking HCO membranes represents a limitation whose effect in patients is still controversial. The last evolution in the field of membranes is the development of a new class defined as “high retention onset” (HRO) due to the peculiar high sieving value in the middle to high molecular weight range. The introduction of HRO membranes in the clinical routine has enabled the development of a new concept therapy called “expanded hemodialysis.” Its simple set up and application offer the possibility to use it even in patients with suboptimal vascular access or even with an indwelling catheter. The system does not require particular hardware or unusual nursing skill. The quality of dialysis fluid is, however, mandatory to ensure a safe conduction of the dialysis session. This new therapy is likely to modify the outcome of end-stage kidney disease patients, thanks to the enhanced removal of molecules traditionally retained by current dialysis techniques.
Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer
Authors: Sarwar Romana , Mahjabeen Ishrat , Bashir Kashif , Saeed Soma , Kayani Mahmood Akhtar
Published: May 2017

Background/Aims: In mammalian cells, XRCC3 plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to thyroid cancer. In this study, we used a haplotype-based approach to investigate whether 5 selected SNPs i.e. rs1799796, rs1799794, rs861539, rs709399 and rs861530 of XRCC3 gene are associated with thyroid cancer risk in 456 cancer patients and 400 cancer-free controls. Methods: Genotyping was performed using Allele-specific PCR followed by sequencing. Statistical analysis was performed to analyse gene and haplotype association. Results: After analysis, frequency of mutant genotype/alleles of SNPs (rs1799796, p<0.0001; rs1799794, p<0.0001; rs861539, p<0.001; rs709399, p <0.0001; rs861530, p<0.002) was found significantly higher in thyroid cancer patients compared to controls. Significant associations were found for most of the variant genotypes in SNPs of rs1799794, rs1799796, rs861539, rs861530 and rs709399 in papillary thyroid and follicular cancer patients compared to other histologic subtypes of thyroid carcinoma. Additionally, haplotype analysis revealed that haplotypes, AACGA (p= 0.0005), AGTAA (p= 0.008), GATAA (p= 0.001), GGCAA (p= 0.001) were linked with significant increase in thyroid cancer risk. However, haplotype AGCGG (p= 0.0009) was associated with a significant reduced thyroid cancer risk. Conclusion: Our results suggest that common genetic variants in the XRCC3 gene of DSBR pathway may modulate thyroid cancer risk.
The Role of Input-based and Output-based Language Teaching in Learning English Phrasal Verbs by Upper-intermediate Iranian EFL Learners
Authors: Ahmadi Farida Badri , Panahandeh Essa
Published: May 2017

The present study attempts to explore the impact of input-based and output-based pedagogical approaches on learning English phrasal verbs by upper-intermediate Iranian EFL learners. It also investigates whether there is any significant difference between Iranian male and female EFL learners regarding input-based and output-based language teaching. 73 upper-intermediate English learners participated in the study, 34 of whom were males and 39 of whom were females with an age range of 17 to 28 years old. They were divided into two intact homogeneous groups, one of which received input-based approach for teaching English phrasal verbs and the other one took advantage of output-based language teaching for the same phrasal verbs. A Test of Phrasal Verbs which is made by the researcher was used for both the pre- and post-test. Three descriptive analysis and independent-samples t-tests were used to analyze the data. Regarding the first research question, an independent-samples t-test analysis indicated that there was a significant difference between input-based and output-based instruction in teaching phrasal verbs. That is, output-based language teaching outperformed input-based language teaching and leads to better learning of the English phrasal verbs. The results of the second independent-samples t-test suggested that there was no significant difference between male and female Iranian EFL learners in output-based teaching of English phrasal verbs. The study also showed no significant difference between both genders in input-based teaching of English phrasal verbs. That is, input- and output-based instructions had no effect on genders in learning phrasal verbs.
Muslim Education in Post- independent India: Past, Present and Future
Authors: Khan Intakhab Alam
Published: May 2017

The real journey of education in general and higher education in particular in India started after 1947. Education is its journey can’t stand alone but institutional roles need to be included to assess the contribution as a whole. The institutions of higher learning are considered the most important agency of social change, social transformation, and entire development of the country. Muslim education has always been a serious issue despite availability of so many academic institutions in general and minority institutions in particular. The poor condition of the Muslims’ education can’t be attributed to the government only, but the society, home, economy, motivation, employment and similar factors. The present article is a modest attempt towards exploring and analyzing the miserable state of Muslim education and associated factors.
The Role of Service Quality toward Open University Website on The Level of Student Satisfaction
Authors: Sahusilawane Wildoms , Hiariey Lilian Sarah
Published: May 2017

The purpose of this research is to find out the impact of variable service useability, information quality, and service interaction quality to students’ satisfaction in applying open-university website. The population is non-primary education students on two district areas, that is, West Ceram and Southeast Moluccas including thirty (30) respondents. This research uses purposive sampling as research method in which it fulfils total of thirty (30) respondents. The questionnaire was tested by using reliability test and validity test. Then, it was continued with classic assumption test contained of multicollinearity test, normality test, and heteroskedasticity test. After that, there was hypothesis test and discussion. The results of research in partial showed that variable service useability and service interaction quality have given positive and significant impact to students’ level of satisfaction. While, service information quality did not give significant impact to students’ level of satisfaction. Results of research conducted jointly from three variables Usability, Information Quality and Service Interaction positive and significant impact on the level of student satisfaction results of research conducted jointly from three variables Usability, Information Quality and Service Interaction positive and significant impact on the level of student satisfaction that Fhitung = 39.246 with a significance of 0.000 0.5.
Linking Educational Institutions with Police Officer Training Programs
Authors: Wood Nancy , Sereni-Massinger Christine
Published: May 2017

Community partnerships that are formed through Community Oriented Policing help to assist law enforcement officers with academy education and post academy education. The training offered in the academy and the post academy Field Training Officer Program traditionally places little to no emphasis on critical thinking, professional self-regulation, communication skills or problem-based learning. In the last several years a new approach has been spawned. The Police Training Officer Program (PTO) is an innovative form of education that focuses on problem based learning for post academy graduates. The PTO Program emphasizes adult education, problem solving, emotional intelligence, and conflict resolution. This education is necessary to assist officers in de-escalation strategies within their communities and can lend to the reduction of civil disturbances. However, currently, relatively few agencies are offering this education to their post academy graduates and none are offering it to their academy recruits due, in part, to a lack of qualified instructors. PTO instructors must be proficient and fully trained in problem based learning techniques. Through Community Oriented Policing, law enforcement agencies can address this instructor shortage by partnering with university educational institutions to secure instructors who are competent in andragogy, critical thinking, and problem-based learning.
Increasing Skills of Student in Junior High School to Problem Solving in Geometry With Guided
Authors: Pardimin Pardimin , Widodo Sri Adi
Published: May 2017

Problem-solving skills is the ability of students to solve problems. One problem-solving model is solving the problem of Polya: (1) understand the problem, (2) create a troubleshooting plan, (3) implement plans troubleshooting, and (4) step check the answers. During this time problem-solving skills possessed by students are not satisfactory because the student in solving problems not yet using the steps systematically. So, we need a way to improve students' ability to solve problems, such as by way of providing guidance in solving a problem.
The Impact of Attending Religious Schools on the Moral Competencies of Accounting Students
Authors: Zubairu Umaru Mustapha
Published: May 2017

For over a century, scholars have argued that religious education is crucial for the developed of students' moral competencies. This study sought to empirically test this assertion by comparing the moral competencies of two sets of Muslim accounting students: those who had attended a religious secondary school and those who attended a public (secular) secondary school in Malaysia. The focus on accounting students is quite important in an era where the moral competencies of accountants has been in the public eye due to their complicity in the rash of financial scandals that have plagued the business world over the last two decades. The Muslim Accountant Moral Competency Test (MAMOC) was developed by a collaboration with Islamic accounting scholars and was used to measure the students' moral competencies. Although the results revealed that there was no difference in the moral competencies of both sets of students, they both displayed satisfactory levels of moral competency which vindicates the Malaysian government's policy of mandating Islamic education in all secondary schools, whether religious or secular.
Notice of Retraction Ethnic vs Math: The Secret inside Borobudur Temple, Indonesia
Authors: Yanuarto Wanda Nugroho
Published: May 2017

Notice of Retraction-----------------------------------------------------------------------After careful and considered review of the content of this paper by a duly constituted expert committee, this paper has been found to be in violation of UAD-IAES's Publication Principles.We hereby retract the content of this paper. Reasonable effort should be made to remove all past references to this paper.The presenting author of this paper has the option to appeal this decision by contacting edulearn@journal.uad.ac.id.-----------------------------------------------------------------------Mostly in Eastern religions, particularly in Indonesia the ancient Imperial cults of Borobudur temple as Buddhism, ritually celebrate their beliefs as a congregation where prayer and religious addresses are a communal activity. This culture is interesting to study whether building a place of worship is built on the cultural elements or there is a correlation with formula or complicated calculations about how the building is erected . The mathematical study for Borobudur’s architectural design has once related to answer the question about the metric system used by ancient Javanese to build such giant buildings with good measurement. Fractal dimension is calculated by using the cube counting method and found that the dimension is , which is laid between the two-dimensional plane and three dimensional space. The applied fractal geometry and self-similarity of the building is emerged as the building process implement the metric rules, since there is no universal metric standard known in ancient traditional Javanese culture thus the architecture is not based on final master plan. The paper also proposes how the hypothetical algorithmic architecture might be applied computationally in order to see some experimental generations of similar building. The paper ends with some conjectures for further challenge and  insights related to fractal geometry in Javanese traditional cultural heritages.
Careers and Trends of Engineering Graduates – A Case for Study
Authors: Nuthanapati Aruna Kumari , Rao D. N.
Published: May 2017

This paper provides a template for preparing papers for electronic production of the EduLearn. A well-prepared abstract enables the reader to identify the basic content of a document quickly and accurately, to determine its relevance to their interests, and thus to decide whether to read the document in its entirety. The Abstract should be informative and completely self-explanatory, provide a clear statement of the problem, the proposed approach or solution, and point out major findings and conclusions. The Abstract should be 100 to 150 words in length. The abstract should be written in the past tense. Standard nomenclature should be used and abbreviations should be avoided. No literature should be cited. The keyword list provides the opportunity to add keywords, used by the indexing and abstracting services, in addition to those already present in the title. Judicious use of keywords may increase the ease with which interested parties can locate our article.
Gaining Institutional Efficiency in the General Education Assessment for Technology Program Accreditation
Authors: Hossain ASM Delowar
Published: May 2017

This work addresses the need to merge various student learning assessment activities to gain efficiency. Specifically, it discusses a mechanism of institutional assessment efficiency through development of common instruments for general education assessment that can support more than one accreditation requirement.
Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production
Authors: Nocella Cristina , Carnevale Roberto , Bartimoccia Simona , Novo Marta , Cangemi Roberto , Pastori Daniele , Calvieri Camilla , Pignatelli Pasquale , Violi Francesco
Published: May 2017

The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; p<0.01). Ex vivo study showed that agonist-stimulated platelets were associated with enhanced PA (p<0.01), Toll-like receptor 4 (TLR4) expression (p<0.05), TxA2 (p<0.01) and 8-iso-PGF2α-III (p<0.01) production in CAP patients compared to controls. The study provides evidence that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggests LPS as a potential trigger for PA in CAP.

Supplementary Material to this article is available online at www.thrombosis-online.com
CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall response by distinct mechanisms in vitro
Authors: Vollack Nadine , Friese Julia , Bergmann Sabine , Tiede Andreas , Werwitzke Sonja
Published: May 2017

Development of neutralising antibodies (inhibitors) against factor VIII (FVIII) is a frequent and severe complication of replacement therapy in haemophilia A. Previous data from haemophilia A mouse model demonstrates that both CD32 inhibition and high doses of rhFVIII prevent the differentiation of FVIII-specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here, cellular targets responsible for the suppression of ASC formation by means of CD32 inhibition and high dose of rhFVIII were analysed. We investigated apoptosis on FVIII-specific MBCs using a pan caspases inhibitor, and screened for defects in rhFVIII presentation by analysing T cell release of Th1- and Th2-cytokines in vitro. Although high dose of rhFVIII suppressed ASC formation, cytokine response was not affected. Upon re-stimulation of splenocytes with high dose of rhFVIII, prevention of apoptosis fully restored the FVIII-specific recall response. In contrast, genetic deletion or inhibition of CD32 significantly altered Th1- and Th2-response. CD32 blockade and inhibition of apoptosis resulted in a partial rescue of FVIII-specific ASCs. Normal cytokine secretion could not be restored. In conclusion, suppression of FVIII-specific recall response by CD32 and high doses of rhFVIII is mediated by distinct mechanisms. High dose of rhFVIII induces apoptosis in FVIII-specific MBCs but does not influence FVIII-specific T cell response. CD32 blockade, however, may suppress the FVIII-specific recall response by two ways: i) increasing apoptosis of FVIII-specific MBCs and ii) disturbing FVIII-specific T cell response by modulating presentation of rhFVIII to CD4+ T cells in vitro.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Expectativa x Experiência: análise de avaliações publicadas em redes sociais sobre a qualidade dos serviços de meios de hospedagem classificados pelo SBClass
Authors: Temoteo Joelma Abrantes Guedes , Brandão Jammilly Mikaela Fagundes , Silva-Lacerda Jefferson Oliveira da
Published: May 2017

O cliente, ao ver uma placa fixada na entrada de um hotel apresentando determinado número de estrelas, sente-se seguro de que a infraestrutura e a qualidade dos serviços prestados foram auditadas e o empreendimento atende a vários parâmetros de qualidade, gerando uma expectativa compatível com a categoria observada. No entanto, nem sempre a superação dessas expectativas geradas nos hóspedes e a satisfação total de suas necessidades são atingidas. Partindo de tal perspectiva, o objetivo central desta pesquisa consiste em analisar a percepção de hóspedes sobre a qualidade dos serviços de meios de hospedagem, classificados pelo SBClass nas categorias de cinco e quatro estrelas a partir de avaliações divulgadas no TripAdvisor e no Booking.com. Para tanto, buscou-se identificar quais hotéis da região Nordeste foram classificados pelo SBClass nas categorias mencionadas, e analisar, de forma comparativa, as notas atribuídas a esses empreendimentos e os comentários divulgados nas referidas redes sociais. Para atender aos objetivos estabelecidos, realizou-se uma pesquisa descritiva de abordagem qualitativa. Dentre as principais constatações, destaca-se que não foi verificada diferença relevante entre as notas recebidas pelos sete meios de hospedagem analisados. Também se observou que as notas gerais do TripAdvisor para as empresas hoteleiras são maiores do que as notas gerais atribuídas pelos clientes do Booking.com.
Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study
Authors: Lerman Joseph B. , Joshi Aditya A. , Chaturvedi Abhishek , Aberra Tsion M. , Dey Amit K. , Rodante Justin A. , Salahuddin Taufiq , Chung Jonathan H. , Rana Anshuma , Teague Heather L. , Wu Jashin J. , Playford Martin P. , Lockshin Benjamin A. , Chen Marcus Y. , Sandfort Veit , Bluemke David A. , Mehta Nehal N.
Published: May 2017

Background:

Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25).

Methods:

Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (<30 hounsfield units), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy.

Results:

Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32,
P
=0.02) and similar HRP prevalence (
P
=0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22,
P
=0.001), NCB (1.18±0.33 versus 1.03±0.21,
P
=0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1–31.7;
P
=0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23–0.67;
P
<0.001) and NCB (β=0.53, 0.32–0.74;
P
<0.001) beyond traditional risk factors.

Conclusions:

Patients with psoriasis had greater NCB and increased HRP prevalence than healthy volunteers. In addition, patients with psoriasis had elevated NCB and equivalent HRP prevalence as older patients with hyperlipidemia. Last, modulation of target organ inflammation (eg, skin) was associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced coronary artery disease risk.
Ambulatory Pulse Wave Velocity Is a Stronger Predictor of Cardiovascular Events and All-Cause Mortality Than Office and Ambulatory Blood Pressure in Hemodialysis Patients
Authors: Sarafidis Pantelis A. , Loutradis Charalampos , Karpetas Antonios , Tzanis Georgios , Piperidou Alexia , Koutroumpas Georgios , Raptis Vasilios , Syrgkanis Christos , Liakopoulos Vasilios , Efstratiadis Georgios , London Gérard , Zoccali Carmine
Published: May 2017

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate–adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank
P
=0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank
P
<0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank
P
=0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187–2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.
Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Gamboa Christopher M. , Colantonio Lisandro D. , Brown Todd M. , Carson April P. , Safford Monika M.
Published: May 2017

Background

Statin therapy is a cornerstone of cardiovascular disease risk reduction for people with diabetes mellitus. Past reports have shown race‐sex differences in statin use in general populations, but statin patterns by race and sex in those with diabetes mellitus have not been thoroughly studied.

Methods and Results

Our sample of 4288 adults ≥45 years of age with diagnosed diabetes mellitus who had low‐density lipoprotein cholesterol (
LDL
‐C) >100 mg/dL or were taking statins recruited for the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007. Exposures included race‐sex groups (white men [
WM
], black men [
BM
], white women [
WW
], black women [
BW
]) and factors that may influence healthcare utilization. Proportions and prevalence ratios were calculated for statin use and
LDL
‐C control. Statin use for
WM
,
BM
,
WW
, and
BW
was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (
P
<0.001). After adjustment for healthcare utilization factors, statin use was lower for
BM
,
WW
, and
BW
compared with
WM
(prevalence ratios [95%
CI
]: 0.96 [0.89‐1.03], 0.86 [0.80‐0.92], and 0.87 [0.81‐0.93], respectively,
P
<0.001).
LDL
‐C control among those taking statins for
WM
,
BM
,
WW
, and
BW
was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (
P
<0.001). After adjustment,
LDL
‐C control was lower for
BM
,
WW
, and
BW
compared with
WM
(prevalence ratios [95%
CI
]: 0.85 [0.79‐0.93], 0.89 [0.82‐0.96], and 0.73 [0.67‐0.80], respectively,
P
<0.001).

Conclusions

Race‐sex disparities in statin use and
LDL
‐C control were only partly explained by factors influencing health services utilization. Healthcare provider awareness of these disparities may help to close the observed race‐sex gaps in statin use and
LDL
‐C control among people with diabetes mellitus.
Observed Cost and Variations in Short Term Cost‐Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III
Authors: Simpson Kit N. , Simpson Annie N. , Mauldin Patrick D. , Palesch Yuko Y. , Yeatts Sharon D. , Kleindorfer Dawn , Tomsick Thomas A. , Foster Lydia D. , Demchuk Andrew M. , Khatri Pooja , Hill Michael D. , Jauch Edward C. , Jovin Tudor G. , Yan Bernard , von Kummer Rüdiger , Molina Carlos A. , Goyal Mayank , Schonewille Wouter J. , Mazighi Mikael , Engelter Stefan T. , Anderson Craig , Spilker Judith , Carrozzella Janice , Ryckborst Karla J. , Janis L. Scott , Broderick Joseph P. ,   the Interventional Management of Stroke (IMS) III Investigators
Published: May 2017

Background

Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke)
III
Trial.

Methods and Results

Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke).

Conclusions

Detailed economic and resource utilization data from
IMS III
provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Registration number:
NCT
00359424.
What Is Actually Affected by the Scrambling of Objects When Localizing the Lateral Occipital Complex?
Authors: Margalit Eshed , Biederman Irving , Tjan Bosco S. , Shah Manan P.
Published: May 2017

The lateral occipital complex (LOC), the cortical region critical for shape perception, is localized with fMRI by its greater BOLD activity when viewing intact objects compared with their scrambled versions (resembling texture). Despite hundreds of studies investigating LOC, what the LOC localizer accomplishes—beyond distinguishing shape from texture—has never been resolved. By independently scattering the intact parts of objects, the axis structure defining the relations between parts was no longer defined. This led to a diminished BOLD response, despite the increase in the number of independent entities (the parts) produced by the scattering, thus indicating that LOC specifies interpart relations, in addition to specifying the shape of the parts themselves. LOC's sensitivity to relations is not confined to those between parts but is also readily apparent between objects, rendering it—and not subsequent “place” areas—as the critical region for the representation of scenes. Moreover, that these effects are witnessed with novel as well as familiar intact objects and scenes suggests that the relations are computed on the fly, rather than being retrieved from memory.
Recall it again, Sam. Practices of Repetition in the Security Council
Authors: Werner Wouter
Published: May 2017

Security Council resolutions seldom only appear only once. More often than not, they are recalled, reiterated, recognised, re-emphasised or reaffirmed in subsequent resolutions. In this article, I study some of the effects of such acts of repetition. Based on an analysis of acts of repetition in films and novels, I argue that acts of repetition are related to (a) the problem of origins, (b) the problem of authorship/authority and (c) the problem of continuity and change. Through acts of repetition, resolutions can claim that they had already begun before they were enacted, that there was something “before the beginning”. Moreover, acts of repetition help securing the continuity of the author (authority) of resolutions. Finally, acts of repetition make it possible to confirm and at the same time adapt earlier statements or rules of law.
Muslim Faith in Pakistan: A Faith-Development View on Fundamentalist to Mature Orientations
Authors: Tarar Amina Hanif , Hassan Syeda Salma , Keller Barbara
Published: May 2017

Faith development theory has evolved as a prominent theoretical perspective during the past three decades to explain different ways of relating to religious beliefs and worldviews. Recent revisions of the theory have elaborated on these characteristic ways as religious styles namely the fundamentalist, mutual, individuative-systemic, and dialogical. The present study developed an Urdu version of its principal measure, i.e., Faith Development Interview, to analyze twelve cases of Muslims of various religious affiliations within Islam in Pakistan. Four case studies representative of each faith style are presented in detail. The cases are compared to analyze Islamic faith in terms of faith development theory and to understand fundamentalism in a Muslim context. The findings support faith development theory as a comprehensive paradigm to address the varieties of faith orientations in Islam. Implications for future research with larger samples in highly religious and collectivistic cultures are discussed.