bluuebunny/crossref_metadata_2025 huggingface dataset:
Method for synthesizing ZnO of different nanostructures by electrospinning and study of their gas sensing properties
Authors: Li Xiang-Bing , Ma Shu-Yi , Li Fu-Rong , Zhao Yu-Xiang , Liu Xiao-Bin , Lu Fei-Ping
Published: September 2019

The properties of nanomaterials usually depend on their microstructures, the same material of different microstructures could be used for various applications. However, most devices could only synthesize a single microstructure, so it is meaningful that the different microstructures were synthesized by one method. In our study, electrospinning was applied to fabricate ZnO nanofibers and nanoparticles. In this approach, Zn(Ac)/PVP composite fibers of different component ratio were synthesized by electrospinning method which was subsequently calcined and formed ZnO nanofibers and nanoparticles. The microstructure, chemical composition and gas sensing were investigated with scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and WS-60A gas sensing measurement system. The synthesis mechanisms of ZnO nanofibers and nanoparticles were discussed in detail.
Active Restricted Control for Harmonic Vibration Suppression
Authors: Wang Jiqiang
Published: September 2019

Active control systems are always restricted in one form or another. One of the restrictions is the lack of sensors or actuators for control implementation. This restricted control problem in the form of partial sensing and actuation thus poses a challenging problem for active controls, since most of the existing approaches make the implicit assumption that such information is readily available. This paper discusses the possibility of controlling structural vibration using restricted sensing and actuation control methodology. This opens a new avenue that, although counter to the current development in active control system designs through smart materials and smart structures, is readily applicable in practice. A number of fundamental results are derived concerning the active restricted controller properties, while algorithms are presented for the implementation. A case study is also provided, which demonstrates the feasibility of active restricted vibration control solutions.
MECHANICAL CHARACTERIZATION OF BRAIDED SELF-EXPANDING STENTS: IMPACT OF DESIGN PARAMETERS
Authors: ZHENG QINGLI , MOZAFARI HOZHABR , LI ZHIQIANG , GU LINXIA , AN MEIWEN , HAN XINWEI , YOU ZHONG
Published: September 2019

In this paper, the mechanical performance of braided nitinol stents was systematically studied to provide guidelines for optimum stent designs. The influences of braiding patterns, braiding angles, wire diameters, and strand numbers on the mechanical behavior of the stent in terms of crimping strain, radial strength, longitudinal flexibility, and stability were characterized utilizing finite element method. Our results have shown that the two key design factors of braided stents are the braiding angle and wire diameter. A smaller braiding angle can increase radial stiffness and have better longitudinal flexibility and can maintain the stent stability. The wire diameter has less influence on the radial stiffness than the braiding angle, but the longitudinal flexibility is most sensitive to the wire diameter. The strand number is directly proportional to the radial stiffness and inversely proportional to the longitudinal flexibility. Compared to the classical crossing pattern, we have also proposed two patterns. These patterns have a minimal impact on the crimping and radial stiffness of stents, but the stent made from them are more flexible. Among three crossing patterns, it is interesting to see that the classical pattern is the most stable crossing pattern for stand numbers larger than 36, but it became the most unstable pattern at the strand number of 24. This work has shed light on the optimum design of braided stents.
COMPUTATIONAL FLUID DYNAMICS MODELING OF PHARYNGEAL AIRWAY RESISTANCE BASED ON CONE-BEAM COMPUTED TOMOGRAPHY
Authors: PREMARAJ THYAGASEELY SHEELA , JU SIYEONG , PREMARAJ SUNDARALINGAM , KIM SUNG K. , GU LINXIA
Published: September 2019

Background: Oral appliances for treating patients with sleep related disorders such as snoring and disturbed sleep could alter the morphology of the pharyngeal airway and thus its flow dynamics as well as airway patency. Splint therapy, i.e., positioning the mandibular condyles in centric relation (CR) with maxillary anterior guided orthotics (MAGO), with regard to pharyngeal airway patency, is causing increased attention. The goal of this work is to quantitatively examine the fluid dynamic changes within the pharyngeal airway when the mandible is positioned in CR and its association with airway patency. Materials and Methods: Patient-specific computational fluid dynamics models were reconstructed from pre- and post- treatment high-resolution cone-beam computed tomography images for two patients who had undergone MAGO therapy. The minimal cross-sectional area and total volume of the pharyngeal airway were measured in the pre- and post-treatment for a total of four models. These two subjects were chosen out of 18 patients based on the airway volume changes in pre- and post-treatment. Subject 1 had a dramatic increase in the airway volume, whereas subject 2 kept a similar airway volume following the therapy. Both subjects anecdotally reported improvement in snoring, breathing and overall sleep quality. Results: We examined three parameters, i.e., the classically defined resistance of airway in terms of pressure drop, the minimal cross-sectional area, and the pharyngeal airway volume. We also proposed a new fluid dynamic parameter: the percentage area of higher vorticity, to be correlated with the clinical efficacy of the appliance for airway patency. All four parameters could be used as index factors for subject 1 to explain the measurable clinical outcomes and the subjective report regarding quality of breathing, snoring cessation, and improvement in sleep of the patient. But only the minimal cross-sectional area and percentage area of higher vorticity could explain the clinical observations and subjective outcome in subject 2 who reported similar effects after the treatment. Conclusion: Splint therapy expanded the minimal cross-sectional area in both subjects, but did not necessarily influence the pharyngeal airway volume. The airway shape changed in terms of the percentage area of higher vorticity and the minimal cross-sectional area. Further studies are needed to assess the clinical efficacy of MAGO in reducing or eliminating the sleep-related breathing difficulties and snoring.
COMPARISON OF THREE CONTROL STRATEGIES FOR AXIAL BLOOD PUMP
Authors: WU XIAO , ZHANG XIWEN , HAO PENGFEI , HE FENG
Published: September 2019

Facing the gradually increased prevalence of heart failure (HF) and the shortage of donated hearts, the blood pump is widely used to prolong the life of end-stage HF patients: however, the pump generates continuous flow under constant rotational speed, declining the arterial pulsatility and causing related complications. Previous studies show that synchronous copulsation might be the best control strategy for restoring pulsatility, but synchronous strategies are needed to monitor the phase of the heartbeat, which will make the controller complex and impair its robustness. Here, we compare constant speed, synchronous copulsation in a model of a cardiovascular system with a blood pump, which shows that copulsation offers more arterial pulsatility, less pump power-consumption, and thus better battery endurance, and constant speed offers a greater ventricular unloading effect. Meanwhile, we design a strategy based on transforming left ventricular pressure, which is easier to implement and has similar effect to synchronous copulsation.
Regurgitalites – a window into the trophic ecology of fossil cephalopods
Authors: Hoffmann R. , Stevens K. , Keupp H. , Simonsen S. , Schweigert G.
Published: September 2019

Fossil oral ejecta that exclusively contain bivalved calcitic lower jaws of ammonites (=aptychi) from Late Jurassic Solnhofen-type deposits of southern Germany are described. Based on the symphysis length of aptychi the ammonite shell diameters were reconstructed, ranging from 5 to 170 mm. To identify the potential ammonite predator published reports on stomach contents, coprolites and ammonite-palaeopathology were critically assessed. Implementation of the actualistic approach, together with some functional considerations, includes the identification of modern cephalopod predators with a focus on the modern
Nautilus
, and the distribution of vomiting behaviour among them. Stomach fluid pH is also important because species with an alkaline stomach pH are unable to dissolve calcareous hardparts and have to orally eject such material. Herein, we regard coleoids with an opportunistic diet as the most likely producers of the aptychi-bearing regurgitalites. This is based on finds of aptychi in the stomachs of the two coleoids
Plesioteuthis
and
Trachyteuthis.
They were likely fast, highly manoeuvrable swimmers. Both share a strong, triangular-shaped jaw apparatus that could possibly crush ammonite shells as well as arms equipped with suckers to hold their prey. Circumstantial evidence for coleoids as the producers comes from the alkaline pH of the stomach fluids of modern coleoids.

Supplementary material:
Data for lamellaptychi are available at
https://doi.org/10.6084/m9.figshare.c.4695002
Clinical value of non-coding RNAs in cardiovascular, pulmonary, and muscle diseases
Authors: Bonnet Sébastien , Boucherat Olivier , Paulin Roxane , Wu Danchen , Hindmarch Charles C. T. , Archer Stephen L. , Song Rui , Moore Joseph B. , Provencher Steeve , Zhang Lubo , Uchida Shizuka
Published: September 2019

Although a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA activity and protein function, knowledge of which has stimulated the expansion of a scientific field that quests to understand the role of ncRNAs in cellular physiology, tissue homeostasis, and human disease. Although our knowledge of these molecules has significantly improved over the years, we have limited understanding of their precise functions, protein interacting partners, and tissue-specific activities. Adding to this complexity, it remains unknown exactly how many ncRNAs there are in existence. The increased use of high-throughput transcriptomics techniques has rapidly expanded the list of ncRNAs, which now includes classical ncRNAs (e.g., ribosomal RNAs and transfer RNAs), microRNAs, and long ncRNAs. In addition, splicing by-products of protein-coding genes and ncRNAs, so-called circular RNAs, are now being investigated. Because there is substantial heterogeneity in the functions of ncRNAs, we have summarized the present state of knowledge regarding the functions of ncRNAs in heart, lungs, and skeletal muscle. This review highlights the pathophysiologic relevance of these ncRNAs in the context of human cardiovascular, pulmonary, and muscle diseases.
The fatty acid derivative palmitoylcarnitine abrogates colorectal cancer cell survival by depleting glutathione
Authors: Turnbull Patrick C. , Hughes Meghan C. , Perry Christopher G. R.
Published: September 2019

Previous evidence suggests that palmitoylcarnitine incubations trigger mitochondrial-mediated apoptosis in HT29 colorectal adenocarcinoma cells, yet nontransformed cells appear insensitive. The mechanism by which palmitoylcarnitine induces cancer cell death is unclear. The purpose of this investigation was to examine the relationship between mitochondrial kinetics and glutathione buffering in determining the effect of palmitoylcarnitine on cell survival. HT29 and HCT 116 colorectal adenocarcinoma cells, CCD 841 nontransformed colon cells, and MCF7 breast adenocarcinoma cells were exposed to 0 μM, 50 μM, and 100 μM palmitoylcarnitine for 24–48 h. HCT 116 and HT29 cells showed decreased cell survival following palmitoylcarnitine compared with CCD 841 cells. Palmitoylcarnitine stimulated H2O2 emission in HT29 and CCD 841 cells but increased it to a greater level in HT29 cells due largely to a higher basal H2O2 emission. This greater H2O2 emission was associated with lower glutathione buffering capacity and caspase-3 activation in HT29 cells. The glutathione-depleting agent buthionine sulfoximine sensitized CCD 841 cells and further sensitized HT29 cells to palmitoylcarnitine-induced decreases in cell survival. MCF7 cells did not produce H2O2 when exposed to palmitoylcarnitine and were able to maintain glutathione levels. Furthermore, HT29 cells demonstrated the lowest mitochondrial oxidative kinetics vs. CCD 841 and MCF7 cells. The results demonstrate that colorectal cancer is sensitive to palmitoylcarnitine due in part to an inability to prevent oxidative stress through glutathione-redox coupling, thereby rendering the cells sensitive to elevations in H2O2. These findings suggest that the relationship between inherent metabolic capacities and redox regulation is altered early in response to palmitoylcarnitine.
Involvement of high mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model
Authors: Maeda Ryo , Kawasaki Yukihiko , Kume Yohei , Go Hayato , Suyama Kazuhide , Hosoya Mitsuaki
Published: September 2019

Typical hemolytic uremic syndrome is caused by Shiga toxin (Stx2) and lipopolysaccharide (LPS) of Escherichia coli and leads to acute kidney injury. The role of innate immunity in this pathogenesis is unclear. We analyzed the role of high mobility group box 1 (HMGB1) at the onset of disease in a murine model. C57BL/6 mice were intraperitoneally administered saline ( group A), anti-HMGB1 monoclonal antibody ( group B), Stx2 and LPS to elicit severe disease ( group C), or Stx2, LPS, and anti-HMGB1 antibody ( group D). While all mice in group C died by day 5 of the experiment, all mice in group D survived. Anemia and thrombocytopenia were pronounced and plasma creatinine levels were significantly elevated in group C only at 72 h. While at 72 h after toxin administration the glomerulus tissue in group C showed pathology similar to that of humans, mesangial cell proliferation was seen in group D. Plasma HMGB1 levels in group C peaked 3 h after administration and were higher than those in other groups. Expression of the receptor of advanced glycation end products and NF-κB, involved in HMGB1 signaling, was significantly elevated in group C but not in group D. Administration of anti-HMGB1 antibody in a murine model of severe disease inhibited plasma HMGB1 and promoted amelioration of tissue damage. HMGB1 was found to be involved in the disease pathology; therefore, controlling HMGB1 activity might inhibit disease progression.
Analysis of the critical determinants of renal medullary oxygenation
Authors: Lee Chang-Joon , Gardiner Bruce S. , Evans Roger G. , Smith David W.
Published: September 2019

We have previously developed a three-dimensional computational model of oxygen transport in the renal medulla. In the present study, we used this model to quantify the sensitivity of renal medullary oxygenation to four of its major known determinants: medullary blood flow (MBF), medullary oxygen consumption rate (V̇o2,M), hemoglobin (Hb) concentration in the blood, and renal perfusion pressure. We also examined medullary oxygenation under special conditions of hydropenia, extracellular fluid volume expansion by infusion of isotonic saline, and hemodilution during cardiopulmonary bypass. Under baseline (normal) conditions, the average medullary tissue Po2 predicted for the whole renal medulla was ~30 mmHg. The periphery of the interbundle region in the outer medulla was identified as the most hypoxic region in the renal medulla, which demonstrates that the model prediction is qualitatively accurate. Medullary oxygenation was most sensitive to changes in renal perfusion pressure followed by Hb, MBF, and V̇o2,M, in that order. The medullary oxygenation also became sensitized by prohypoxic changes in other parameters, leading to a greater fall in medullary tissue Po2 when multiple parameters changed simultaneously. Hydropenia did not induce a significant change in medullary oxygenation compared with the baseline state, while volume expansion resulted in a large increase in inner medulla tissue Po2 (by ~15 mmHg). Under conditions of cardiopulmonary bypass, the renal medulla became severely hypoxic, due to hemodilution, with one-third of the outer stripe of outer medulla tissue having a Po2 of <5 mmHg.
Large gaze shift generation while standing: the role of the vestibular system
Authors: Anastasopoulos Dimitri , Ziavra Nausika , Bronstein Adolfo M.
Published: September 2019

The functional significance of vestibular information for the generation of gaze shifts is controversial and less well established than the vestibular contribution to gaze stability. In this study, we asked seven bilaterally avestibular patients to execute voluntary, whole body pivot turns to visual targets up to 180° while standing. In these conditions, not only are the demands imposed on gaze transfer mechanisms more challenging, but also neck proprioceptive input represents an inadequate source of head-in-space motion information. Patients’ body segment was slower and jerky. In the absence of visual feedback, gaze advanced in small steps, closely resembling normal multiple-step gaze-shift patterns, but as a consequence of the slow head motion, target acquisition was delayed. In ~25% of trials, however, patients moved faster but the velocity of prematurely emerging slow-phase compensatory eye movements remained lower than head-in-space velocity due to vestibuloocular failure. During these trials, therefore, gaze advanced toward the target without interruption but, again, taking longer than when normal controls use single-step gaze transfers. That is, even when patients attempted faster gaze shifts, exposing themselves to gaze instability, they acquired distant targets significantly later than controls. Thus, while patients are upright, loss of vestibular information disrupts not only gaze stability but also gaze transfers. The slow and ataxic head and trunk movements introduce significant foveation delays. These deficits explain patients’ symptoms during upright activities and show, for the first time, the clinical significance of losing the so-called “anticompensatory” (gaze shifting) function of the vestibuloocular reflex.

NEW & NOTEWORTHY Previous studies in sitting avestibular patients concluded that gaze transfers are not substantially compromised. Still, clinicians know that patients are impeded (e.g., looking side to side before crossing a road). We show that during large gaze transfers while standing, vestibularly derived head velocity signals are critical for the mechanisms governing reorientation to distant targets and multisegmental coordination. Our findings go beyond the traditional role of the vestibular system in gaze stability, extending it to gaze transfers, as well.
Hyaluronic Acid Binding to TLR4 Promotes Proliferation and Blocks Apoptosis in Colon Cancer
Authors: Makkar Sarbjeet , Riehl Terrence E. , Chen Baosheng , Yan Yan , Alvarado David M. , Ciorba Matthew A. , Stenson William F.
Published: September 2019

Hyaluronic acid (HA), a constituent of the extracellular matrix, promotes colorectal cancer growth. CD44 is a relevant HA receptor in this context. However, HA is also a ligand for TLR4, a receptor of significance in colorectal cancer. In this study, we examine the relative contribution of HA interactions with CD44 and TLR4 in colon tumorigenesis. Colorectal cancer models included ApcMin/+ mice, azoxymethane/dextran sodium sulfate (AOM-DSS), and CT26 tumor isografts. We used knockout mice and CT26 colorectal cancer cells with CRISPR knockdown of CD44 and TLR4. HA activity was modulated by PEP1 (a 12-mer peptide that blocks HA from binding its receptors), hyaluronidase (which promotes HA degradation), or 4-MU (HA synthesis inhibitor). Blockade of HA binding via PEP1 decreased growth in all colorectal cancer models and in cell culture. The effects were significant in WT and with CD44 deletion, but not with TLR4 deletion. In the AOM-DSS model, mice deficient in CD44 or TLR4 had fewer tumors. CD44- and TLR4-deficient CT26 isografts grew more slowly, exhibiting decreased tumor cell proliferation and increased apoptosis. In vitro, endogenous HA blocked LPS binding to TLR4 suggesting that HA is a relevant TLR4 ligand in colon cancer. Finally, PEP1 enhanced tumor radiation sensitivity in the isograft model. Together, these results indicate that HA binding to TLR4, as well as CD44, plays a key role in colon tumorigenesis. These findings also raise the possibility that an agent that blocks HA binding, such as PEP1, may be useful as an adjuvant therapy in colon cancer.
Fenretinide via NOXA Induction, Enhanced Activity of the BCL-2 Inhibitor Venetoclax in High BCL-2–Expressing Neuroblastoma Preclinical Models
Authors: Nguyen Thinh H. , Koneru Balakrishna , Wei Sung-Jen , Chen Wan Hsi , Makena Monish Ram , Urias Eduardo , Kang Min H. , Reynolds C. Patrick
Published: September 2019

Recurrent high-risk neuroblastoma is a childhood cancer that often fails to respond to therapy. Fenretinide (4-HPR) is a cytotoxic retinoid with clinical activity in recurrent neuroblastoma and venetoclax (ABT-199) is a selective inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2). We evaluated activity of 4-HPR + ABT-199 in preclinical models of neuroblastoma. Patient-derived cell lines and xenografts from progressive neuroblastoma were tested. Cytotoxicity was evaluated by DIMSCAN, apoptosis by flow cytometry, and gene expression by RNA sequencing, quantitative RT-PCR, and immunoblotting. 4-HPR + ABT-199 was highly synergistic against high BCL-2–expressing neuroblastoma cell lines and significantly improved event-free survival of mice carrying high BCL-2–expressing patient-derived xenografts (PDX). In 10 matched-pair cell lines [established at diagnosis (DX) and progressive disease (PD) from the same patients], BCL-2 expression in the DX and PD lines was comparable, suggesting that BCL-2 expression at diagnosis may provide a biomarker for neuroblastomas likely to respond to 4-HPR + ABT-199. In a pair of DX (COG-N-603x) and PD (COG-N-623x) PDXs established from the same patient, COG-N-623x was less responsive to cyclophosphamide + topotecan than COG-N-603x, but both DX and PD PDXs were responsive to 4-HPR + ABT-199. Synergy of 4-HPR + ABT-199 was mediated by induction of NOXA via 4-HPR stimulation of reactive oxygen species that induced expression of ATF4 and ATF3, transcription factors for NOXA. Thus, fenretinide + venetoclax is a synergistic combination that warrants clinical testing in high BCL-2–expressing neuroblastoma.
Exercise-Induced Changes in Ocular Blood Flow Parameters in Primary Open-Angle Glaucoma Patients
Authors: Gracitelli Carolina P.B. , de Faria Nubia Vanessa Lima , Almeida Izabela , Dias Diego Torres , Vieira Julia Maggi , Dorairaj Syril , Kanadani Fabio Nishimura , Prata Tiago Santos
Published: September 2019

Purpose: To evaluate exercise-induced changes in ocular blood flow (OBF) parameters in primary open-angle glaucoma (POAG) patients. Methods: A prospective observational study was carried out, in which medically treated patients with POAG were enrolled. Following inclusion, all patients performed a 40-min cycloergometry in a standardized fashion. The following parameters were measured and compared immediately before and 1 and 30 min after the exercise: intraocular pressure (IOP; Goldman applanation tonometry), mean arterial pressure (MAP), ocular pulse amplitude (OPA; assessed by dynamic contour tonometry), and ocular perfusion pressure (OPP; 2/3 MAP – IOP). In addition, we investigated possible factors associated with OBF parameter changes immediately after exercise. Results: A total of 30 eyes (30 patients; mean age was 62.9 ± 1.7 years) were included. Most patients were women (53%), and median visual field mean deviation index was –3.5 dB. Both MAP (mean change, 21%) and IOP (mean change, 17.3%) increased significantly immediately after the workout (p < 0.01), persisting higher than baseline following 30 min (p < 0.01%). Regarding OBF parameters, both OPA (mean change, 58.8%) and OPP (mean change, 21.7%) increased significantly immediately after the workout and persisted higher than baseline 30 min after the workout (p < 0.01). Regression analysis revealed that only age was significantly associated with OPA variation (R2 0.14; p < 0.05). No significant associations were found for OPP (p ≥ 0.19). Conclusion: Aerobic exercise leads to a significant short-time increase in OBF parameters in patients with POAG. Even though IOP seems to present a modest elevation, it is accompanied by a significant increase in MAP, leading to higher OBF measurements. Exercise-induced short-term changes and its possible implications for glaucoma prognosis deserve further investigation.
Endoscopic Tympanoplasty without Mastoidectomy for Active Mucosal Chronic Otitis Media with Mastoid and Tympanic Antrum Lesions: A Prospective Clinical Study
Authors: He Dan , Shou Zhu , Hsieh Yuelin , Wang Chengjin , Wang Jinyu , Han Zhao , Chi Fang-lu
Published: September 2019

Objective: This study aims to assess the effectiveness of endoscopic tympanoplasty without mastoidectomy in the management of active mucosal chronic otitis media (COM) patients with mastoid and tympanic antrum lesions. Methods: It is a prospective controlled study where 42 patients with active mucosal COM with mastoid and tympanic antrum lesions or normal aeration were recruited from the outpatient clinic of the otology department, Eye Ear Nose and Throat Hospital of Fudan University. All patients underwent endoscopic tympanoplasty without mastoidectomy by using the underlay technique with tragal cartilage graft with one side-perichondrium. The follow-up period was at least 3 months and results were evaluated in terms of graft uptake, ear dryness and hearing improvement. Results: Statistics showed no significant difference in graft uptake between the mastoid and tympanic antrum lesions group (90.5%) and the normal aeration group (95.2%). There was no significant difference in ear dryness between the mastoid and tympanic antrum lesions group (95.2%) and the normal aeration group (100%). Hearing improvement was comparable in the 2 groups. Conclusion: Regardless of the occurrence of soft density shadows in temporal bone showed by high-resolution computerized tomography in the mastoid and tympanic antrum, mastoidectomy is an unnecessary procedure for dealing with active mucosal COM without cholesteatoma. Therefore, this study shows that endoscopic tympanoplasty without mastoidectomy may be applied to active mucosal COM without cholesteatoma.
The Presence of Calcitonin Gene-Related Peptide and Its Receptors in Rat, Pig and Human Brain: Species Differences in Calcitonin Gene-Related Peptide Pharmacology
Authors: Warfvinge Karin , Edvinsson Lars , Pickering Darryl S. , Sheykhzade Majid
Published: September 2019

Aim: The aim of present study is to investigate the binding characteristics of non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists (i.e., gepants) in the brain membranes of rat, pig and human. Methods: The interaction of available gepants with the CGRP receptor was studied in the brain membranes of 3 different species using a radioligand competitive binding assay. In addition, the distribution of CGRP and its receptor component receptor activity modifying protein 1 (RAMP1) in rat cerebellum and cortex was explored using immunohistochemistry. Results: All gepants, except SB268262, displaced 100% of the radioligand specific binding in the brain tissue of all 3 species and showed highest affinity for CGRP receptors in human brain as compared to rat and pig brain membranes. Furthermore, radioligand binding studies revealed the presence of higher CGRP receptor density in human cerebellum compared to human cortex. The morphology, size and density of CGRP immunoreactive cells suggest that all cerebral cortical neurons were positive for CGRP. Slender receptor immunoreactive fibres were found spanning through the entire cortex. CGRP immunoreactivity was displayed in the cell soma of cerebellar Purkinje cells and in large neurons in the medial cerebellar nucleus. RAMP1 was found on the surface of the Purkinje cells and in parallel fibres, indicating presence in the granule cell axons. Conclusion: Cerebellum and cerebral cortex are rich in CGRP and CGRP receptors, which can be antagonized by gepants. However, all gepants display higher affinity for human CGRP receptors as compared to rat and pig CGRP receptors. Furthermore, human cerebellum seems to express higher density of CGRP receptors.
Piloting a Culturally Adapted Arabic Structured Small-Group Education Program for Adolescents with Type 1 Diabetes
Authors: Taha Nehad , Mesbah Naglaa , Rahme Zahra , Omar Dina , Sukkar Faten
Published: September 2019

Background:Kuwait has a high prevalence and incidence of type 1 diabetes (T1D). At present there is a need for structured educational programs (SEP) specifically tailored for Arabian youth with T1D. This SEP was locally and culturally adapted from the Kids In Control of Food (KICk-OFF) course delivered at the Dasman Diabetes Institute, Kuwait. Aims:To explore the psychological and social impact of a pilot SEP for Arabian youth with T1D and their mothers through exploring their respective perspectives. Methods:All 20 participants were interviewed using semistructured interviews individually, with a duration of approximately 30-45 min. The interviews were recorded and then transcribed verbatim. Data were analyzed using an inductive thematic approach. Results:The adolescents gained more self-confidence in managing their diabetes and their mothers were more confident in allowing their children take the lead in their diabetes self-management. Participants were empowered with adequate knowledge about the underlying pathophysiology of glucose metabolism and the nutritional and pharmacological management which made them feel in control and helped them to better cope with diabetes. It reduced diabetes-related family stress and gave them more social freedom, supporting behavioral change for a better lifestyle. Conclusions:Attending the adapted SEP had a positive impact on adolescents with T1D and their mothers through enhancement of their knowledge and confidence, thus giving them a sense of disease control. This pilot study has proven effective in terms of enhancement of confidence in diabetes management and psychosocial factors. Therefore, there is a need for a wider implementation.
Encenações da escrita nos textos de Adília Lopes
Authors: Kempinska Olga
Published: September 2019

Nos poemas e nas narrativas-fragmentos de Adília Lopes trata-se de um intenso convívio com a tessitura da morte e de um significativo deslocamento de sua representação do domínio consagrado pela tradição – o das flores, dos ossos e das conchas – para o âmbito dos materiais da escrita. E é justamente nesse deslocamento, que distancia a encenação da relação entre escrita e desejo do contexto da natureza, que consiste a singularidade dos textos da poeta portuguesa nos dias de hoje. Com efeito, a perturbadora confusão entre as posturas estética, prática e mágico-religiosa, delimitadas no âmbito do Círculo Linguístico de Praga por Jan Mukarovski, vê-se encenada em muitos dos textos de Adília Lopes que relatam fatos aparentemente corriqueiros, apontando para os perigos da pseudo-racionalidade totalitária. De fato, a renúncia ao caráter arbitrário do signo, típica da função mágica, é característica também de certos estados de um delírio psicótico que procura gratificações brutas para impulsos agressivos. Dessa forma, a denúncia do considerável enfraquecimento da eficácia da função estética em prol da função mágica, característica da superstição, torna-se o foco de sua exigente poética, na qual a lógica da metonímia e a referencialidade negativa se revelam instrumentos necessários da resistência subjetiva.
A promoção do português como língua global no século XXI
Authors: Mendes Edleise
Published: September 2019

A partir de uma perspectiva crítica e embasada nas discussões contemporâneas sobre a promoção das línguas em contextos multilíngues, discutirei o desenvolvimento e a expansão das políticas de promoção, projeção e difusão do português no mundo, com destaque nas políticas linguísticas desenvolvidas pelo Brasil no exterior, sobretudo no âmbito institucional. Para isso, analisarei os problemas e desafios enfrentados pelo país, em diferentes contextos de sua atuação, assim como discutirei iniciativas já realizadas e outras em curso. Finalmente, farei algumas considerações sobre os problemas e as perspectivas relativas à questão, considerando o cenário de promoção das línguas no século XXI. A partir da construção de uma nova gestão para o português, baseada na cooperação e no desenvolvimento de ações de âmbito transnacional, é possível desenharmos um cenário futuro no qual o português assegure o seu lugar em nosso século como uma das línguas de destaque no âmbito global.
Abstract 051: Oral Antihyperglycemic Therapy With a SGLT2 Inhibitor Reverses Cognitive Impairments in Elderly Diabetics
Authors: Wang Shaoxun , Fan Fan
Published: September 2019

Diabetes mellitus is a leading risk factor for aging-related dementia, but the underlying mechanisms by which long-standing hyperglycemia accelerates the loss of cognitive function are not fully elucidated. In the present study, we examined whether normalizing blood glucose and HbA1C levels with Luseogliflozin (20 mg/kg/day in drinking water for 4 months) can reverse cognitive impairments in old diabetic rats (18-month), and explored if this is related to the amelioration of cerebral vascular dysfunction seen in these rats. Plasma glucose and glycated hemoglobin levels fell from 392 ± 18 to 148 ± 7 mg/dL and 12 ± 0.2 vs. 6 ± 0.4% in old diabetic rats (n=12) after 4-month treatment with Luseogliflozin. Oral antihyperglycemic therapy did not alter body weight, blood pressure and protein excretion in these rats. We identified that impaired myogenic response in middle cerebral arteries (MCAs) observed in old diabetic rats was normalized after reducing plasma glucose levels with the SGLT2 inhibitor. Forced dilatation occurred at pressures > 140 mmHg in MCAs of elderly diabetic rats was rescued by normalization of plasma glucose. Cortical blood flow measured by laser Doppler flowmetry rose by 122 ± 19%, 41 ± 10%, 36 ± 4%, respectively, in old diabetic, SGLT2 inhibitor treated diabetic and non-diabetic rats when blood pressure was increased from 100 to 180 mmHg. Autoregulation of CBF was shifted to lower pressures in elderly diabetic rats and they exhibited breakthrough at pressures > 140 mmHg, while CBF autoregulation curve was shifted to the right after Luseogliflozin treatment in these rats. Normalization of plasma glucose with Luseogliflozin decreased reactive oxygen species (ROS) production in cerebral vessels by 50% to the same level as age-matched non-diabetic rats, improved endothelial function and rescued the impaired neurovascular coupling (NVC), blood-brain barrier (BBB) leakage and cognitive disabilities in old diabetic rats. These results provide the first evidence demonstrating that normalization of hyperglycemia with a SGLT2 inhibitor can reverse cerebrovascular dysfunction and cognitive impairments in the elderly with long-standing diabetes.
Abstract 064: Left Ventricular Mass Reduction Induced by Low Sodium Diet in Treated Hypertensive Patients
Authors: Musso Natale , Dotto Andrea , Shen Zhongyi
Published: September 2019

A first subset of 76 treated hypertensive patients (out of a larger group) concluded the analyses. These patients started a low sodium diet in the period 2016-2017. They had their BP, 24h urinary sodium (UNaV) and potassium (UKV) measured twice: before the diet was advised (time 1), and 2 months later (time 2); left ventricular mass (as LVMI) was measured at time 1 or shortly thereafter. Patients with UNaV reduction at time 2 were recalled after 2 years and had their BP, UNaV, UKV, and LVMI measured again (time 3).

Methods:
BP was recorded with the patient alone, in a seated position, with automatic repeated measures, by means of Omron 907 HEM monitors. LVED diameter, and IVS and PW thickness were evaluated by echocardiography and the usual Devereux’ formula was applied to calculate LVMI. UNaV and UKV were measured by commercial autoanalyzers.

Discussion:
a persistent compliance with the low sodium diet is seen in 53% of patients (40/76). In these patients we showed a significant decrease in LVMI, apparently related only to the urinary sodium. LVMI at the recall time (time 3) is not related to BP values, nor to the weight of our patients, nor to the amount of drugs employed. On the contrary, in patients who did not show a long time diet persistence, LVMI increased irrespective of BP, body weight or drug consumption. In the whole group and in the subgroups LVMI was significantly related to UNaV.

Conclusion:
in hypertensive patients with already a good pharmacologic control of their BP, the chronic habit of a low sodium diet can reduce the ventricular mass, measured as LVMI. This reduction seems not related to BP itself, nor to the body weight variation, nor to the drug consumption, but only to the sodium excretion.
Abstract 135: Cellular Senescence in the Paraventricular Nucleus - Novel Implications for Obesity-Induced Sympathoexcitation
Authors: Subramanian Madhan , Hall Delton , Balasubramanian Priya
Published: September 2019

Oxidative stress in the paraventricular nucleus (PVN) of the hypothalamus has been implicated in the pathogenesis of obesity-induced hypertension. Chronic oxidative stress is a known stimulus for induction of cellular senescence, a state of irreversible growth arrest in proliferating cells. Senescent cells are also a potential source of neuroinflammation as they secrete cytokines, chemokines and proteases through acquisition of senescence-associated secretory phenotype (SASP). Previous studies from our laboratory show evidence for cellular senescence in the rostral ventrolateral medulla (RVLM) of the brainstem in obesity. Whether obesity induces senescence in the PVN, an upstream driver of the RVLM to promote neuroinflammation and increases in SNA is not clear. Hence, we hypothesized that obesity triggers the induction of cellular senescence in the PVN, which in turn contributes to neuroinflammation and increases in SNA leading to the development of hypertension. To address this hypothesis, 2 months-old male C57BL/6J mice were fed a high-fat diet (HFD; 60% fat; n=4) or normal chow diet (Controls;10% fat; n=4) for 16 weeks. At the end of the dietary treatment, brains were isolated from the animals for assessment of senescence markers in the PVN. Data were analyzed by unpaired students t-test and expressed as mean±SE. HFD treatment significantly increased the mRNA expression levels of senescence marker p16
ink4a
(1.20±0.35 vs 3.76±0.67, fold change, normal diet vs HFD, p<0.05), which is a cyclin-dependent kinase inhibitor involved in inducing cell cycle arrest. This was accompanied with SASP characterized by increased expression levels of cytokines and chemokines, namely IL-1β (1.03±0.15 vs 1.80±0.21, p<0.05), IL-6 (1.01±0.08 vs 1.81±0.28, p<0.05), MCP1 (1.02±0.14 vs 2.45±0.09, p<0.05) and TNFα (1.09±0.11 vs 2.24±0.22, p<0.05) compared to controls. Beta-actin was used as the house keeping gene. Collectively, our results show for the first time, evidence for obesity associated cellular senescence in the PVN of the hypothalamus. In our next series of experiments, we plan to utilize p16 reporter mice to eliminate senescent cells and investigate the mechanistic role of senescence in the PVN in obesity-induced sympathoexcitation.
Abstract 141: Enhanced Hydrogen Peroxide-Dependent Renin and Pro-Renin Release in Juxtaglomerular Cells from Diabetic Mice: Role of NOX1
Authors: Ortiz-Capisano M. Cecilia , Maskey Dipak , Mendez Mariela
Published: September 2019

A large fraction of patients with diabetes mellitus develop diabetic nephropathy and are hypertensive. The Akita mice is one of the few mouse models of diabetes mellitus with features of the human disease including hypertension and kidney damage. Previous data showed increased levels of reactive oxygen species in the kidneys of Akita mice. We found that hydrogen peroxide (H
2
O
2
) is a potent stimulus for renin release from the juxtaglomerular (JG) cells
in vitro
and
in vivo
. Plasma pro-renin levels are elevated in diabetic patients and thought to contribute to hypertension and renal damage. Thus, we hypothesized that H
2
O
2
levels are higher in JG cells from Akita mice leading to increased renin and pro-renin release in diabetes. We measured H
2
O
2
by transducing primary cultures of JG cells with the fluorescent protein H
2
O
2
sensor Hyper, under control of the renin1 promoter. JG cells isolated from Akita mice had higher baseline levels of H
2
O
2
(C57= 100, Akita=222.5±79%,
p
<0.05). We also found that pro-renin expression was higher in JG cells from Akita by 79±21% (
p
<0.05). In addition, JG cells from Akita mice have higher pro-renin (n=4;
p
<0.05) and renin (C57= 100, Akita=219.2±26%;
p
<0.04, n=6) release to the media when compared to JG cells from C57. Western Blots showed that the NADPH oxidase isoform NOX1 is upregulated in JG cells from Akita mice (C57=100%; Akita=147±10%; n=4;
p
<0.05), whereas NOX2 or NOX4 were not different. NOX1 co-localized with renin-containing granules in kidney sections analyzed by confocal microscopy (n=4). Silencing NOX1 in JG cells from Akita mice decreased renin release to C57 control levels; (n=6;
p
<0.01) while silencing NOX4 had no effect (n=6). Expression of Catalase, which scavenges H
2
O
2
, was reduced in JG cells from Akita mice (C57=100%; Akita= 36±9.2%; n=4;
p
<0.05) and overexpression of Catalase in JG cells from Akita decreased baseline renin release by 35±8% (
p
<0.05). We conclude that renin cells from diabetic Akita mice have higher endogenous H
2
O
2
leading to increased renin and pro-renin release
via
enhanced NOX1 expression and decreased catalase. Enhanced H
2
O
2
-dependent renin release in Akita JG cells could be involved in renal damage and hypertension in diabetes mellitus.
Abstract P132: Differential and Sex Dependent Expression of Vasopressin Receptors by B Cells, NK Cells, and Dendritic Cells
Authors: Scroggins Sabrina M , Sharp Lydia E , Lund Jenna M , Devor Eric J , Warrier Akshaya , Hamilton Wendy S , Santillan Donna A , Santillan Mark K
Published: September 2019

Arginine vasopressin (AVP) has been shown to play a role in preeclampsia, a hypertensive and immune-mediated disorder in pregnancy. Chronic infusion of AVP during gestation into wild-type mice results in the pregnancy-specific physiological changes (hypertension, kidney damage, fetal growth restriction) as well as increased CD4+ T
H
1 and T
H
17 associated cytokine responses observed in human pregnancies affected by preeclampsia. Further, human CD4+ T cells isolated from preeclamptic women were found to differentially express AVP receptors (AVPRs) 1a and 2 compared to control pregnancies. Abnormalities in other immune cells are seen during preeclampsia, including auto-antibody production (B cells), poor placental development (natural killer (NK) cells), and increased pro-inflammatory T cells responses (via dendritic cells (DC)). We, therefore, hypothesize that B cells, NK cells, and DC express AVPRs. To begin to understand 1) the expression pattern of AVPRs on CD4- lymphocytes and 2) if there are differences in expression between males and females, we evaluated the expression of AVPR 1a, 2, and 1b specifically on B cells, NK cells, and DC. Each subset was purified via negative selection from de-identified human peripheral blood mononuclear cells obtained through Leukocyte Reduction System (LRS) cone donors at the DeGowin Blood Center followed by qPCR for AVPR 1a, 2, and 1b expression (N=6 per cell type). B cells, NK cells, and DC expressed all three AVPRs 1a, 2, and 1b. All three lymphocyte populations showed a lower expression of AVPR1b compared to expression of 1a and 2, with B cells having the lowest expression of AVPR1b (p<0.05). Interestingly, while B cells and NK cells showed no differences in expression based on sex of the donor, DC isolated from male donors more highly expressed AVPR1b compared to female donors (p=0.0035). In conclusion, we demonstrate that B cells, NK cells, and DC highly express AVPR1a and 2, and that DC expression of AVPRs is sex dependent. Further investigation into the utilization of these receptors by these immune cells and the potential impact of sex-specific differences may elucidate newly identified mechanisms of AVP and immune interactions in not only preeclampsia, but possibly other cardiovascular-related diseases as well.
Abstract P187: Incidence and Predictors of Diuretic-Induced Hyponatremia
Authors: Matanes Faris , Siddiqui Mohammed , Dudenbostel Tanja , Calhoun David , Oparil Suzanne
Published: September 2019

Hyponatremia is a common adverse effect of diuretic use. The purpose of this study was to determine the incidence of Diuretic-induced hyponatremia (DIH) (serum sodium <133mEq/L) caused by commonly used diuretics for treatment of hypertension, specifically, chlorthalidone, hydrochlorothiazide and spironolactone. Electronic health records of outpatients seen at UAB over the last 3 years were reviewed. Inclusion criteria included treatment with one or more of the above mentioned diuretics and having normal sodium levels before and after the hyponatremic episode. Exclusion criteria included heart failure, liver cirrhosis, adrenal insufficiency or an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73 m2. The cohort constituted of 270 patients. Based on the total number of prescriptions for each medication, the incidence of DIH was 3.6% for chlorthalidone (48 out of 1322), 3% for spironolactone (35 out of 1159), 1.7% for hydrochlorothiazide (178 out of 10660), while 9 developed hyponatremia on 2 diuretics. Only 57 patients normalized sodium levels after discontinuation of the diuretic, while 213 had normalization of sodium levels despite continuation of the diuretic. Individuals whose sodium levels returned to normal after the diuretic was stopped had lower sodium levels during the hyponatremic episode compared to those who continued the diuretic (129.3±3.9 vs. 130.4±2.0, p=0.002). Older age, Caucasian race, lower baseline sodium levels and lower eGFR values were all risk factors for developing DIH. In this retrospective study, 79% of the patients who developed hyponatremia on diuretics had normalization of serum sodium levels without stopping the diuretic.