bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of zileuton on osteoporotic bone and its healing, expression of bone, and brain genes in rats
Authors: Saul D. , Ninkovic M. , Komrakova M. , Wolff L. , Simka P. , Gasimov T. , Menger B. , Hoffmann D. B. , Rohde V. , Sehmisch S.
Published: August 2017

Estrogen deficiency and aging are associated with osteoporosis, impaired bone healing, and lower cognitive performance. Close functional and physical connections occur between bone and the central nervous system. An anti-inflammatory drug, zileuton (which is an inhibitor of arachidonate 5-lipoxygenase), is known to have a positive effect on bone tissue repair and brain ischemia. We studied the effect of zileuton on osteopenic bone and its healing and on the genes considered to be crucial for the cross talks between bone and brain. Three-month-old Sprague-Dawley rats were ovariectomized or left untreated. After 8 wk, bilateral metaphyseal tibia osteotomy with plate osteosynthesis was performed in all rats. Ovariectomized rats were fed with food containing zileuton (1, 10, or 100 mg/kg body wt) for 5 wk. In tibiae, bone volume, callus and cortical volume, and gene expression of osteocalcin and alkaline phosphatase were enhanced by zileuton (10 or 100 mg); biomechanical properties and bone density were not changed. In femur, zileuton enlarged cortical volume distal and trabecular volume proximal, decreasing their density. The expression level of brain Sema3a, known to regulate bone mass positively, was downregulated after ovariectomy. In contrast, bone Sema4d, a negative regulator of bone mass, was upregulated in the tibia callus after ovariectomy, whereas zileuton treatment (10 or 100 mg) resulted in reverse effects. Here, we describe for the first time the expression of Rbbp4 mRNA and its increase in tibia after ovariectomy. Zileuton caused downregulation of Rbbp4 in the hippocampus and had an effect on bone healing, changed the expression of genes involved in cross talk between bones and brain, and may be a potent drug for further examination in estrogen deficiency-related dysfunction(s).

NEW & NOTEWORTHY Zileuton, a 5-lipoxygenase inhibitor, increased bone volume, callus and cortical volume in osteotomized tibia, and trabecular and cortical volume in femur. Although the expression of Sema3a (positively regulating bone mass) in brain was downregulated and Sema4d (negatively regulating bone mass) was upregulated in tibia callus after ovariectomy, zileuton could counteract these effects. Rbbp4 (involved in age-related memory loss) was increased in tibia callus after ovariectomy.
Social experience alters socially induced serotonergic fluctuations in the inferior colliculus
Authors: Keesom Sarah M. , Sloss Brooklyn G. , Erbowor-Becksen Zita , Hurley Laura M.
Published: August 2017

Past social experience and current social context shape the responses of animals to social signals. The serotonergic system is one potential mechanism by which both experiential and contextual factors could be conveyed to sensory systems, such as the auditory system, for multiple reasons. 1) Many features of the serotonergic system are sensitive to social experience. 2) Elevations in serotonergic activity are triggered by social partners, and variations in socially triggered serotonergic responses reflect behavioral differences among social encounters. 3) Serotonin is an auditory neuromodulator, altering how auditory neurons respond to sounds including conspecific vocalizations. In this study, we tested how social experience influences the socially triggered serotonergic response in the inferior colliculus, an auditory midbrain region with an important role in vocalization processing. We used carbon fiber voltammetry to measure serotonin during social interactions of male mice ( Mus musculus) from different social backgrounds: 4 weeks of grouped or individual housing. When paired with an unfamiliar male, both group-housed and individually housed males demonstrated elevations in serotonin; however, individually housed males exhibited socially triggered serotonergic responses with delayed time courses compared with the group-housed males. Furthermore, group-housed males displayed previously described correlations between the socially triggered serotonergic response and behaviors such as social investigation. In contrast, individually housed males did not show these serotonin-behavior relationships. These results suggest that social experience gained via social housing may shape the ability of the central serotonergic system to encode social context in sensory regions.

NEW & NOTEWORTHY We demonstrate that past social experience influences the fidelity with which the serotonergic system represents social context in an auditory region. Social experience altered the time course of socially triggered serotonergic responses and changed how the serotonergic system reflects behavioral variations among social encounters of the same context. These findings are significant to the study of communication, suggesting that centralized neuromodulatory systems potentially convey integrated information regarding past experience and current context to primary sensory regions.
Forty-Three-Year-Old Female with Dopamine Secreting Pheochromocytoma of the Adrenal Gland
Authors: Haden Tyler , Zuberek Marcin , Pokala Naveen
Published: August 2017

We report on a 43-year-old, asymptomatic female who presented with incidental finding of left adrenal mass. MRI gave concerns for possible pheochromocytoma but markers for pheochromocytoma were not elevated as expected. 24-hour urine dopamine levels (6988 μg/day) were significantly elevated. The patient successfully underwent robotic assisted radical left adrenalectomy and was diagnosed with a dopamine secreting pheochromocytoma. Pathology revealed increased malignant potential associated with the tumor. The patient underwent full metastatic workup, which was negative. At two years of follow-up there was no recurrence and normalization of lab values.
Convergence Analysis of Generalized Jacobi-Galerkin Methods for Second Kind Volterra Integral Equations with Weakly Singular Kernels
Authors: Cai Haotao
Published: August 2017

We develop a generalized Jacobi-Galerkin method for second kind Volterra integral equations with weakly singular kernels. In this method, we first introduce some known singular nonpolynomial functions in the approximation space of the conventional Jacobi-Galerkin method. Secondly, we use the Gauss-Jacobi quadrature rules to approximate the integral term in the resulting equation so as to obtain high-order accuracy for the approximation. Then, we establish that the approximate equation has a unique solution and the approximate solution arrives at an optimal convergence order. One numerical example is presented to demonstrate the effectiveness of the proposed method.
Interactive Segmentation of Pancreases in Abdominal Computed Tomography Images and Its Evaluation Based on Segmentation Accuracy and Interaction Costs
Authors: Takizawa Hotaka , Suzuki Takenobu , Kudo Hiroyuki , Okada Toshiyuki
Published: August 2017

The present paper proposed an interactive segmentation method of pancreases in abdominal computed tomography (CT) images based on the anatomical knowledge of medical doctors and the statistical information of pancreas shapes. This segmentation method consisted of two phases: training and testing. In the training phase, pancreas regions were manually extracted from sample CT images for training, and then a probabilistic atlas (PA) was constructed from the extracted regions. In the testing phase, a medical doctor selected seed voxels for a pancreas and background in a CT image for testing by use of our graphical user interface system. The homography transformation was used to fit the PA to the seeds. The graph cut technique whose data term was weighted by the transformed PA was applied to the test image. The seed selection, the atlas transformation, and the graph cut were executed iteratively. This doctor-in-the-loop segmentation method was applied to actual abdominal CT images of fifteen cases. The experimental results demonstrated that the proposed method was more accurate and effective than the conventional graph cut.
A Novel Approach of Impulsive Signal Extraction for Early Fault Detection of Rolling Element Bearing
Authors: Aijun Hu , Jianfeng Lin , Shangfei Sun , Ling Xiang
Published: August 2017

The fault signals of rolling element bearing are often characterized by the presence of periodic impulses, which are modulated high-frequency harmonic components. The features of early fault in rolling bearing are very weak, which are often masked by background noise. The impulsiveness of the vibration signal has affected the identification of characteristic frequency for the early fault detection of the bearing. In this paper, a novel approach based on morphological operators is presented for impulsive signal extraction of early fault in rolling element bearing. The combination Top-Hat (CTH) is proposed to extract the impulsive signal and enhance the impulsiveness of the bearing fault signal, and the envelope analysis is applied to reveal the fault-related signatures. The impulsive extraction performance of the proposed CTH is compared with that of finite impulse response filter (FIR) by analyzing the simulated bearing fault signals, and the result indicates that the CTH is more effective in extracting impulsive signals. The method is evaluated using real fault signals from defective bearings with early rolling element fault and early fault located on the outer race. The results show that the proposed method is able to enhance the impulsiveness of early bearing fault signals.
High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis
Authors: Zhang Miao , Huang Xuan-zhang , Song Yong-xi , Gao Peng , Sun Jing-xu , Wang Zhen-ning
Published: August 2017

Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR) with prognosis and clinicopathological characteristics of breast cancer.Methods. The PubMed and Embase databases were searched. Hazard ratio (HR) with 95% confidence interval (CI) was used to summarize disease-free survival (DFS) and overall survival (OS). Odds ratio (OR) was used to summarize tumor clinicopathological characteristics.Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2= 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2= 0.192). A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2< 0.001), between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22–1.91, and Tau2=0.014), and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73–6.59, and Tau2< 0.001).Conclusions. Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.
Sensitivity toBUB1BInhibition Defines an Alternative Classification of Glioblastoma
Authors: Lee Eunjee , Pain Margaret , Wang Huaien , Herman Jacob A. , Toledo Chad M. , DeLuca Jennifer G. , Yong Raymund L. , Paddison Patrick , Zhu Jun
Published: August 2017

Glioblastoma multiforme (GBM) remains a mainly incurable disease in desperate need of more effective treatments. In this study, we develop evidence that the mitotic spindle checkpoint molecule BUB1B may offer a predictive marker for aggressiveness and effective drug response. A subset of GBM tumor isolates requires BUB1B to suppress lethal kinetochore–microtubule attachment defects. Using gene expression data from GBM stem-like cells, astrocytes, and neural progenitor cells that are sensitive or resistant to BUB1B inhibition, we created a computational framework to predict sensitivity to BUB1B inhibition. Applying this framework to tumor expression data from patients, we stratified tumors into BUB1B-sensitive (BUB1BS) or BUB1B-resistant (BUB1BR) subtypes. Through this effort, we found that BUB1BS patients have a significantly worse prognosis regardless of tumor development subtype (i.e., classical, mesenchymal, neural, proneural). Functional genomic profiling of BUB1BR versus BUB1BS isolates revealed a differential reliance of genes enriched in the BUB1BS classifier, including those involved in mitotic cell cycle, microtubule organization, and chromosome segregation. By comparing drug sensitivity profiles, we predicted BUB1BS cells to be more sensitive to type I and II topoisomerase inhibitors, Raf inhibitors, and other drugs, and experimentally validated some of these predictions. Taken together, the results show that our BUB1BR/S classification of GBM tumors can predict clinical course and sensitivity to drug treatment. Cancer Res; 77(20); 5518–29. ©2017 AACR.
Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury
Authors: Heery Christopher R. , Palena Claudia , McMahon Sheri , Donahue Renee N. , Lepone Lauren M. , Grenga Italia , Dirmeier Ulrike , Cordes Lisa , Marté Jenn , Dahut William , Singh Harpreet , Madan Ravi A. , Fernando Romaine I. , Hamilton Duane H. , Schlom Jeffrey , Gulley James L.
Published: August 2017

Purpose: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance to therapy of human tumor cells. This study describes the characterization of a Modified Vaccinia Ankara (MVA) vector–based vaccine expressing the transgenes for brachyury and three human costimulatory molecules (B7.1, ICAM-1, and LFA-3, designated TRICOM) and a phase I study with this vaccine.

Experimental Design: Human dendritic cells (DC) were infected with MVA-brachyury-TRICOM to define their ability to activate brachyury-specific T cells. A dose-escalation phase I study (NCT02179515) was conducted in advanced cancer patients (n = 38) to define safety and to identify brachyury-specific T-cell responses.

Results: MVA-brachyury-TRICOM-infected human DCs activated CD8+ and CD4+ T cells specific against the self-antigen brachyury in vitro. No dose-limiting toxicities were observed due to vaccine in cancer patients at any of the three dose levels. One transient grade 3 adverse event (AE) possibly related to vaccine (diarrhea) resolved without intervention and did not recur with subsequent vaccine. All other AEs related to vaccine were transient and ≤grade 2. Brachyury-specific T-cell responses were observed at all dose levels and in most patients.

Conclusions: The MVA-brachyury-TRICOM vaccine directed against a transcription factor known to mediate EMT can be administered safely in patients with advanced cancer and can activate brachyury-specific T cells in vitro and in patients. Further studies of this vaccine in combination therapies are warranted and planned. Clin Cancer Res; 23(22); 6833–45. ©2017 AACR.
A Retrospective Analysis of γδ T Cell Expression in Chronic Rhinosinusitis and Its Association with Recurrence of Nasal Polyps
Authors: Lee Wenting , Chang Lihong , Huang Zizhen , Huang Jiancong , Yang Luoying , Wang Zhiyuan , Zhang Gehua
Published: August 2017

Background/Aims: To examine whether γδ T cell is expressed in the nasal mucosa of chronic rhinosinusitis (CRS) patients and its potential association with recurrence of nasal polyps. Methods: Thirty-six patients with CRS with nasal polyps (CRSwNP) and 25 patients with CRS without nasal polyps (CRSsNP) were recruited. Twenty-six patients with other nasal diseases served as controls. The CRSwNP group was divided into the eosinophilic CRSwNP and noneosinophilic CRSwNP groups. The expression of γδ T cells was detected by immunohistochemistry. The expression of each subtype of γδ T cells was detected by using qRT-PCR. All patients underwent nasal endoscopy, and postoperative follow-up lasted over 12 months. CRS patients were evaluated by preoperative VAS scores of symptoms and nasal endoscopy Lund-Kennedy scores. Results: The expression of γδ T cells in the CRSwNP groups was stronger than in the CRSsNP and the control group (p < 0.05, p < 0.05). The expression of Vγ1+γδ T cells in the eosinophilic CRSwNP group was higher than that in the CRSsNP group and the control group (p < 0.05, p < 0.05). The expression of γδ T cells was associated with high rate of recurrence, tissue eosinophil infiltration, worse symptom score of nasal obstruction, and higher Lund-Kennedy score (all p < 0.05). Conclusions: Increased expression of γδ T cells in CRSwNP may be associated with recurrence of nasal polyps.
Variants in Chemosensory Genes Are Associated with Picky Eating Behavior in Preschool-Age Children
Authors: Cole Natasha Chong , Wang Anthony A. , Donovan Sharon M. , Lee Soo-Yeun , Teran-Garcia Margarita ,   the STRONG Kids Team
Published: August 2017

Background/Aims: Picky eating is prevalent among preschoolers and is associated with risk of both underweight and overweight. Although differences in taste perception may be due to genetic variation, it is unclear whether these variations are related to picky eating behavior. The aim of this study was to investigate the association of 6 single nucleotide polymorphisms (SNPs) in 5 candidate genes related to chemosensory perception with picky eating behavior and adiposity in a cohort of preschool-aged children. Methods: Parents of 2- to 5-year-old non-Hispanic white preschoolers (n = 153) responded to survey questions on demographics, and information regarding their child's breastfeeding history and picky eating behavior. Height and weight were measured to calculate body mass index (BMI) z-scores using standard growth charts, and saliva was collected for genotyping. Generalized linear models were used to examine associations between picky eating behavior and BMI z-scores with genetic variation. Results: When controlling for child age, sex, breastfed status, and parent education level, SNPs in TAS2R38 (rs713598) and CA6 (rs2274327) were associated with picky eating behavior in children. There was no association between SNPs and BMI z-scores. Conclusion: Genes related to chemosensory perception may play a role in children's picky eating behavior.
The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo
Authors: Koymans Kirsten J. , Goldmann Oliver , Karlsson Christofer A.Q. , Sital Wiedjai , Thänert Robert , Bisschop Adinda , Vrieling Manouk , Malmström Johan , van Kessel Kok P.M. , de Haas Carla J.C. , van Strijp Jos A.G. , Medina Eva
Published: August 2017

Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic properties of SSL3 and SSL4, we compared the infection with wild-type and SSL3/4 knockout S. aureus strains in an intravenous murine infection model. Direct evaluation of the contribution of SSL3/4 to infection pathogenesis was hindered by the fact that the SSLs were not expressed in the murine system. To circumvent this limitation, an SSL3-overproducing strain (pLukM-SSL3) was generated, resulting in constitutive expression of SSL3. pLukM-SSL3 exhibited increased virulence compared to the parental strain in a murine model that was found to be TLR2 dependent. Altogether, these data indicate that SSL3 contributes to S. aureus virulence in vivo.
Review of the Diagnostic Evaluation of Normal Anion Gap Metabolic Acidosis
Authors: Berend Kenrick
Published: August 2017

Background: Normal anion gap metabolic acidosis is a common but often misdiagnosed clinical condition associated with diarrhea and renal tubular acidosis (RTA). Early identification of RTA remains challenging for inexperienced physicians, and diagnosis and treatment are often delayed. Summary: The presence of RTA should be considered in any patient with a high chloride level when the CL-/Na+ ratio is above 0.79, if the patient does not have diarrhea. In patients with significant hyperkalemia one should evaluate for RTA type 4, especially in diabetic patients, with a relatively conserved renal function. A still growing list of medications can produce RTA. Key Messages: This review highlights practical aspects concerning normal anion gap metabolic acidosis.
Use of Intravitreal Dexamethasone in a Case of Anterior Ischemic Optic Neuropathy
Authors: Nuzzi Raffaele , Monteu Francesca
Published: August 2017

Nowadays there is no unique and well-established treatment for nonarteritic anterior ischemic optic neuropathy, despite being the main acute pathology that affects the optic nerve in the elderly population and often resulting in a significant loss of visual acuity. The effectiveness of oral steroids is still under debate in the international literature, although many studies show that patients treated with high doses of systemic corticosteroids have a significantly higher chance of improved visual acuity and visual fields. The authors propose an intravitreal dexamethasone injection/implant as initial and acute therapy. Compared to systemic corticosteroids, intravitreal dexamethasone has the advantage of avoiding any systemic side effects of steroids. On the other hand, a rise in intraocular pressure might occur, manageable with local antiglaucoma drugs, especially in patients at risk, and there is a risk of induced cataract. The pharmacodynamics of the intravitreal dexamethasone slow-release implant is characterized by a first step with high release concentrations and a second following phase with decreasing concentrations. Therefore, the use of emergency dexamethasone (high concentration) intravitreal injection is justified as a treatment after the first detection of an ischemic optic anterior neuropathy.
Pancreas Cancer Precision Treatment Using Avatar Mice from a Bioinformatics Perspective
Authors: Perales-Patón Javier , Piñeiro-Yañez Elena , Tejero Héctor , López-Casas Pedro P. , Hidalgo Manuel , Gómez-López Gonzalo , Al-Shahrour Fátima
Published: August 2017

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death among solid malignancies. Unfortunately, PDAC lethality has not substantially decreased over the past 20 years. This aggressiveness is related to the genomic complexity and heterogeneity of PDAC, but also to the absence of an effective screening for the detection of early-stage tumors and a lack of efficient therapeutic options. Therefore, there is an urgent need to improve the arsenal of anti-PDAC drugs for an effective treatment of these patients. Patient-derived xenograft (PDX) mouse models represent a promising strategy to personalize PDAC treatment, offering a bench testing of candidate treatments and helping to select empirical treatments in PDAC patients with no therapeutic targets. Moreover, bioinformatics-based approaches have the potential to offer systematic insights into PDAC etiology predicting putatively actionable tumor-specific genomic alterations, identifying novel biomarkers and generating disease-associated gene expression signatures. This review focuses on recent efforts to individualize PDAC treatments using PDX models. Additionally, we discuss the current understanding of the PDAC genomic landscape and the putative druggable targets derived from mutational studies. PDAC molecular subclassifications and gene expression profiling studies are reviewed as well. Finally, latest bioinformatics methodologies based on somatic variant detection and prioritization, in silico drug response prediction, and drug repositioning to improve the treatment of advanced PDAC tumors are also covered.
Early Intervention with Infliximab Prevents Reoperation in Crohn's Disease: A Single-Center Retrospective Analysis
Authors: Ishii Manabu , Tarumi Ken-ichi , Shiotani Akiko , Kamada Tomoari , Fujita Minoru , Matsumoto Hiroshi , Murao Takahisa , Manabe Noriaki , Kusunoki Hiroaki , Hata Jiro , Haruma Ken
Published: August 2017

Background/Aims: We aimed to evaluate the prognostic factors that can aid in the prevention of first and second surgeries in patients with Crohn's disease (CD). Methods: The clinical records of 115 patients with CD whose disease onset was between January 1987 and July 2012 were retrospectively investigated. The cumulative rate of bowel resection for CD-related intestinal manifestations following onset until the first surgery and the cumulative rate of reoperation following the first to second surgeries were estimated using the Kaplan-Meier method, and the relationship to each factor was statistically analyzed using the log-rank test. The background factors that influenced the cumulative rate of the first surgery and reoperation were evaluated using univariate and multivariate analyses. Results: The cumulative bowel resection rate was significantly higher in patients with ileocolitis-type CD (p = 0.0018) and in those with CD with smoking habits (p = 0.0315). And the cumulative reoperation rate was significantly higher in patients with ileocolitis-type CD (p = 0.0161) and those without early intervention with infliximab (p = 0.0161). Conclusions: Ileocolitis-type CD and smoking habit might be initiating factors for bowel resection due to CD-related intestinal manifestations. Early intervention with infliximab likely prevents reoperation for CD recurrence.
Association between Testosterone and Mortality Risk among U.S. Males Receiving Dialysis
Authors: Yu Jerry , Ravel Vanessa A. , You Amy S. , Streja Elani , Rivara Matthew B. , Potukuchi Praveen K. , Brunelli Steven M. , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar , Rhee Connie M.
Published: August 2017

Background: Among the general population, low circulating testosterone levels are associated with higher risk of cardiovascular disease and death. While testosterone deficiency is common in dialysis patients, studies of testosterone and mortality in this population are ambiguous and overlapping. We hypothesized that lower testosterone levels are associated with higher mortality in male dialysis patients. Methods: We examined a nationally representative cohort of male dialysis patients from a large US dialysis organization who underwent one or more total testosterone measurements from 1/2007 to 12/2011. The association between total testosterone categorized as quartiles and all-cause mortality was studied using Cox models adjusted for expanded case-mix and laboratory covariates. We also examined total testosterone as a continuous predictor of all-cause mortality using restricted cubic splines. Results: Among 624 male dialysis patients, 51% of patients demonstrated testosterone deficiency (total testosterone <300 ng/dL); median (IQR) total testosterone levels were 297 (190-424) ng/mL. In expanded case-mix + laboratory adjusted Cox analyses, we observed a graded association between lower testosterone levels and higher mortality risk (ref: quartile 3): adjusted hazard ratios (95% CI) 2.32 (1.33-4.06), 1.80 (0.99-3.28), and 0.68 (0.32-1.42) for Quartiles 1, 2, and 4, respectively. In adjusted spline analyses, the lower testosterone-higher mortality risk association declined with higher testosterone levels until the value reached a threshold of 400 ng/dL above which risk plateaued. Conclusion: Lower testosterone levels were independently associated with higher mortality risk in male dialysis patients. Further studies are needed to determine underlying mechanisms, and whether testosterone replacement ameliorates death risk in this population.
Códigos, símbolos e sinais: o caso dos Ex-votos Mexicanos
Authors: Oliveira José Cláudio Alves de
Published: August 2017

O presente artigo, mais uma produção do Projeto Ex-votos do México, se aporta na semiótica, iconografia e iconologia para analisar alguns casos representados pelos ex-votos mexicanos, como fonte de estudos da comunicação social, representativos da identidade cultural, e enaltecidos como media da cultura popular, que a partir da simplicidade da escrita, formas e traços artísticos e abstratos, elucidam questões individuais e coletivas.
Risk factors for Toxoplasma gondii infection in sheep in the northeastern region of Brazil
Authors: Rizzo Huber , Gaeta Natália Carrillo , HORA João Henrique Costa , Carvalho Jeferson Da Silva , Pinheiro Júnior José Wilton , Gennari Solange Maria , Pena Hilda Fátima de Jesus , Villalobos Eliana Monteforte Cassaro , Gregory Lilian
Published: August 2017

Toxoplasma gondii e um parasita cuja infecção leva a desordens reprodutivas como aborto, mumificação fetal, nascimento de cordeiros fracos e natimortos, provocando perdas econômicas na produção ovina. A região nordeste do Brasil possui aproximadamente 171 milhões de pequenos ruminantes, dos quais 5,4% são ovinos. Este estudo tem como objetivo determinar a ocorrência de T. gondii nos rebanhos ovinos de 60 propriedades de 19 municípios de três mesorregiões (leste, semiárido e sertão) do estado de Sergipe, Brasil, e os fatores de risco associados a essa infecção. Amostras de soro foram coletadas entre 2011 e 2012, em 60 propriedades localizadas em 19 municípios das três mesorregiões: 680 na região leste, 280 no semiárido e 240 no sertão, totalizando 1.200 amostras (990 fêmeas e 210 machos). Anticorpos anti-T.gondii foram detectados por reação de imunofluorescência indireta (RIF ≥ 64). A maior ocorrência foi detectada na região leste (45,3%, p = 0.001). Em propriedades com produção de subsistência, o risco de animais infectados por T. gondii e aproximadamente duas vezes maior que nas de cria/recria/engorda (OR = 3.03/ IC: 1.97-4.68). A ausência de cuidados sanitários, como ausência de esterqueira (p = 0.000/ OR: 1.60; CI: 1.26-2.03); quarentena (p = 0.000/ OR: 1.87; CI: 1.45-2.41) e desinfecção (p = 0.003/ OR: 1.46; CI: 1.13-1.88) foram significantes. Em relação a alimentação, o risco de infecção aumenta 1.74 e 1.37 em locais que utilizam cocho ou com presença de gatos, respectivamente. Este estudo permite concluir que o T. gondii e encontrado em propriedades das mesorregiões do estado de Sergipe e fatores ambientais e de manejo estão influenciando nas infecções em ovinos.
Comparative leukocyte morphometric analysis between endemic Anurans from Brazil and the invasive species Lithobates catesbeianus
Authors: Silva Stephanie Moira Rodrigues e , Ewbank Ana Carolina , Strefezzi Ricardo De Francisco , Alvarado Gilbert , Sacristan Carlos , Paula Cátia Dejuste de , Catão-Dias José Luiz
Published: August 2017

Anfíbios são indicadores ambientais potencialmente confiáveis e eficientes. Estudos referentes a morfologia de leucócitos de anuros são limitados, com poucos estudos morfometricos disponíveis em literatura. O presente estudo empregou técnicas morfometricas para caracterizar leucócitos de anuros Neotropicais brasileiros selecionados e compara-los com a espécie exótica rã-touro (Lithobates catesbeianus), família Ranidae. Esfregaços sanguíneos de 28 espécimes pertencentes a seis gêneros diferentes (Hyla, Phyllomedusa, Hypsiboas, Scinax, Physalaemus e Proceratophrys) foram comparados com amostras de esfregacos de L. catesbeianus. A média do diâmetro dos leucócitos foi calculada por um software de análise de imagens. One-way e teste de Bonferroni foram utilizados para avaliação estatística. Linfócitos, neutrófilos, eosinófilos e basófilos mostraram-se significativamente menores que os valores de referência reportados em outros gêneros de anfíbios, incluindo Lithobathes; por outro lado, a média do diâmetro dos monócitos não demonstrou variação significativa entre os gêneros. Esse e o primeiro estudo de avaliação morfometrica de leucócitos em espécies de anuros brasileiros. Nossos resultados sugerem que a separação geográfica possivelmente influencia a morfometria leucocitaria.
Polarização e construção da força discursiva em manifestos políticos: o caso das presidenciais portuguesas de 2016
Authors: Pinto Maria Alexandra Araújo Guedes , Pinho Ana Catarina Fonseca Almeida e , Teixeira Joana Filipa Pinto
Published: August 2017

O presente estudo analisa o manifesto político apresentado publicamente por um dos dez candidatos às eleições presidenciais portuguesas de janeiro de 2016. O objetivo do estudo é, através do quadro de análise proposto por Adam (2001) para a descrição dos gê- neros textuais em oito componentes (semântica; composicional; enunciativa; pragmática; estilístico-fraseológica; metatextual; peritextual e material), proceder a uma análise completa e integrada do texto, que torne visíveis os princípios centrais da sua organização argumentativa enunciativa e pragmática e, logo, os princípios da sua força discursiva. Ao mesmo tempo, a análise contribuirá para a descrição deste gênero de texto, pertencente ao tipo de discurso político, situando o texto numa zona prototípica do gênero.
Um olhar sobre vozes e poder no telejornal: o funcionamento do discurso reportado no Jornal Nacional da Rede Globo
Authors: Cunha Dóris de Arruda Carneiro da
Published: August 2017

Este artigo se propõe a apresentar algumas reflexões sobre vozes e poder no telejornalismo, com base num estudo de caso, uma notícia do Jornal Nacional do Grupo Globo. A questão central é sobre o poder do editor e dos jornalistas na construção da notícia, constituída majoritariamente por meio de discursos reportados. No telejornal analisado, as formas de inserção do heterodiscurso são pouco diversificadas e aparentemente neutras: o discurso citante do editor e apresentador chama a jornalista que introduz outras vozes – fragmentos de entrevista, de declarações oficiais, de testemunhos, na forma de citação direta ou indireta. A estratégia é não usar formas linguísticas que mostrem explicitamente seus pontos de vista. No entanto, as vozes selecionadas servem para ilustrar e acentuar os pontos de vista velados da empresa e dos seus profissionais, funcionando como argumento de autoridade. Dessa forma, a TV Globo exerce seu poder manipulando o grande público, pouco atento a essa estratégia, que faz crer que a notícia do Jornal Nacional é neutra e detentora de verdade.
Debate eleitoral português: presidencialização e estratégias de atenuação linguística em situação de confronto político
Authors: Marques Maria Aldina
Published: August 2017

Num contexto de progressiva presidencialização das campanhas eleitorais para eleições legislativas, pretende-se estudar a atenuação como uma característica do debate político eleitoral português, um gênero do discurso político marcado pela interseção com o discurso mediático televisivo. O debate político eleitoral é um gênero agónico, de confronto direto entre participantes-adversários, que pretendem obter a adesão dos eleitores pelas propostas que apresentam e também, senão sobretudo, pela descredibilização do adversário político. Este confronto não é, contudo, absoluto, pois os interlocutores têm que garantir dimensões básicas da comunicação política, assegurando, pela construção, negociação e cogestão da relação interpessoal, a preservação de uma imagem individual positiva na relação com o eleitorado. Estabelecemos como hipótese que, neste processo, a atenuação linguística constitui uma estratégia nuclear, realizada em cada momento do debate segundo procedimentos linguístico-discursivos diversos. O debate eleitoral analisado realizou-se em maio de 2011, na RTP, entre Pedro Passos Coelho, líder do Partido Social Democrata, e futuro primeiro-ministro, e José Sócrates, do Partido Socialista, primeiro-ministro em funções, na altura.
Practice Patterns and In-Hospital Outcomes Associated With Bivalirudin Use Among Patients With Non–ST-Segment–Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention in the United States
Authors: Secemsky Eric A. , Kirtane Ajay , Bangalore Sripal , Jovin Ion S. , Patel Dhavalkumar , Ferro Enrico G. , Wimmer Neil J. , Roe Matthew , Dai David , Mauri Laura , Yeh Robert W.
Published: August 2017

Background—

Practice patterns in anticoagulant strategies used during percutaneous coronary intervention (PCI) in the United States for patients with non–ST-segment–elevation myocardial infarction and the comparative outcomes between bivalirudin and unfractionated heparin (UFH) have not been well described.

Methods and Results—

Trends in anticoagulant use were examined among 553 562 PCIs performed by 9254 operators at 1538 hospitals for non–ST-segment–elevation myocardial infarction from 2009 to 2014 within the CathPCI Registry. To compare bivalirudin with UFH, propensity score matching and instrumental variable (IV) methods with operator preference for bivalirudin as the instrument were used. To determine whether differences in outcomes were because of differences in glycoprotein IIb/IIIa inhibitor (GPI) use, a test of mediation was performed using the IV. Outcomes were in-hospital bleeding and mortality. Bivalirudin use increased from 2009 to 2013 but declined during 2014. GPI use was 50.5% during UFH PCIs and 12.0% during bivalirudin PCIs. Before GPI adjustment, bleeding reductions with bivalirudin ranged from 2.04% (IV: 95% confidence interval [CI]: 1.81%, 2.27%) to 2.29% (propensity score: 95% CI: 2.14%, 2.44%) and mortality reductions ranged from 0.16% (IV: 95% CI: 0.03%, 0.28%) to 0.25% (propensity score: 95% CI: 0.17%, 0.33%). After GPI adjustment in the IV, more than half the bleeding reduction with bivalirudin was because of the lower use of GPIs (risk difference, −0.84%; 95% CI: −1.11%, −0.57%), and no survival benefit was apparent (risk difference, −0.10%; 95% CI: −0.24%, 0.05%). Bleeding reductions with bivalirudin were largest for transfemoral PCI (GPI-adjusted risk difference, −1.11%; 95% CI: −1.43%, −0.80%) and negligible for transradial PCI (GPI-adjusted risk difference, 0.09%; 95% CI: −0.32%, 0.50%).

Conclusions—

In the largest comparative analysis of bivalirudin versus UFH for non–ST-segment–elevation myocardial infarction to date, bivalirudin was associated with lower in-hospital bleeding and mortality given current practices with respect to GPI use and access site. Bleeding differences were, in part, explained by the greater use of GPIs with UFH. Reductions in bleeding were largest among those undergoing transfemoral PCI, whereas no bleeding benefit was observed for those treated with transradial PCI.
Reducing the Global Burden of Cardiovascular Disease, Part 2
Authors: Leong Darryl P. , Joseph Philip G. , McKee Martin , Anand Sonia S. , Teo Koon K. , Schwalm Jon-David , Yusuf Salim
Published: August 2017

In this second part of a 2-part series on the global burden of cardiovascular disease, we review the proven, effective approaches to the prevention and treatment of cardiovascular disease. We specifically review the management of acute cardiovascular diseases, including acute coronary syndromes and stroke; the care of cardiovascular disease in the ambulatory setting, including medical strategies for vascular disease, atrial fibrillation, and heart failure; surgical strategies for arterial revascularization, rheumatic and other valvular heart disease, and symptomatic bradyarrhythmia; and approaches to the prevention of cardiovascular disease, including lifestyle factors, blood pressure control, cholesterol-lowering, antithrombotic therapy, and fixed-dose combination therapy. We also discuss cardiovascular disease prevention in diabetes mellitus; digital health interventions; the importance of socioeconomic status and universal health coverage. We review building capacity for conduction cardiovascular intervention through strengthening healthcare systems, priority setting, and the role of cost effectiveness.
Role of Total, Red, Processed, and White Meat Consumption in Stroke Incidence and Mortality: A Systematic Review and Meta‐Analysis of Prospective Cohort Studies
Authors: Kim Kyuwoong , Hyeon Junghyeon , Lee Sang Ah , Kwon Sung Ok , Lee Hyejin , Keum NaNa , Lee Jong‐Koo , Park Sang Min
Published: August 2017

Background

Previous meta‐analyses on meat intake and risk of stroke did not report the effect of white meat (poultry meat, excluding fish) and did not examine stroke incidence and mortality separately. We aimed to investigate the relationship of total (red and processed meat), red (unprocessed or fresh red meat), and processed (processed red meat) consumption along with white meat on risk of stroke incidence and mortality.

Methods and Results

Articles were identified from databases and reference lists of relevant studies up to October 28, 2016. We selected prospective cohort studies on meat consumption specified by types of meat and stroke incidence and mortality reporting relative risks and 95% confidence intervals. The pooled relative risk was estimated using the random‐effects model. Based on the inclusion criteria, 10 articles containing 15 studies (5 articles with 7 studies including 9522 cases of stroke incidence and 254 742 participants and 5 articles with 8 studies containing 12 999 cases of stroke mortality and 487 150 participants) were selected for quantitative synthesis. The pooled relative risks (95% confidence intervals) for total, red, processed and white meat consumption and total stroke incidence were 1.18 (1.09–1.28), 1.11 (1.03–1.20), 1.17 (1.08–1.25), and 0.87 (0.78–0.97), respectively. Total meat consumption (0.97 [0.85–1.11]) and red meat consumption 0.87 (0.64–1.18) were not significantly associated with stroke‐related death.

Conclusions

The relationship between meat intake and risk of stroke may differ by type of meat. Recommendations for replacing proportions of red and processed meats to white meat for the prevention of stroke may be considered in clinical practice.
Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index
Authors: AlGhatrif Majd , Zane Ariel , Oberdier Matt , Canepa Marco , Studenski Stephanie , Simonsick Eleanor , Spencer Richard G. , Fishbein Kenneth , Reiter David , Lakatta Edward G. , McDermott Mary M. , Ferrucci Luigi
Published: August 2017

Background

Lower muscle mitochondrial energy production may contribute to impaired walking endurance in patients with peripheral arterial disease. A borderline ankle‐brachial index (ABI) of 0.91 to 1.10 is associated with poorer walking endurance compared with higher
ABI
. We hypothesized that in the absence of peripheral arterial disease, lower
ABI
is associated with lower mitochondrial energy production.

Methods and Results

We examined 363 men and women participating in the Baltimore Longitudinal Study of Aging with an
ABI
between 0.90 and 1.40. Muscle mitochondrial energy production was assessed by post‐exercise phosphocreatine recovery rate constant (

k
PC

r) measured by phosphorus magnetic resonance spectroscopy of the left thigh. A lower post‐exercise phosphocreatine recovery rate constant reflects decreased mitochondria energy production.The mean age of the participants was 71±12 years. A total of 18.4% had diabetes mellitus and 4% were current and 40% were former smokers. Compared with participants with an
ABI
of 1.11 to 1.40, those with an
ABI
of 0.90 to 1.10 had significantly lower post‐exercise phosphocreatine recovery rate constant (19.3 versus 20.8 ms
−1
,
P
=0.015). This difference remained significant after adjusting for age, sex, race, smoking status, diabetes mellitus, body mass index, and cholesterol levels (
P
=0.028). Similarly, post‐exercise phosphocreatine recovery rate constant was linearly associated with
ABI
as a continuous variable, both in the
ABI
ranges of 0.90 to 1.40 (standardized coefficient=0.15,
P
=0.003) and 1.1 to 1.4 (standardized coefficient=0.12,
P
=0.0405).

Conclusions

An
ABI
of 0.90 to 1.10 is associated with lower mitochondrial energy production compared with an
ABI
of 1.11 to 1.40. These data demonstrate adverse associations of lower
ABI
values with impaired mitochondrial activity even within the range of a clinically accepted definition of a normal
ABI
. Further study is needed to determine whether interventions in persons with
ABIs
of 0.90 to 1.10 can prevent subsequent functional decline.
Neuropathology of White Matter Lesions, Blood–Brain Barrier Dysfunction, and Dementia
Authors: Hainsworth Atticus H. , Minett Thais , Andoh Joycelyn , Forster Gillian , Bhide Ishaan , Barrick Thomas R. , Elderfield Kay , Jeevahan Jamuna , Markus Hugh S. , Bridges Leslie R.
Published: August 2017

Background and Purpose—

We tested whether blood–brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study).

Methods—

Using digital pathology, we quantified blood–brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T
2
magnetic resonance imaging (MRI)–detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1).

Results—

Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79–1.03;
P
=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77–1.12;
P
=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58–0.94;
P
=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25–4.08;
P
=0.007).

Conclusions—

Our data suggest that some degree of blood–brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.