bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Receiving Predictive Genetic Information about Lynch Syndrome on Individual Colonoscopy and Smoking Behaviors
Authors: Kim Joanne Soo-Min , Coyte Peter C. , Cotterchio Michelle , Keogh Louise A. , Flander Louisa B. , Gaff Clara , Laporte Audrey
Published: August 2016

Background: This study investigated whether receiving the results of predictive genetic testing for Lynch syndrome, indicating the presence or absence of an inherited predisposition to various cancers, including colorectal cancer, was associated with change in individual colonoscopy and smoking behaviors, which could prevent colorectal cancer.

Methods: The study population included individuals with no previous diagnosis of colorectal cancer, whose families had already identified deleterious mutations in the mismatch repair or EPCAM genes. Hypotheses were generated from a simple health economics model and tested against individual-level panel data from the Australasian Colorectal Cancer Family Registry.

Results: The empirical analysis revealed evidence consistent with some of the hypotheses, with a higher likelihood of undergoing colonoscopy in those who discovered their genetic predisposition to colorectal cancer and a lower likelihood of quitting smoking in those who discovered their lack thereof.

Conclusions: Predictive genetic information about Lynch syndrome was associated with change in individual colonoscopy and smoking behaviors but not necessarily in ways to improve population health.

Impact: The study findings suggest that the impact of personalized medicine on disease prevention is intricate, warranting further analyses to determine the net benefits and costs. Cancer Epidemiol Biomarkers Prev; 25(11); 1524–33. ©2016 AACR.
Recurrent TRIO Fusion in Nontranslocation–Related Sarcomas
Authors: Delespaul Lucile , Lesluyes Tom , Pérot Gaëlle , Brulard Céline , Lartigue Lydia , Baud Jessica , Lagarde Pauline , Le Guellec Sophie , Neuville Agnès , Terrier Philippe , Vince-Ranchère Dominique , Schmidt Susanne , Debant Anne , Coindre Jean-Michel , Chibon Frédéric
Published: August 2016

Purpose: Despite various differences, nontranslocation-related sarcomas (e.g., comprising undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxofibrosarcoma) are unified by their complex genetics. Extensive analysis of the tumor genome using molecular cytogenetic approaches showed many chromosomal gains, losses, and translocations per cell. Genomic quantitative alterations and expression variations have been extensively studied by adapted high-throughput approaches, yet translocations still remained unscreened. We therefore analyzed 117 nontranslocation-related sarcomas by RNA sequencing to identify fusion genes.

Experimental design: We performed RNA sequencing and applied a bioinformatics pipeline dedicated to the detection of fusion transcripts. RT-PCR and Sanger sequencing were then applied to validate predictions and to search for recurrence and specificity.

Results: Among the 6,772 predicted fusion genes, 420 were in-frame. One recurrent rearrangement, consistently involving TRIO with various partners, was identified in 5.1% of cases. TRIO translocations are either intrachromosomal with TERT or interchromosomal with LINC01504 or ZNF558. Our results suggest that all translocations led to a truncated TRIO protein either directly or indirectly by alternative splicing. TRIO rearrangement is associated with a modified transcriptomic program to immunity/inflammation, proliferation and migration, and an increase in proliferation.

Conclusions: TRIO fusions have been identified in four different sarcoma histotypes, likely meaning that they are not related to a primary oncogenic event but rather to a secondary one implicated in tumor progression. Moreover, they appear to be specific to nontranslocation-related sarcomas, as no such rearrangement was identified in sarcomas with simple genetics. More cases could lead to a significant association of these fusions to a specific clinical behavior. Clin Cancer Res; 23(3); 857–67. ©2016 AACR.
Development of a RSK Inhibitor as a Novel Therapy for Triple-Negative Breast Cancer
Authors: Ludwik Katarzyna A. , Campbell J. Preston , Li Mingzong , Li Yu , Sandusky Zachary M. , Pasic Lejla , Sowder Miranda E. , Brenin David R. , Pietenpol Jennifer A. , O'Doherty George A. , Lannigan Deborah A.
Published: August 2016

Metastatic breast cancer is an incurable disease and identification of novel therapeutic opportunities is vital. Triple-negative breast cancer (TNBC) frequently metastasizes and high levels of activated p90RSK (RSK), a downstream MEK-ERK1/2 effector, are found in TNBC. We demonstrate, using direct pharmacologic and genetic inhibition of RSK1/2, that these kinases contribute to the TNBC metastatic process in vivo. Kinase profiling showed that RSK1 and RSK2 are the predominant kinases targeted by the new inhibitor, which is based on the natural product SL0101. Further evidence for selectivity was provided by the observations that silencing RSK1 and RSK2 eliminated the ability of the analogue to further inhibit survival or proliferation of a TNBC cell line. In vivo, the new derivative was as effective as the FDA-approved MEK inhibitor trametinib in reducing the establishment of metastatic foci. Importantly, inhibition of RSK1/2 did not result in activation of AKT, which is known to limit the efficacy of MEK inhibitors in the clinic. Our results demonstrate that RSK is a major contributor to the TNBC metastatic program and provide preclinical proof-of-concept for the efficacy of the novel SL0101 analogue in vivo. Mol Cancer Ther; 15(11); 2598–608. ©2016 AACR.
A New Chromatin–Cytoskeleton Link in Cancer
Authors: Giaccia Amato J.
Published: August 2016

The set domain containing 2 (SETD2) histone methyltransferase, located at 3p2, specifically trimethylates lysine 36 of histone H3 (H3K36me3). H3K36me3 is an active mark involved in transcriptional elongation and RNA processing and a key regulator of DNA repair. In fact, SETD2 is the only methyltransferase that “writes” the H3K36me3 mark. Recent results from Park and colleagues have found a new role for SETD2 in the methylation of K40 of α-tubulin. Loss of SETD2 abolishes methylation of K40 of α-tubulin and results in a dysfunctional mitotic spindle and abnormalities in cytokinesis. Thus, SETD2 links chromatin and cytoskeleton homeostasis through its methyltransferase activity. These studies have important implications on the role of SETD2 mutations in promoting genomic instability and tumor progression. Mol Cancer Res; 14(12); 1173–5. ©2016 AACR.
C-Terminal to Intact Fibroblast Growth Factor 23 Ratio in Relation to Estimated Glomerular Filtration Rate in Elderly Population
Authors: Bożentowicz-Wikarek Maria , Owczarek Aleksander , Kocełak Piotr , Olszanecka-Glinianowicz Magdalena , Więcek Andrzej , Chudek Jerzy
Published: August 2016

Background/Aims: An analytical equivalence between intact fibroblasts growth factor(iFGF23) and C-terminal(cFGF23) assays is logically expected, however, numerous studies demonstrate lack of a strong association between them. Previously, we have demonstrated the increase in cFGF23 slightly precedes the increase of iFGF23 with the impairment of kidney excretory function; without actually analyzing the ratio between both assays, which are postulated to be affected by declining kidney function. Therefore, the aim of this study was to analyze the ratio between C and iFGF23 in relation to the estimated glomerular filtration rate (eGFR) in an elderly population. Methods: We analysed the variability of c/iFGF23 ratio in the population of 3264 elderly PolSenior study participants (≥ 65years) in the relation to eGFR calculated according full Modification of Diet in Renal Disease, serum levels of C-reactive protein (hs-CRP), and iron. Results: The log10(c/i FGF23 ratio) increased in the subsequent CKD stages. Serum iron and CRP levels reduced the log10 and increased it with age in multivariate regression analysis. Conclusions: Our results suggest impairment in the cleavage of the C-terminal FGF23 fragments with the deterioration of kidney excretory function and age in the elderly population. Inflammation and low serum iron level seems to diminish degradation capacity of FGF23 fragments.
Haemodynamic Transition after Birth: A New Tool for Non-Invasive Cardiac Output Monitoring
Authors: Freidl Thomas , Baik Nariae , Pichler Gerhard , Schwaberger Bernhard , Zingerle Barbara , Avian Alexander , Urlesberger Berndt
Published: August 2016

Background: Substantial haemodynamic changes occur during the first minutes after birth. Currently, only heart rate (HR) and arterial oxygen saturation are routinely used to monitor haemodynamic transition after birth. Objectives: The aim of the present study was to continuously assess haemodynamic changes during transition in term infants for the first time by using electrical velocimetry (EV), a new method of non-invasive cardiac output monitoring (NICOM), based on impedance cardiography technology. Methods: In this prospective observational study, term neonates delivered by elective caesarean section underwent NICOM measurements within the first 15 min after birth. The beat-to-beat measurement over a 10-second period was used to calculate cardiac output (CO) for each minute after birth. The data of CO were only accepted when the signal quality index (SQI) remained >80% during the measurement period of 10 s. Results: 100 term neonates underwent 1,500 NICOM measurements. 1,143 (76.2%) measurements were excluded because of a SQI <80%. HR and CO showed a trend to increase within the first minutes, and decreased significantly from minute 3 (HR) and 4 (CO), until minute 12 and 10, respectively. Stroke volume remained stable during the observation period. Conclusion: The present study was the first using EV for NICOM during the transition period in a larger cohort of newborn infants. Results of NICOM were similar to available echocardiography data. The possibility of NICOM offers continuous CO measurement. The present study supports the idea that CO is closely related to HR in newborn infants.
Exacerbation of Darier Disease under Interferon-α-2a Therapy with Clinical Signs of Lichen Nitidus
Authors: Karagiannidis Ioannis , Brunner Martina , Zouboulis Christos C.
Published: August 2016

Darier disease/dyskeratosis follicularis is a genodermatosis characterized by brown, oily keratotic papules and plaques in the seborrheic areas of the face and chest. Responsible for the disease are mutations in the ATP2A2 gene, encoding SERCA2, a calcium pump of the sarco-/endoplasmic reticulum. Mechanical trauma, heat, humidity, ultraviolet B radiation, oral corticosteroids and lithium are known trigger factors of the disorder. We report on a 48-year-old German woman with a flare-up of Darier disease under interferon-α-2a (IFNα-2a) therapy with clinical signs of lichen nitidus. Due to the fulminant course of the eruption, we suspected IFNα as a possible trigger. To our knowledge there are no reports regarding exacerbation of Darier disease during IFNα therapy. Possible pathogenetic mechanisms are being discussed.
Akupunkt-Anwendungen bei Asthma im Erwachsenenalter: Eine systematische Übersicht und Meta-Analyse randomisierter kontrollierter Studien
Authors: Su Li , Meng Ling , Chen Ran , Wu Weihua , Peng Bo , Man Lixin
Published: August 2016

Hintergrund: In dieser Studie wird die bestehende Evidenzlage zur Wirkung von Akupunkt-Anwendungen bei Asthma im Erwachsenenalter evaluiert. Methodik: Sechs elektronische Datenbanken wurden bis Mai 2014 auf relevante Studien hin durchsucht. In die Studie eingeschlossen wurden randomisierte, kontrollierte Studien zur Wirkung von Akupunkt-Anwendungen bei erwachsenen Asthmapatienten. Die methodische Qualität der ausgewählten Studien wurde mithilfe des Cochrane Collaboration Tools überprüft. Die standardisierte Mittelwertdifferenz (SMD) sowie die 95%-Konfidenzintervalle (KIs) eines Random-Effect-Modells wurden ermittelt. Die Heterogenität wurde durch I2-Statistiken errechnet. Ergebnisse: Insgesamt wurden acht Studien in unsere Analyse eingeschlossen. Die kumulierten Ergebnisse ergaben, dass die Akupunkt-Anwendungen die Einsekundenkapazität (FEV1) (SMD 0,32; 95%-KI 0,04-0,60; p = 0,03) sowie den FEV1/forcierte Vitalkapazität-Quotienten (SMD 0,89; 95%-KI 0,70-1,09; p < 0,00001), den Interleukin- (SMD -0,26; 95%-KI -0,50 bis -0,01; p = 0.04) und den Immunglobulin-E-Spiegel bei Asthmapatienten verbesserten. Dies traf jedoch nicht auf das eosinophile kationische Protein zu (SMD -0,58; 95%-KI -1,42 bis 0,26; p = 0,18). Die Evidenz für nachhaltige Effekte von Akupunkt-Anwendungen in der Therapie von Asthmapatienten ist nicht hinreichend. Schlussfolgerungen: Akupunkt-Anwendungen können eine sinnvolle komplementäre bzw. alternative Therapieoption bei der Behandlung von Asthma sein, vor allem zur Unterstützung der Lungenfunktion und zur Reduktion der Interleukin- und Immunglobulin-E-Level. Jedoch sind mehr Studien mit längeren Follow-up-Zeiten vonnöten, um die derzeitigen Erkenntnisse zu verifizieren.
Asthma bronchiale und belastungsinduzierte Bronchokonstriktion
Authors: Jayasinghe Harshani , Kopsaftis Zoe , Carson Kristin
Published: August 2016

Regelmäßige Bewegung wirkt sich in vielfältiger Weise gesundheitsfördernd aus, insbesondere ist ein positiver Beitrag zum Management chronischer Krankheiten wie beispielsweise Asthma umfassend dokumentiert. In manchen Fällen kann körperliche Belastung aber auch die Verschlimmerung einer Asthmaerkrankung und entsprechende akute Anfälle von Atemnot, Husten, Engegefühl in der Brust und pfeifenden Atem (Giemen) auslösen. Dieser physiologische Prozess wird als belastungsinduzierte Bronchokonstriktion (exercise-induced bronchoconstriction, EIB) bezeichnet und ist als Abnahme der Einsekundenkapazität nach körperlicher Belastung um 10-15% gegenüber dem Ausgangswert definiert. Während EIB unter Asthmatikern sehr weit verbreitet ist und sich mit einer ähnlichen respiratorischen Symptomatik manifestiert, sind Asthma und EIB nicht zwingend miteinander vergesellschaftet. Das Ziel der vorliegenden Übersichtsarbeit ist es, einen umfassenden Überblick über beide Krankheitsbilder zu geben, um die Kenntnisse über ihre Gemeinsamkeiten und Unterschiede auszubauen und ihre Unterscheidung als zwei separate Entitäten zu schärfen. Die Pathophysiologie und die Mechanismen, die der Asthmaerkrankung zugrunde liegen, sind umfassend beschrieben; derzeit konzentriert sich die Forschung darauf, Phänotypen für zielgerichtete Managementstrategien zu definieren. Die zugrunde liegenden Mechanismen der EIB hingegen sind noch weitgehend ungeklärt. Für beide gibt es ähnliche etablierte Diagnosepfade sowie ähnliche pharmakologische und nichtpharmakologische Behandlungs- und Managementansätze, die bei früherer Erkennung bessere Erfolgsaussichten zeigen. Angesichts der Gefahr von Asthmaanfällen meiden viele Asthma-Patienten körperliche Anstrengung. Dies ist jedoch kontraproduktiv, da aktuelle Daten belegen, dass Bewegung gut verträglich ist und die Lebensqualität verbessert. Die Literatur, die sich für einen Nutzen von körperlicher Aktivität bei EIB ausspricht, ist gegenwärtig sehr positiv eingestellt, jedoch von äußerst begrenztem Umfang. Daher sollten zukünftige Forschungsbemühungen sich sowohl mit diesem Aspekt als auch mit der weiteren Erforschung der Pathophysiologie und der Mechanismen, die EIB und Asthma zugrunde liegen, befassen.
Auditory Responses to Vocal Sounds in the Songbird Nucleus Taeniae of the Amygdala and the Adjacent Arcopallium
Authors: Fujii Tomoko G. , Ikebuchi Maki , Okanoya Kazuo
Published: August 2016

Many species of animals communicate with others through vocalizations. Over time, these species have evolved mechanisms to respond to biologically relevant vocal sounds via adaptive behaviors. Songbirds provide a good opportunity to search for the neural basis of this adaptation, because they interact with others through a variety of vocalizations in complex social relationships. The nucleus taeniae of the amygdala (TnA) is a structure located in the ventromedial arcopallium, which is akin to the mammalian medial amygdala. Studies on the anatomy and function of this nucleus have led to the speculation that the TnA is one of the possible neural substrates that represents the relevance of acoustic stimuli related to behavior. However, neural responses in this nucleus to auditory stimuli have not been studied in depth. To give a detailed description about auditory responses of the TnA in the songbird, we conducted neural recordings from the TnA and the adjacent arcopallium in adult male and female Bengalese finches under anesthesia. The birds were exposed to auditory stimuli including natural vocalizations as well as synthesized noise. We demonstrated that a substantial population of neurons in the TnA and the adjacent arcopallium responded to vocal sounds and that some neurons were selectively activated to specific stimuli. Proportions of responsive cells and stimulus-selective cells were larger in males than in females. In addition, a larger ratio of selective cells was observed in the arcopallium compared to the TnA. These findings support the idea that neuronal activity in the TnA and the neighboring area represents behavioral relevance of sounds. Further studies in electrophysiology combined with evidence from other fields, such as region-specific gene expression patterns, are required to fully understand the functions of the TnA as well as the evolution of the amygdala in songbirds and vertebrate animals.
Retinal Ganglion Cell Topography and Retinal Resolution in the Baikal Seal (Pusa sibirica)
Authors: Mass Alla M. , Supin Alexander Y.
Published: August 2016

The total number, size, topographic distribution, and cell density of ganglion cells were studied in retinal wholemounts of Baikal seals (Pusa sibirica). The ganglion cell size varied from 10 to 38 μm. A distinct cell group consisted of large ganglion cells of more than 30 μm in diameter. The topographic distribution of ganglion cells showed a definite area of high cell density similar to the area centralis of terrestrial carnivores. This area was located approximately 6-7 mm dorsotemporally of the geometric center of the wholemount. In this area, the peak cell densities in two wholemounts were 3,800 and 3,400 cells/mm2 (mean 3,600 cells/mm2). With a posterior nodal distance of 24 mm (underwater), this density corresponds to 631 cells/square degree. These values predict a retinal resolution of 2.4′ in water and 3.0′ in air. The topographic distribution of large cells featured the highest density in the same location as the total ganglion cell population.
Radiofrequency Ablation of a Nonsustained Ventricular Tachycardia Arising from the Left Coronary Cusp of a Bicuspid Aortic Valve: A Case Report
Authors: Iliodromitis Konstantinos E. , Pastromas Sokratis , Tzeis Stylianos , Andrikopoulos George
Published: August 2016

Radiofrequency ablation is the therapy of choice for the suppression of medically intractable symptomatic ventricular arrhythmias. Here we present the case report of a 50-year-old woman with bicuspid aortic valve (BAV) and symptomatic nonsustained ventricular tachycardia arising from the left ventricular outflow tract (LVOT). The origin of the ventricular arrhythmia was confirmed in the left coronary cusp (LCC) of the BAV. The patient underwent a successful radiofrequency ablation. LCC of a tricuspid aortic valve is a common origin of idiopathic LVOT tachycardia; however, little is known for these types of arrhythmias when located in the cusps of a BAV.
Prenatal Inflammation, Infections and Mental Disorders
Authors: Flinkkilä Eerika , Keski-Rahkonen Anna , Marttunen Mauri , Raevuori Anu
Published: August 2016

Background: The objective of this descriptive review is to summarize the current scientific evidence on the effect of prenatal exposure to maternal infection and immune response on the offspring's risk for mental disorders (schizophrenia spectrum disorders, autism spectrum disorders, attention-deficit hyperactivity disorder, anorexia nervosa, and mood disorders). Sampling and Methods: Studies were searched from PubMed and Ovid MEDLINE (R) databases with the following keywords: ‘prenatal exposure delayed effects' and ‘infection', and ‘inflammation' and ‘mental disorders'. A comprehensive manual search, including a search from the reference list of included articles, was also performed. Results: Prenatal exposure to maternal influenza appears to increase the offspring's risk for schizophrenia spectrum disorders, although studies are not fully consistent. Prenatal exposure to maternal fever and elevated cytokine levels seems to be related to the elevated risk for autism spectrum disorders in the offspring. No replicated findings of an association between prenatal infectious exposure and other mental disorders exist. Conclusions: Evidence for the effect of prenatal exposure to maternal infection on risk for mental disorders exists for several different infections, suggesting that common factors occurring in infections (e.g. elevated cytokine levels and fever), rather than the infectious agent itself, might be the underlying factor in increasing the risk for mental disorders. Additionally, it is likely that genetic liability to these disorders operates in conjunction with the exposure. Therefore, genetically sensitive study designs are needed in future studies.
Antioxidative Stress Effects of Salvia przewalskii Extract in Experimentally Injured Podocytes
Authors: Liu Xiang , Liu Yun , Yang Yang , Xu Jiadai , Dai Deshu , Yan Chao , Li Xiangyang , Tang Renxian , Yu Chen , Ren Hongqi
Published: August 2016

Background: Oxidative stress is a leading cause of puromycin aminonucleoside (PAN)-induced nephrosis. As the inhibition of oxidative stress may improve injury of podocyte, we aimed at examining the effect of total phenolic acid extract of Salvia przewalskii (SPE) on PAN-induced oxidative stress in vivo and in vitro. Methods: Seventy-two male Sprague-Dawley rats were randomly assigned into 6 groups (n = 12), PAN alone, tacrolimus (TAC), SPE (50, 100 and 200 mg/kg) and normal control group. Salvianolic acid B (SalB, 5.52%) and rosmarinic acid (RA, 31.58%) were isolated from SPE. The intensities of 8-oxo-2'-deoxyguanosine (8-OHdG) were evaluated by immunofluorescence. In vitro, the podocytes were assigned into groups of control, PAN alone, TAC (1 μg/ml), SPE (158, 316 μg/ml), SalB (8.5, 17 μg/ml) and RA (25, 50 μg/ml). The intracellular reactive oxygen species (ROS) production and cell apoptosis rate were measured by flow cytometry. Form factor and aspect ratio were calculated to assess mitochondrial morphology. Results: In vivo, PAN increased the intensity of 8-OHdG in the renal tissue in the PAN group (p < 0.05). The high-dose SPE reduced 8-OHdG significantly at levels comparable to TAC alone (p > 0.05) on day 15. The intracellular ROS production, podocytes apoptosis rate and mitochondrial fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SalB significantly ameliorated the increase in the expression of ROS and revised the structure of mitochondria. The percentage of apoptotic cells was decreased compared with the PAN group after SPE, SalB, RA, and TAC treatment for 24 h (p < 0.05). Conclusion: These findings suggest that high-dose SPE significantly attenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SalB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SalB and RA can suppress PAN-induced apoptosis.
Sex Reversal in Birds
Authors: Major Andrew T. , Smith Craig A.
Published: August 2016

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal.
Exome Sequencing Fails to Identify the Genetic Cause of Aicardi Syndrome
Authors: Lund Caroline , Striano Pasquale , Sorte Hanne Sørmo , Parisi Pasquale , Iacomino Michele , Sheng Ying , Vigeland Magnus D. , Øye Anne-Marte , Steensbjerre Møller Rikke , Selmer Kaja K. , Zara Federico
Published: August 2016

Aicardi syndrome (AS) is a well-characterized neurodevelopmental disorder with an unknown etiology. In this study, we performed whole-exome sequencing in 11 female patients with the diagnosis of AS, in order to identify the disease-causing gene. In particular, we focused on detecting variants in the X chromosome, including the analysis of variants with a low number of sequencing reads, in case of somatic mosaicism. For 2 of the patients, we also sequenced the exome of the parents to search for de novo mutations. We did not identify any genetic variants likely to be damaging. Only one single missense variant was identified by the de novo analyses of the 2 trios, and this was considered benign. The failure to identify a disease gene in this study may be due to technical limitations of our study design, including the possibility that the genetic aberration leading to AS is situated in a non-exonic region or that the mutation is somatic and not detectable by our approach. Alternatively, it is possible that AS is genetically heterogeneous and that 11 patients are not sufficient to reveal the causative genes. Future studies of AS should consider designs where also non-exonic regions are explored and apply a sequencing depth so that also low-grade somatic mosaicism can be detected.
Changes in Body Mass Index in Girls with Idiopathic Central Precocious Puberty under Gonadotropin-Releasing Hormone Analogue Therapy: The Spanish Registry
Authors: Corripio Raquel , Soriano-Guillén Leandro , Herrero Francisco-Javier , Cañete Ramón , Castro-Feijoó Lidia , Escribano Aránzazu , Espino Rafael , Labarta José-Ignacio , Argente Jesús ,   The Spanish PUBERE Group
Published: August 2016

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI-SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached.
The Effects of Beta Amyloid Peptide 1-42 on Isolated Rat Hearts and Ileum Smooth Muscle
Authors: Yousefirad Neda , Kaygisiz Ziya , Aydin Yasemin
Published: August 2016

Neurotoxic beta amyloid peptides (βAPs) are involved in the pathogenesis of Alzheimer disease. βAP1-42 may also play a role in the regulation of cardiovascular functions. Therefore, we investigated the possible effects of βAP1-42 on isolated rat heart and ileum. The hearts were perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), maximal rate of pressure development of left ventricle (+dP/dtmax), heart rate, coronary flow, monophasic action potential amplitude (MAPamp), MAP duration at 90% repolarization (MAP90) and contractions of ileum were measured. One, 10 and 100 nmol/l doses of βAP1-42 significantly decreased LVDP, +dP/dtmax and heart rate. The dose of 1 nmol/l did not change coronary flow, but 10 and 100 nmol/l doses significantly reduced it. All doses of βAP1-42 did not alter MAPamp, but increased MAP90. βAP1-42 (1, 10, 100, 1,000 nmol/l) also did not influence ileum contractions. We suggest that βAP1-42 produces negative inotropic and negative chronotropic effects with an increase in MAP duration. Furthermore, βAP1-42 at high doses decreases coronary flow.
Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy
Authors: Xie Xinfang , Lv Jicheng , Shi Sufang , Zhu Li , Liu Lijun , Chen Min , Wang Yu , Cui Zhao , Wang Xin , Liu Li , Yu Xiaojuan , Zhou Fude , Zhao Ming-hui , Zhang Hong
Published: August 2016

Background: Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. Methods: Twelve patients with severe CreIgAN who received PE as addition to routine immunosuppressive therapy, followed for more than 6 months, were involved. Twelve matched historical controls who received immunosuppressive therapy alone were selected by propensity score matching. Renal survival, plasma IgA-IgG complex and active complement products were assessed. Results: Nine men and 3 women received a median of 7 PE courses (range 5-10). Their baseline urine protein excretion rate was 5.8 (4.5-8.7) g/day, and their serum creatinine level was 705.3 ± 296.4 μmol/l. During a mean follow-up of 15.6 months (6-51 months), 6 of the 12 PE group patients were free of dialysis, while all the control patients were dialysis dependent (6 of 12 vs. 0 of 12, p = 0.014). In the PE group, dialysis had to be restarted for 1 patient owing to the development of severe pneumonia and pulmonary failure. PE was associated with a higher kidney survival rate (log rank test, p = 0.026) during follow-up. It also significantly decreased plasma IgA-IgG complex levels (pre-PE: 85.3 ± 25.9% vs. post-PE: 38.4 ± 12.4%, p < 0.001) and plasma and urinary active complement product levels, including C3a, C5a and soluble C5b-9. The latter levels remained low until the last follow-up. Conclusion: This study indicated that PE could increase renal recovery rates in severe CreIgAN.
The burden of inhibitors in haemophilia patients
Authors: Walsh Christopher , Auerswald Guenter , Grancha Salvador , Jiménez-Yuste Victor
Published: August 2016

The burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors’, increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates.
How Brazilian students conceptualize the experience of learning German for academic purposes
Authors: Ferreira Luciane Corrêa
Published: August 2016

The present study aims to investigate how foreign language learners at the German for Academic Purposes (GAP) program at a Brazilian federal university interact in their mother tongue about their motivations to learn a foreign language as well as their motivations to participate in study abroad programs. Data were collected using focus group methodology with three focus groups of six students each (A1, A2 and B1 levels). We chose to analyze the A1 group. We conducted metaphor-led discourse analysis of the data in order to examine metaphors and metonymies, which emerged in the focus group interactions. We were able to identify the presence of systematic metaphors such as learning is hard work and learning is jumping hurdles, intertwined with conceptual metaphors such as education is a journey and difficulties are weights, which point at the motivation for learning verbalized by Brazilian foreign language learners who took part in the study
Odradek, inapprehensive chimera
Authors: Izabel Tomaz Amorim
Published: August 2016

Through the use of the idea of chimera, this essay will attempt to understand the open constitution of the character Odradek, from the short story “The cares of a family man” by Franz Kafka. What is interesting in this short story is the displacement (which includes the possibilities of gender expression in languages) Odradek imposes on the narrator’s constant effort (representing specific social groups) to categorize him/it and consequently the reader’s effort to enclose him/it in a closed interpretation. Odradek seems to be impossible to apprehend using main literary, biological or social categories which helped found of the idea of Modernity
Pelos bons serviços prestados e em razão do amor que lhe tenho: estratégias de luta dos escravos pela conquista da alforria em Rio Grande (1820-1860)
Authors: Souza Fernando Lucas Garcia de
Published: August 2016

Este artigo pretende discutir as estratégias utilizadas pelos escravos para alcançar a liberdade através da manumissão no município de Rio Grande, na Província de São Pedro do Rio Grande do Sul, entre os anos de 1820 a 1860. Para tanto, utilizamo-nos das fontes disponíveis no Acervo dos Tabelionatos de municípios do interior do Rio Grande do Sul e do diálogo com autores que discutem o tema em outras localidades no mesmo século.
Historiografia sobre o campo de estudos especializado na saúde dos escravos negros.
Authors: Eugênio Alisson
Published: August 2016

Este artigo apresenta e discute a Historiografia sobre o campo de estudos especializado na saúde dos escravos negros, com ênfase na produção norte-americana e, principalmente, a brasileira, para mostrar ao público interessado em tal campo de estudos o que foi produzido e as possibilidades de novas produções.
RESENHA: Literatura afro-brasileira: 100 autores do século XVIII ao XX, e Literatura afro-brasileira: abordagens na sala de aula.
Authors: Silva Mauricio
Published: August 2016

Impulsionado pela aprovação, há mais de dez anos, da lei 10.639 e pela visibilidade cada vez maior dos movimentos de valorização da matriz africana da cultura brasileira, os estudos acerca da produção literária afro-brasileira tem ganho, nos últimos anos, importância cada vez maior. É o que demonstra - entre outros exemplos - a recente publicação dos livros Literatura afro-brasileira: 100 autores do século XVIII ao XX e Literatura afro-brasileira: abordagens na sala de aula, ambos organizados pelo professor e pesquisador Eduardo de Assis Duarte.
Semiótica aplicada: campanha publicitária Journey, com Angelina Jolie, sob o espectro da teoria peirceana
Authors: Caraciola Carolina Boari
Published: August 2016

O presente artigo analisará uma peça da campanha publicitária Journey, da marca de luxo Louis Vuitton, estrelada pela atriz Angelina Jolie, sob o prisma da semiótica de extração peirceana. A análise da publicidade, sob o espectro da teoria semiótica, permite explicitar o potencial comunicativo do anúncio a que se refere, uma vez que as estratégias semióticas utilizadas por uma marca são fatores essenciais à sua constituição como marca, sendo, portanto, de fundamental importância para a compreensão de sua natureza, perfil e efeitos emocionais e funcionais.Palavras-chave: publicidade, semiótica peircena, luxo, Louis Vuitton.
Publicidad interrumpida: Análisis cultural de la comunicación publicitaria en internet
Authors: López Javier García , Hellín Ortuño Pedro A.
Published: August 2016

O objetivo deste artigo é analisar o processo de comunicação publicitária na Internet a partir de uma perspectiva cultural. Pesquisas recentes mostram que este tipo de publicidade gera uma comunicação com o receptor-consumidor caracterizada por golpes curtos, descoordenados e sobrepostos. Desde o método de argumentação filosófica prática vamos mergulhar em dissecar o processo de mudança de paradigma da publicidade para explicar como eles estão mudando processos de comunicação publicitária na Internet.
SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling
Authors: Kim Kangsan , Kim Il-Kug , Yang Jee Myung , Lee Eunhyeong , Koh Bong Ihn , Song Sukhyun , Park Junseong , Lee Sungsu , Choi Chulhee , Kim Jin Woo , Kubota Yoshiaki , Koh Gou Young , Kim Injune
Published: August 2016

Rationale:

Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined.

Objective:

To reveal the genetic interaction of Sox7, another Sox member, with Sox17 in developmental angiogenesis and their functional relationship with VEGF signaling.

Methods and Results:

Sox7 is expressed specifically in endothelial cells and its global and endothelial-specific deletion resulted in embryonic lethality with severely impaired angiogenesis in mice, substantially overlapping with Sox17 in both expression and function. Interestingly, compound heterozygosity for
Sox7
and
Sox17
phenocopied vascular defects of
Sox7
or
Sox17
homozygous knockout, indicating that the genetic cooperation of Sox7 and Sox17 is sensitive to their combined gene dosage. VEGF signaling upregulated both Sox7 and Sox17 expression in angiogenesis via mTOR pathway. Furthermore, Sox7 and Sox17 promoted VEGFR2 (VEGF receptor 2) expression in angiogenic vessels, suggesting a positive feedback loop between VEGF signaling and SoxF.

Conclusions:

Our findings demonstrate that SoxF transcription factors are indispensable players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.
Cardiovascular Risk in Hypertension in Relation to Achieved Blood Pressure Using Automated Office Blood Pressure Measurement
Authors: Myers Martin G. , Kaczorowski Janusz , Dolovich Lisa , Tu Karen , Paterson J. Michael
Published: August 2016

The SPRINT (Systolic Blood Pressure Intervention Trial) reported that some older, higher risk patients might benefit from a target systolic blood pressure (BP) of <120 versus <140 mm Hg. However, it is not yet known how the BP target and measurement methods used in SPRINT relate to cardiovascular outcomes in real-world practice. SPRINT used the automated office BP technique, which requires the patient to be resting quietly and alone, with multiple readings being recorded automatically using an electronic oscillometric sphygmomanometer. We studied the relationship between achieved automated office BP at baseline and cardiovascular events in 6183 community-dwelling residents of Ontario aged ≥66 years who were receiving antihypertensive therapy and followed for a mean of 4.6 years. Adjusted hazard ratios (95% confidence intervals) were computed for 10 mm Hg increments in achieved automated office BP at baseline using Cox proportional hazards regression and the BP category with the lowest event rate as the reference category. Based on 904 fatal and nonfatal cardiovascular events, the nadir of cardiovascular events was at the systolic pressure category of 110 to 119 mm Hg, which was lower than the next highest category of 120 to 129 mm Hg (hazard ratio 1.30 [1.01, 1.66]). The hazard ratio for diastolic pressure was relatively unchanged above 60 mm Hg. Pulse pressure exhibited an increase in hazard ratio (1.33 [1.02, 1.72]) at ≥80 mm Hg. These results using automated office BP measurement in a usual treatment setting extend the finding in SPRINT of an optimum target systolic BP of <120 mm Hg to routine clinical practice.
Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension
Authors: Dudenbostel Tanja , Ghazi Lama , Liu Mingchun , Li Peng , Oparil Suzanne , Calhoun David A.
Published: August 2016

Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension. A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with resistant hypertension has not been previously investigated. Our objective was to determine whether BMI is positively correlated with plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, and 24-hour urinary aldosterone in black and white patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with resistant hypertension. The relationship between plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, 24-hour urinary aldosterone, and BMI was investigated for the entire cohort, by sex and race (65.3% white, 40.3% men). We demonstrate that plasma aldosterone concentration and aldosterone:renin ratio were significantly correlated to BMI (
P
<0.0001) across the first 3 quartiles, but not from the 3rd to 4th quartile of BMI. Plasma renin activity was not correlated with BMI. Twenty-four–hour urinary aldosterone was positively correlated across all quartiles of BMI for the cohort (
P
<0.0001) and when analyzed by sex (men
P
<0.0001; women
P
=0.0013) and race (
P
<0.05), and stronger for men compared with women (
r
=0.19,
P
<0.001 versus
r
=0.05,
P
=0.431,
P
=0.028) regardless of race. In both black and white patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in black and white men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with resistant hypertension.
Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins
Authors: Caligiuri Stephanie P.B. , Rodriguez-Leyva Delfin , Aukema Harold M. , Ravandi Amir , Weighell Wendy , Guzman Randolph , Pierce Grant N.
Published: August 2016

In the year-long FlaxPAD clinical trial (Flaxseed for Peripheral Artery Disease), dietary flaxseed generated a powerful reduction in brachial systolic and diastolic blood pressure in patients with peripheral artery disease. Oxylipins were implicated as potential mechanistic mediators. However, the ability of flaxseed to impact central aortic hypertension, arterial stiffness, or cardiac performance was not investigated. Additionally, the relationship between central blood pressure (cBP) and oxylipins was not elucidated. Therefore, radial tonometry and pulse wave analysis were used to measure cBP and cardiac function in the FlaxPAD population (n=62). Plasma oxylipins were analyzed with high-performance liquid chromatography mass spectrometry. In patients with high blood pressure at baseline, the average decrease in central systolic and diastolic blood pressures versus placebo was 10 and 6 mm Hg, respectively. Flaxseed did not significantly impact augmentation index or other cardiac function indices. Alternatively, the data support several specific oxylipins as potential mediators in the antihypertensive properties of flaxseed. For example, every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid increased the odds of higher central systolic and diastolic blood pressures by 12- and 9-fold, respectively. Every 1 nmol/L increase in plasma thromboxane B
2
and 5,6-dihydroxyeicosatrienoic acid increased the odds of higher cBP by 33- and 9-fold, respectively. Flaxseed induced a decrease in many oxylipins, which corresponded with a reduced risk of elevated cBP. These data extend the antihypertensive properties of flaxseed to cBP without cardiac involvement but rather through oxylipins. This study provides further support for oxylipins as therapeutic targets in hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00781950.
Prescription of Guideline-Based Medical Therapies at Discharge After Carotid Artery Stenting and Endarterectomy
Authors: Aronow Herbert D. , Kennedy Kevin F. , Wayangankar Siddharth A. , Katzen Barry T. , Schneider Peter A. , Abou-Chebl Alex , Rosenfield Kenneth A.
Published: August 2016

Background and Purpose—

Carotid artery revascularization was previously found to incrementally reduce stroke risk among patients with carotid stenosis treated with medical therapy. However, the frequency with which optimal medical therapies are used at discharge after carotid endarterectomy (CEA) and carotid artery stenting (CAS) is not known, and the influence of patient, operator, and hospital characteristics on the likelihood of prescription is poorly understood.

Methods—

In a retrospective cohort study of 23 112 patients undergoing CAS or CEA between January 2007 and June 2012 at US hospitals participating in the CARE registry (Carotid Artery Revascularization and Endarterectomy), we examined antiplatelet therapy and statin utilization at discharge. Hierarchical multivariable logistic regression was used in adjusted analyses.

Results—

Antiplatelet agents and statins were prescribed at discharge in 99% and 78%, respectively, after CAS and 93% and 75%, respectively, after CEA. After adjustment, antiplatelet therapy was more often prescribed after CAS than CEA (odds ratio 2.4 [95% confidence interval 1.68–3.45]), but statin prescription was equally likely (odds ratio 1.11 [95% confidence interval 0.84–1.49]). Operator specialty (medical>radiology/surgery) and hospital community setting (suburban>urban>rural) independently predicted antiplatelet and statin agent use at discharge, whereas hospital geographic location (Northeast>Midwest/South>West) predicted use of statins but not antiplatelet therapy at discharge.

Conclusions—

US antiplatelet agent and statin discharge prescription rates were suboptimal after both CAS and CEA and varied by revascularization modality, operating physician specialty, and hospital characteristics. Improved and more uniform utilization after these procedures will be critical to the success of comprehensive stroke risk reduction efforts.