bluuebunny/crossref_metadata_2025 huggingface dataset:
Draft Genome Sequence of a Heterotrophic Facultative Anaerobic Thermophilic Bacterium, Ardenticatena maritima Strain 110S
T
Authors: Kawaichi Satoshi , Yoshida Takashi , Sako Yoshihiko , Nakamura Ryuhei
Published: October 2015

Ardenticatena maritima
strain 110S
T
is a filamentous bacterium isolated from an iron-rich coastal hydrothermal field, and it is a unique isolate capable of dissimilatory iron or nitrate reduction among the members of the bacterial phylum
Chloroflexi
. Here, we report the draft genome sequence comprising 3,569,367 bp, containing 3,355 predicted coding sequences (CDSs).
General practitioners’ attitudes towards the management of dental conditions and use of antibiotics in these consultations: a qualitative study
Authors: Cope Anwen L , Wood Fiona , Francis Nick A , Chestnutt Ivor G
Published: October 2015

Objectives

This study aimed to produce an account of the attitudes of general practitioners (GPs) towards the management of dental conditions in general practice, and sought to explore how GPs use antibiotics in the treatment of dental problems.

Design

Qualitative study employing semistructured telephone interviews and thematic analysis.

Participants

17 purposively sampled GPs working in Wales, of which 9 were male. The median number of years since graduation was 21. Maximum variation sampling techniques were used to ensure participants represented different Rural–Urban localities, worked in communities with varying levels of deprivation, and had differing lengths of practising career.

Results

Most GPs reported regularly managing dental problems, with more socioeconomically deprived patients being particularly prone to consult. Participants recognised that dental problems are not optimally managed in general practice, but had sympathy with patients experiencing dental pain who reported difficulty obtaining an emergency dental consultation. Many GPs considered antibiotics an acceptable first-line treatment for acute dental problems and reported that patients often attended expecting to receive antibiotics. GPs who reported that their usual practice was to prescribe antibiotics were more likely to prioritise patients’ immediate needs, whereas clinicians who reported rarely prescribing often did so to encourage patients to consult a dental professional.

Conclusions

The presentation of patients with dental problems presents challenges to GPs who report concerns about their ability to manage such conditions. Despite this, many reported frequently prescribing antibiotics for patients with dental conditions. This may contribute to both patient morbidity and the emergence of antimicrobial resistance. This research has identified the need for quantitative data on general practice consultations for dental problems and qualitative research exploring patient perspectives on reasons for consulting. The findings of these studies will inform the design of an intervention to support patients in accessing appropriate care when experiencing dental problems.
The UK Out of Hospital Cardiac Arrest Outcome (OHCAO) project
Authors: Perkins Gavin D , Brace-McDonnell Samantha J
Published: October 2015

Introduction

Reducing premature death is a key priority for the UK National Health Service (NHS). NHS Ambulance services treat approximately 30 000 cases of suspected cardiac arrest each year but survival rates vary. The British Heart Foundation and Resuscitation Council (UK) have funded a structured research programme—the Out of Hospital Cardiac Arrest Outcomes (OHCAO) programme. The aim of the project is to establish the epidemiology and outcome of OHCA, explore sources of variation in outcome and establish the feasibility of setting up a national OHCA registry.

Methods and analysis

This is a prospective observational study set in UK NHS Ambulance Services. The target population will be adults and children sustaining an OHCA who are attended by an NHS ambulance emergency response and where resuscitation is attempted. The data collected will be characterised broadly as system characteristics, emergency medical services (EMS) dispatch characteristics, patient characteristics and EMS process variables. The main outcome variables of interest will be return of spontaneous circulation and medium—long-term survival (30 days to 10-year survival).

Ethics and dissemination

Ethics committee permissions were gained and the study also has received approval from the Confidentiality Advisory Group Ethics and Confidentiality committee which provides authorisation to lawfully hold identifiable data on patients without their consent. To identify the key characteristics contributing to better outcomes in some ambulance services, reliable and reproducible systems need to be established for collecting data on OHCA in the UK. Reports generated from the registry will focus on data completeness, timeliness and quality. Subsequent reports will summarise demographic, patient, process and outcome variables with aim of improving patient care through focus quality improvement initiatives.
Clostridium perfringens type‐D enterotoxaemia in cattle: the diagnostic significance of intestinal epsilon toxin
Authors: Jones A. L. , Dagleish M. P. , Caldow G. L.
Published: October 2015

The aims of this study were to describe 42 cases of Clostridium perfringens type‐D enterotoxaemia in cattle seen between 2003 and 2014 and to determine the diagnostic value of detecting epsilon toxin in bovine intestinal content. All cases in the series had histological brain changes considered pathognomonic for C. perfringens type‐D enterotoxaemia in sheep and goats and the epsilon toxin of C. perfringens was concurrently detected in the intestinal contents of 15 (36 per cent) cases. The data from the case series indicate that intestinal epsilon toxin has a sensitivity of 56 per cent compared with histology of the brain for diagnosis of bovine C. perfringens type‐D enterotoxaemia. The diagnostic specificity of detecting epsilon toxin in bovine intestinal content was investigated by screening intestinal contents of 60 bovine carcases submitted for postmortem examination. Epsilon toxin was detected in 11 (18 per cent) carcases but no pathognomonic histological brain change was found in any. The specificity of intestinal epsilon toxin was estimated to be 80.4 per cent. These studies demonstrate that for a definitive diagnosis of C. perfringens type‐D enterotoxaemia in cattle histological examination of the brain is essential as the presence of epsilon toxin in the intestinal contents alone is neither sensitive nor specific enough.
Long‐term outcome of transendoscopic oesophageal mass ablation in dogs with Spirocerca lupi ‐associated oesophageal sarcoma
Authors: Shipov A. , Kelmer G. , Lavy E. , Milgram J. , Aroch I. , Segev G.
Published: October 2015

Oesophageal sarcoma is a potential sequel of Spirocerca lupi infection. Oesophageal mass excision can be performed by open chest surgery. The objectives of this observational study were to evaluate the feasibility, short‐term morbidity and long‐term outcome of transendoscopic oesophageal mass ablation in dogs with spirocercosis‐associated oesophageal neoplasia. A 9 mm video‐endoscope and laser or electrocauterisation were used to debulk the oesophageal mass. Long‐term follow‐up was done by telephonic interviews. Fifteen dogs were included. The median tumour size was 5 cm (range 3.5–9). The median procedure time was 75 minutes (range 35–165) and was deemed successful in 12/15 dogs (80 per cent). Recovery was uneventful in all dogs. Immediate complications included oesophageal damage (two dogs) oesophageal perforation (one dog) and a focal thermal damage (one dog). The median hospitalisation time of all dogs was less than one day, with all but two discharged on the procedure day. The median survival time, available in nine dogs that were followed, was 202 days (range 51–691). Four of these dogs (44 per cent) survived more than six months, of which three survived more than one year. In conclusion, transendoscopic oesophageal mass ablation might be considered an alternative, palliative procedure for open‐chest oesophageal surgery. It has comparable long‐term survival, lower morbidity, short hospitalisation time and relatively low cost.
Geology of the orogenic Cheminis gold deposit along the Larder Lake – Cadillac deformation zone, Ontario
Authors: Lafrance Bruno
Published: October 2015

The Larder Lake – Cadillac deformation zone (LLCDZ) is one of two major, auriferous, deformation zones in the southern Abitibi subprovince of the Archean Superior Province. It hosts the Cheminis and the giant Kerr Addison – Chesterville deposits within a strongly deformed band of Fe-rich tholeiitic basalt and komatiite of the Larder Lake Group (ca. 2705 Ma). The latter is bounded on both sides by younger, less deformed, Timiskaming turbidites (2674–2670 Ma). The earliest deformation features are F1 folds affecting the Timiskaming rocks, which formed either during D1 extensional faulting or during early D2 north–south shortening related to the opening and closure, respectively, of the Timiskaming basin. Continued shortening during D2 imbricated the older volcanic rocks and turbidites and produced regional F2 folds with an axial planar S2 cleavage. D2 deformation was partitioned into the weaker band of volcanic rocks, producing the strong S2 foliation, L2 stretching lineation, and south-side-up shear sense indicators, which characterize the LLCDZ. Gold is present in quartz–carbonate veins in deformed fuchsitic komatiites (carbonate ore) and turbiditic sandstone (sandstone-hosted ore), and in association with disseminated pyrite in altered Fe-rich tholeiitic basalts (flow ore). All host rocks underwent strong mass gains in CO2, S, K2O, Ba, As, and W, during sericitization, carbonatization, and sulphidation of the host rocks, suggesting that they interacted with the same hydrothermal fluids. Textural relationships between alteration minerals and S2 cleavage indicate that mineralization is syn-cleavage. Thus, gold was deposited as hydrothermal fluids migrated upward along the LLCDZ during contractional, D2 south-side-up shearing. The gold zones were subsequently modified during D3 reactivation of the LLCDZ as a dextral transcurrent fault zone.
Testing marine conservation applications of unmanned aerial systems (UAS) in a remote marine protected area
Authors: Brooke Samantha , Graham David , Jacobs Todd , Littnan Charles , Manuel Mark , O’Conner Robert
Published: October 2015

In 2014, the United States National Oceanic and Atmospheric Administration (NOAA) utilized unique partnerships with the National Aeronautics and Space Administration (NASA), and the US Coast Guard for the first comparative testing of two unmanned aircraft systems (UAS): the Ikhana (an MQ-9 Predator B) and a Puma All-Environment (Puma AE). A multidisciplinary team of scientists developed missions to explore the application of the two platforms to maritime surveillance and marine resource monitoring and assessment. Testing was conducted in the Papahānaumokuākea Marine National Monument, a marine protected area in the Northwest Hawaiian Islands. Nearly 30 h of footage were collected by the test platforms, containing imagery of marine mammals, sea turtles, seabirds, marine debris, and coastal habitat. Both platforms proved capable of collecting usable data, although imagery collected using the Puma was determined to be more useful for resource monitoring purposes. Lessons learned included the need for increased camera resolution, co-location of mission scientists and UAS operators, the influence of weather on the quality of imagery collected, post-processing resource demands, and the need for pre-planning of mission targets and approach to maximize efficiency.
Design and assessment of an acoustic ground cloak with layered structure
Authors: Xiong Jie , Chen Tianning , Wang Xiaopeng , Zhu Jian
Published: October 2015

In this paper, a two-dimensional acoustic ground cloak with alternating layered structure composed of mercury and water is designed on the basis of transformation acoustics and effective medium theory. The cloak exhibits excellent cloaking performance to hide an object from the detection of acoustic waves. Cosine similarity is proposed to precisely quantize and evaluate the cloaking performance, which turns out to be succinct and effective. Numerical simulations confirm that the cloak could work well in a broad frequency band in which the cloaking performance displays an oscillatory decrease with increasing frequency. In addition, the omnidirectional property, larger incident angle of the acoustic beam has the better cloaking performance, is analyzed. This multilayered structure of cloak may offer an access to fabrication simplicity and experimental demonstration. The concept of cosine similarity may be an enrichment of the assessment system for acoustic cloaks.
Optimization strategies with resource scarcity: From immunization of networks to the traveling salesman problem
Authors: Bellingeri Michele , Agliari Elena , Cassi Davide
Published: October 2015

The best strategy to immunize a complex network is usually evaluated in terms of the percolation threshold, i.e. the number of vaccine doses which make the largest connected cluster (LCC) vanish. The strategy inducing the minimum percolation threshold represents the optimal way to immunize the network. Here we show that the efficacy of the immunization strategies can change during the immunization process. This means that, if the number of doses is limited, the best strategy is not necessarily the one leading to the smallest percolation threshold. This outcome should warn about the adoption of global measures in order to evaluate the best immunization strategy.
Constraints on interacting dark energy from time delay lenses
Authors: Pan Yu , Cao Shuo , Li Li
Published: October 2015

We use the time delay measurements between multiple images of lensed sources in 18 strongly gravitationally lensed (SGL) systems to put additional constraints on three phenomenological interaction models for dark energy (DE) and dark matter (DM). The compatibility among the fits on the three models seems to imply that the coupling between DE and DM is a small value close to zero, which is compatible with the previous results for constraining interacting DE parameters. We find that, among the three interacting DE models, the [Formula: see text]IDE model with the interaction term [Formula: see text] proportional to the energy density of DM provides relatively better fits to recent observations. However, the coincidence problem is still very severe in the framework of three interacting DE models, since the fitting results do not show any preference for a nonzero coupling between DE and DM. More importantly, we have studied the significance of the current strong lensing data in deriving the interacting information between dark sectors, which highlights the importance of strong lensing time delay measurements to provide additional observational fits on alternative cosmological models.
On Simple Connectedness of Minimal Representation-Infinite Algebras
Authors: Yao Hailou , Han Guoqiang
Published: October 2015

Let A be a connected minimal representation-infinite algebra over an algebraically closed field k. In this paper, we investigate the simple connectedness and strong simple connectedness of A. We prove that A is simply connected if and only if its first Hochschild cohomology group H1(A) is trivial. We also give some equivalent conditions of strong simple connectedness of an algebra A.
Differential Graded Structures on Path Categories
Authors: Li Fang , Tan Dezhan
Published: October 2015

In this paper, we consider the graded path category associated to a quiver. We investigate all n-differentials on such a category, and also study the associated graded Lie algebra. Moreover, a necessary and sufficient condition is given for the graded path category to admit a DG category structure.
Semi-topological Galois Theory
Authors: Liao Hsuan-Yi , Teh Jyh-Haur
Published: October 2015

We introduce splitting coverings to enhance the well known analogy between field extensions and covering spaces. Semi-topological Galois groups are defined for Weierstrass polynomials and a Galois correspondence is proved. Combining results from braid groups, we solve the topological inverse Galois problem. As an application, symmetric and cyclic groups are realized over ℚ.
CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice
Authors: Riehl Terrence E. , Santhanam Srikanth , Foster Lynne , Ciorba Matthew , Stenson William F.
Published: October 2015

Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3–8 wk of age to wild-type, CD44−/−, and TLR4−/− mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5+ stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5+ reporter mice from postnatal day 7 to day 14 decreased Lgr5+ cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5+ stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4.
Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats
Authors: Zhang Linda S. , Sato Hirokazu , Yang Qing , Ryan Robert O. , Wang David Q.-H. , Howles Philip N. , Tso Patrick
Published: October 2015

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid ( n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate ( n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins.
Loss of NHE8 expression impairs intestinal mucosal integrity
Authors: Wang Aiping , Li Jing , Zhao Yang , Johansson Malin E. V. , Xu Hua , Ghishan Fayez K.
Published: October 2015

The newest member of the Na+/H+exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8−/−mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8−/−mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8−/−mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8−/−mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8−/−mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8−/−mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8−/−small intestinal crypt. The expression of enteric defensins was also decreased in NHE8−/−mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells.
Cardiovascular response to thermoregulatory challenges
Authors: Liu Cuiqing , Yavar Zubin , Sun Qinghua
Published: October 2015

A growing number of extreme climate events are occurring in the setting of ongoing climate change, with an increase in both the intensity and frequency. It has been shown that ambient temperature challenges have a direct and highly varied impact on cardiovascular health. With a rapidly growing amount of literature on this issue, we aim to review the recent publications regarding the impact of cold and heat on human populations with regard to cardiovascular disease (CVD) mortality/morbidity while also examining lag effects, vulnerable subgroups, and relevant mechanisms. Although the relative risk of morbidity/mortality associated with extreme temperature varied greatly across different studies, both cold and hot temperatures were associated with a positive mean excess of cardiovascular deaths or hospital admissions. Cause-specific study of CVD morbidity/mortality indicated that the sensitivity to temperature was disease-specific, with different patterns for acute and chronic ischemic heart disease. Vulnerability to temperature-related mortality was associated with some characteristics of the populations, including sex, age, location, socioeconomic condition, and comorbidities such as cardiac diseases, kidney diseases, diabetes, and hypertension. Temperature-induced damage is thought to be related to enhanced sympathetic reactivity followed by activation of the sympathetic nervous system, renin-angiotensin system, as well as dehydration and a systemic inflammatory response. Future research should focus on multidisciplinary adaptation strategies that incorporate epidemiology, climatology, indoor/building environments, energy usage, labor legislative perfection, and human thermal comfort models. Studies on the underlying mechanism by which temperature challenge induces pathophysiological response and CVD await profound and lasting investigation.
High-mobility group box 1 promotes extracellular matrix synthesis and wound repair in human bronchial epithelial cells
Authors: Ojo Oluwaseun O. , Ryu Min Hyung , Jha Aruni , Unruh Helmut , Halayko Andrew J.
Published: October 2015

High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) protein that binds Toll-like receptors (e.g., TLR4) and the receptor for advanced glycated end products (RAGE). The direct effects of HMGB1 on airway structural cells are not fully known. As epithelial cell responses are fundamental drivers of asthma, including abnormal repair-restitution linked to changes in extracellular matrix (ECM) synthesis, we tested the hypothesis that HMGB1 promotes bronchial epithelial cell wound repair via TLR4 and/or RAGE signaling that regulates ECM (fibronectin and the γ2-chain of laminin-5) and integrin protein abundance. To assess impact of HMGB1 we used molecular and pharmacological inhibitors of RAGE or TLR4 signaling in scratch wound, immunofluorescence, and immunoblotting assays to assess wound repair, ECM synthesis, and phosphorylation of intracellular signaling. HMGB1 increased wound closure, and this effect was attenuated by blocking RAGE and TLR4 signaling. HMGB1-induced fibronectin and laminin-5 (γ2 chain) was diminished by blocking RAGE and/or blunting TLR4 signaling. Similarly, induction of α3-integrin receptor for fibronectin and laminin-5 was also diminished by blocking TLR4 signaling and RAGE. Lastly, rapid and/or sustained phosphorylation of SMAD2, ERK1/2, and JNK signaling modulated HMGB1-induced wound closure. Our findings suggest a role for HMGB1 in human airway epithelial cell repair and restitution via multiple pathways mediated by TLR4 and RAGE that underpin increased ECM synthesis and modulation of cell-matrix adhesion.
Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation
Authors: Fakih Dalia , Pilecki Bartosz , Schlosser Anders , Jepsen Christine S. , Thomsen Laura K. , Ormhøj Maria , Watson Alastair , Madsen Jens , Clark Howard W. , Barfod Kenneth K. , Hansen Soren , Marcussen Niels , Jounblat Rania , Chamat Soulaima , Holmskov Uffe , Sorensen Grith L.
Published: October 2015

Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice ( Sftpd −/−) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd −/− and Sftpd +/+ mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd −/− mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.
Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis
Authors: Atochina-Vasserman Elena N. , Abramova Elena , James Melane L. , Rue Ryan , Liu Amy Y. , Ersumo Nathan Tessema , Guo Chang-Jiang , Gow Andrew J. , Krymskaya Vera P.
Published: October 2015

Pulmonary lymphangioleiomyomatosis (LAM), a rare progressive lung disease associated with mutations of the tuberous sclerosis complex 2 ( Tsc2) tumor suppressor gene, manifests by neoplastic growth of LAM cells, induction of cystic lung destruction, and respiratory failure. LAM severity correlates with upregulation in serum of the prolymphangiogenic vascular endothelial growth factor D (VEGF-D) that distinguishes LAM from other cystic diseases. The goals of our study was to determine whether Tsc2 deficiency upregulates VEGF-D, and whether axitinib, the Food and Drug Administration-approved small-molecule inhibitor of VEGF receptor (VEGFR) signaling, will reduce Tsc2-null lung lesion growth in a mouse model of LAM. Our data demonstrate upregulation of VEGF-D in the serum and lung lining in mice with Tsc2-null lesions. Progressive growth of Tsc2-null lesions induces recruitment and activation of inflammatory cells and increased nitric oxide production. Recruited cells isolated from the lung lining of mice with Tsc2-null lesions demonstrate upregulated expression of provasculogenic Vegfa, prolymphangiogenic Figf, and proinflammatory Nos2, Il6, and Ccl2 genes. Importantly, axitinib is an effective inhibitor of Tsc2-null lesion growth and inflammatory cell recruitment, which correlates with reduced VEGF-D levels in serum and lung lining. Our data demonstrate that pharmacological inhibition of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth, attenuates recruitment and activation of inflammatory cells, and reduces VEGF-D levels systemically and in the lung lining. Our study suggests a potential therapeutic benefit of inhibition of VEGFR signaling for treatment of LAM.
Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease
Authors: Wagenaar Gerry T. M. , Hiemstra Pieter S. , Gosens Reinoud
Published: October 2015

Supplemental oxygen after premature birth results in aberrant airway, alveolar, and pulmonary vascular development with an increased risk for bronchopulmonary dysplasia, and development of wheeze and asthma, pulmonary hypertension, and chronic obstructive pulmonary disease in survivors. Although stimulation of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway has significant beneficial effects on disease development in animal models, so far this could not be translated to the clinic. Oxidative stress reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in inactivation or degradation of sGC. Reduced sGC activity and/or expression is associated with pathology due to premature birth, oxidative stress-induced lung injury, including impaired alveolar maturation, smooth muscle cell (SMC) proliferation and contraction, impaired airway relaxation and vasodilation, inflammation, pulmonary hypertension, right ventricular hypertrophy, and an aggravated response toward hyperoxia-induced neonatal lung injury. Recently, Britt et al. (10) demonstrated that histamine-induced Ca2+ responses were significantly elevated in hyperoxia-exposed fetal human airway SMCs compared with normoxic controls and that this hyperoxia-induced increase in the response was strongly reduced by NO-independent stimulation and activation of sGC. These recent studies highlight the therapeutic potential of sGC modulators in the treatment of preterm infants for respiratory distress with supplemental oxygen. Such treatment is aimed at improving aberrant alveolar and vascular development of the neonatal lung and preventing the development of wheezing and asthma in survivors of premature birth. In addition, these studies highlight the suitability of fetal human airway SMCs as a translational model for pathological airway changes in the neonate.
High-intensity interval training-induced metabolic adaptation coupled with an increase in Hif-1α and glycolytic protein expression
Authors: Abe Takaaki , Kitaoka Yu , Kikuchi Dale Manjiro , Takeda Kohei , Numata Osamu , Takemasa Tohru
Published: October 2015

It is known that repeated bouts of high-intensity interval training (HIIT) lead to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in skeletal muscle; however, little is known about the molecular mechanisms underlying these adaptations. To decipher the mechanism leading to improvement of skeletal muscle glycolytic capacity associated with HIIT, we examined the role of hypoxia-inducible factor-1α (Hif-1α), the major transcription factor regulating the expression of genes related to anaerobic metabolism, in the adaptation to HIIT. First, we induced Hif-1α accumulation using ethyl 3,4-dihydroxybenzoate (EDHB) to assess the potential role of Hif-1α in skeletal muscle. Treatment with EDHB significantly increased the protein levels of Hif-1α in gastrocnemius muscles, accompanied by elevated expression of genes related to glycolysis, glycogenesis, and lactate transport. Daily administration of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius muscles. Second, we examined whether a single bout of HIIT could induce Hif-1α protein accumulation and subsequent increase in the expression of genes related to anaerobic metabolism in skeletal muscle. We observed that the protein levels of Hif-1α and expression of the target genes were elevated 3 h after an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of long-term HIIT. We found that long-term HIIT increased the basal levels of Hif-1α as well as the glycolytic capacity in gastrocnemius muscles. Our results suggest that Hif-1α is a key regulator in the metabolic adaptation to high-intensity training.
In vivo maximal fascicle-shortening velocity during plantar flexion in humans
Authors: Hauraix Hugo , Nordez Antoine , Guilhem Gaël , Rabita Giuseppe , Dorel Sylvain
Published: October 2015

Interindividual variability in performance of fast movements is commonly explained by a difference in maximal muscle-shortening velocity due to differences in the proportion of fast-twitch fibers. To provide a better understanding of the capacity to generate fast motion, this study aimed to 1) measure for the first time in vivo the maximal fascicle-shortening velocity of human muscle; 2) evaluate the relationship between angular velocity and fascicle-shortening velocity from low to maximal angular velocities; and 3) investigate the influence of musculo-articular features (moment arm, tendinous tissues stiffness, and muscle architecture) on maximal angular velocity. Ultrafast ultrasound images of the gastrocnemius medialis were obtained from 31 participants during maximal isokinetic and light-loaded plantar flexions. A strong linear relationship between fascicle-shortening velocity and angular velocity was reported for all subjects (mean R2 = 0.97). The maximal shortening velocity (VFmax) obtained during the no-load condition (NLc) ranged between 18.8 and 43.3 cm/s. VFmax values were very close to those of the maximal shortening velocity (Vmax), which was extrapolated from the F-V curve (the Hill model). Angular velocity reached during the NLc was significantly correlated with this VFmax ( r = 0.57; P < 0.001). This finding was in agreement with assumptions about the role of muscle fiber type, whereas interindividual comparisons clearly support the fact that other parameters may also contribute to performance during fast movements. Nevertheless, none of the biomechanical features considered in the present study were found to be directly related to the highest angular velocity, highlighting the complexity of the upstream mechanics that lead to maximal-velocity muscle contraction.
The Effect of Preserved Residual Renal Function on Left Ventricular Structure in Non-Anuric Peritoneal Dialysis Patients
Authors: Rebić Damir , Matovinović Mirjana Sabljar , Rašić Senija , Kes Petar , Hamzić-Mehmedbašić Aida
Published: October 2015

Background/Aims: Residual renal function (RRF) has been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between RRF and left ventricular hypertrophy (LVH) before switching on dialysis treatment and observed during 18 months on PD treatment. Methods: A prospective longitudinal study was performed in 50 non-anuric (defined as >200 mL urine output in a 24-hour period) PD patients. Echocardiography, RRF and other known risk factors for the increase of LV mass index (LVMi) were determined at study baseline and the end of follow-up. Results: There was 78% patients with LVH in end-stage renal disease (ESRD) baseline and 60% at the end of follow-up. RRF at the start of the study showed no significant difference between patients with normal and increased LVMi, as well as in daily collection of urine. After 18 months, patients with decreased LVMi had better RRF, lower CRP and better Kt/V compared to patients with increased LVMi (p < 0.001). Patients with better preserved RRF not only had significantly higher total Kt/V, but were less anemic and hypoproteinemic and lesser presence of LVH. Conclusions: PD in non-anuric ESRD patients the first 18 months has a positive effect on the preservation of RRF and partial regression of left ventricular remodeling.
Calcitonin Gene-Related Peptide Improves Hypoxia-Induced Inflammation and Apoptosis via Nitric Oxide in H9c2 Cardiomyoblast Cells
Authors: Duan Lixiao , Lei Han , Zhang Yi , Wan Biao , Chang Jing , Feng Qingping , Huang Wei
Published: October 2015

Objectives: The aim of this work was to investigate whether calcitonin gene-related peptide (CGRP) plays a protective role in cardiomyocytes against hypoxia-induced inflammation and apoptosis via an NO-mediated pathway. Methods: H9c2 cardiac cells were exposed to hypoxia for 2 h to establish a model of myocardial hypoxic-ischemic injury. The cells were pretreated with either CGRP or nitric oxide synthase (NOS) inhibitor (L-NAME) before being exposed to hypoxia for 30 min. Cell viability was analyzed using a cell counter kit 8 (CCK-8). The levels of IL-6 and TNF-α were determined by the corresponding enzyme-linked immunosorbent assay. The expression levels of several apoptosis proteins (p53, caspase-3, cytochrome C) and NOS were detected by Western blot assays. An NO kit was used to evaluate the production of NO. Results: Pretreatment of H9c2 cardiac cells with CGRP for 30 min prior to exposure to hypoxia markedly improved cell viability (83.57 ± 3.21 vs. 62.83 ± 8.30%, p < 0.001); the same effect was observed following pretreatment with the NOS inhibitor L-NAME (89.34 ± 5.95 vs. 75.01 ± 5.61%, p < 0.01). Pretreatment with CGRP also significantly attenuated the inflammatory responses induced by hypoxia, as evidenced by decreases of the levels of both IL-6 (193.21 ± 13.54 vs. 293.38 ± 56.49%, p < 0.001) and TNF-α (207.71 ± 44.27 vs. 281.46 ± 64.88%, p < 0.001). Additionally, CGRP significantly decreased the hypoxia-induced overexpression of the apoptotic proteins (p53: 0.27 ± 0.10 vs. 0.87 ± 0.30, p < 0.001; caspase-3: 0.65 ± 0.15 vs. 0.98 ± 0.26, p < 0.001; cytochrome C: 1.51 ± 0.39 vs. 2.80 ± 0.69, p < 0.001) and enhanced the expression of both endothelial NOS (eNOS; 0.59 ± 0.24 vs. 0.37 ± 0.14, p < 0.05) and phosphorylated eNOS (0.60 ± 0.13 vs. 0.40 ± 0.07, p < 0.05). Furthermore, the application of both L-NAME and CGRP attenuated the hypoxia-induced expression of inducible NOS (iNOS; p < 0.05) and enhanced a hypoxia-mediated decrease in NO (p < 0.01). Interestingly, the expression levels of cell apoptosis (p < 0.05), iNOS and eNOS (p < 0.05) were decreased with L-NAME and CGRP cotreatment following 2 h of acute hypoxia, but the apoptotic factors (p < 0.05) were increased compared with only CGRP pretreatment. Conclusion: CGRP protects cardiomyocytes from hypoxia-induced inflammation and apoptosis by modulating NO production.
The Role of Body Mass Index in Triple Negative Breast Cancer
Authors: Cakar Burcu , Muslu Ugur , Erdogan Atike P. , Ozisik Melih , Ozisik Hatice , Tunakan Dalgic Ceyda , Durusoy Raika , Karaca Burcak , Sezgin Canfeza , Karabulut Bulent , Uslu Ruchan
Published: October 2015

Background: Triple-negative breast cancer (TNBC) has none of the targeted treatment choices due to its distinct biological property, making this subtype a unique disease. In this study, we evaluated the impact of obesity on clinical outcomes of TNBC. Methods: The data of breast cancer patients admitted to our department were collected. TNBC was defined as lack of estrogen receptor (ER), progesterone receptor (PR) and HER-2. The body mass index (BMI) of 112 TNBC patients was calculated with weight at the time of diagnosis and height. The patients were classified into groups with a BMI of < 25 (normal/underweight), 25-29.9 (overweight) or ≥ 30 (obese). After a mean follow-up of 23.2 ± 15.5 months, there were 12 recurrences (10.71%) and 6 deaths (5.35%). Disease-free survival (DFS) and overall survival (OS) were assessed. Results: The survival analyses of all the patients did not demonstrate any differences in OS or DFS in obese as compared to non-obese patients. However, we showed that obesity was associated with a poorer OS for postmenopausal TNBC patients (p < 0.05). Conclusion: Obesity is related to a poorer OS in postmenopausal TNBC patients. Due to the heterogeneous disease profile of TNBC, larger randomized studies will be needed to clarify the exact role of obesity in TNBC.
The Gateway Hypothesis, Common Liability to Addictions or the Route of Administration Model? A Modelling Process Linking the Three Theories
Authors: Mayet Aurélie , Legleye Stéphane , Beck François , Falissard Bruno , Chau Nearkasen
Published: October 2015

Background: The aim of this study was to describe the transitions between tobacco (T), cannabis (C) and other illicit drugs (OIDs) initiations, to simultaneously explore several substance use theories: gateway theory (GT), common liability model (CLM) and route of administration model (RAM). Methods: Data from 2 French nationwide surveys conducted in 2005 and 2010 were used (16,421 subjects aged 18-34). Using reported ages at initiations, we reconstituted a retrospective cohort describing all initiation sequences between T, C and OID. Transition probabilities between the substances were computed using a Markov multi-state model that also tested the effect of 2 latent variables (item response theory scores reflecting propensity for early onset and further substance use) on all transitions. Results: T initiation was associated with increased likelihood of subsequent C initiation, but the reverse relationship was also observed. While the most likely initiation sequence among subjects who initiated the 3 groups of substances was the ‘gateway' sequence T → C → OID, this pattern was not associated with substance use propensity more than alternative sequences. Early use propensity was associated with the ‘gateway' sequence but also with some alternative ones beginning with T, C or OID. Conclusion: If the gateway sequence appears as the most likely pattern, in line with GT, the effects of early onset and substance use propensities were also observed for some alternative sequences, which is more in line with CLM. RAM could explain reciprocal interactions observed between T and C. This suggests shared influences of individual (personality traits) and environmental (substance availability, peer influence) characteristics.
Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi
Authors: Jongyotha Kamonchanok , Sriphrapradang Chutintorn
Published: October 2015

We report on a 79-year-old woman with staghorn calculi who presented with severe hypercalcemia. She was later found to have humoral hypercalcemia of malignancy caused by a rare tumor, squamous cell carcinoma of the renal pelvis. Chronic irritation, infection and inflammation from staghorn stones cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. The prognosis is very poor, with a 5-year survival rate of <10%. This case highlights the importance of awareness of a very rare and aggressive carcinoma in a patient with long-standing nephrolithiasis.
Susceptibilidade e resistência a antimicrobianos de Staphylococcus aureus em condições de biofilme
Authors: Chagas Laura Gonçalves da Silva , Melo Poliana De Castro , Lima Anna Monteiro Correia , Ramos Gabriela Bim , Röder Denise Von Dolinger de Brito , Nader-Filho Antônio
Published: October 2015

Os Staphylococcus, principais agentes causadores da mastite, quando em biofilmes, estão relacionados a uma série de mecanismos de resistência em diferentes tipos de infecções. O presente trabalho avaliou a susceptibilidade e resistência dos Staphylococcus aureus, isolados de casos de mastite bovina e do ambiente de ordenha, em condições de biofilme, frente a três antimicrobianos distintos em diferentes concentrações. Foram utilizadas trinta e duas estirpes de S. aureus testadas frente aos testes de inibição da concentração mínima de erradicação de biofilmes, utilizando cefalexina, amoxicilina e rifampicina, nas concentrações de 30 mg/mL, 50 mg/mL e 100 mg/mL, por doze horas de contato, e a eficiência dos testes avaliada pela contagem das unidades formadoras de colônias e pelo teste de microplacas. Os resultados revelaram que, entre os antimicrobianos testados, a cefalexina foi o que apresentou melhor eficiência nas três concentrações testadas, e a rifampicina e amoxacilina tiveram maior eficiência nas concentrações de 50 e 100 mg/ mL. Esses dados demonstram a importância sobre antibioticoterapia orientada associada com a correta higienização dos equipamentos de ordenha, evitando-se, assim, a formação de biofilmes, a adesão microbiana persistente em equipamentos, e a difusão dos microrganismos pelo canal ascendente dos tetos entre os animais do rebanho.
Waldomiro de Castro Santos Vergueiro
Authors: Almeida Marco Antonio De
Published: October 2015

Entrevista: Waldomiro de Castro Santos Vergueiro
Um olhar informacional para os mundos cultuais da internet
Authors: Méndez Héctor René Mena
Published: October 2015

Resenha de: 
KOZINETS, Robert V. Netnografia: realizando pesquisa etnográfica online. Porto Alegre: Penso, 2014. ISBN 978-85-65848-97-8.
Jornadas de Junho: uma leitura em quatro conceitos para a Ciência da Informação
Authors: Ferreira Rubens Da Silva
Published: October 2015

O trabalho tem como objetivo contribuir para o entendimento das manifestações recentes no Brasil, as chamadas Jornadas de Junho. Nesta direção, faz-se um exercício teórico de discussão no campo da Ciência da Informação, empregando os conceitos de informação, rede, afetos e multidão, precisamente para dar conta de uma realidade que se revela desconcertante para os governos, para a grande mídia, para os agentes econômicos e para a própria sociedade. De um modo geral, o trabalho aponta para o peso das redes digitais na construção de estratégias infocomunicativas, orientadas para a ação política de indivíduos e de grupos, seja nas ruas e/ou na Internet. Em seu conjunto, essas singularidades que se encontram nas manifestações dão forma a uma multidão que encontra força nas redes digitais, onde potencializam ações na perspectiva da luta por melhores condições de vida no país, expressando o sentido político da informação