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Glenn A Jacobson, Sharanne Raidal, Kate Robson, Christian K Narkowicz, David S Nichols, E Haydn Walters
BACKGROUND: Salmeterol (a long acting beta2-agonist) is a chiral molecule. (RR)-salmeterol is responsible for pharmacological effect, but basic knowledge of enantioselective pulmonary pharmacodynamics and pharmacokinetics of salmeterol remains unknown. There are safety concerns with (S)-enantiomers of beta2-agonists, with suggestions that these enantiomers may increase bronchial hyperresponsivneness in asthma patients. METHODOLOGY: Horses (n = 12) received racemic (rac-) salmeterol 250 μg via inhalation...
February 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
Charles S Fuchs, Toshihiko Doi, Raymond W Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia I Jalal, Manish A Shah, Jean-Phillipe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A Wainberg, Daniel V Catenacci, Atsushi Ohtsu, Kohei Shitara, Ravit Geva, Jonathan Bleeker, Andrew H Ko, Geoffrey Ku, Philip Philip, Peter C Enzinger, Yung-Jue Bang, Diane Levitan, Jiangdian Wang, Minori Rosales, Rita P Dalal, Harry H Yoon
Importance: Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. Objective: To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. Design, Setting, and Participants: In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016...
March 15, 2018: JAMA Oncology
Barbara Demmig-Adams, Jared J Stewart, Christopher R Baker, William W Adams
We review the role of a family of transcription factors and their regulons in maintaining high photosynthetic performance across a range of challenging environments with a focus on extreme temperatures and water availability. Specifically, these transcription factors include CBFs (C-repeat binding factors) and DREBs (dehydration-responsive element-binding), with CBF/DREB1 primarily orchestrating cold adaptation and other DREBs serving in heat, drought, and salinity adaptation. The central role of these modulators in plant performance under challenging environments is based on (i) interweaving of these regulators with other key signaling networks (plant hormones and redox signals) as well as (ii) their function in integrating responses across the whole plant, from light-harvesting and sugar-production in the leaf to foliar sugar export and water import and on to the plant's sugar-consuming sinks (growth, storage, and reproduction)...
March 15, 2018: International Journal of Molecular Sciences
Hongjia Zhang, Tan Sui, Enrico Salvati, Dominik Daisenberger, Alexander J G Lunt, Kai Soon Fong, Xu Song, Alexander M Korsunsky
High energy 2D X-ray powder diffraction experiments are widely used for lattice strain measurement. The 2D to 1D conversion of diffraction patterns is a necessary step used to prepare the data for full pattern refinement, but is inefficient when only peak centre position information is required for lattice strain evaluation. The multi-step conversion process is likely to lead to increased errors associated with the 'caking' (radial binning) or fitting procedures. A new method is proposed here that relies on direct Digital Image Correlation analysis of 2D X-ray powder diffraction patterns (XRD-DIC, for short)...
March 15, 2018: Materials
Sami M Aloush, Faris A Alsaraireh
OBJECTIVE:  To assess nurses' compliance with central line associated bloodstream infection (CLABSI) prevention guidelines related to maintenance of the central line and the predictors of compliance. Method: This was an observational study that used a descriptive cross-sectional design. A sample of 171 intensive care unit (ICU) nurses were observed and their compliance was recorded on a structured observational sheet. The study was conducted in the ICUs of 15 hospitals located in 5 cities in Jordan...
March 2018: Saudi Medical Journal
Afsha Aurshina, Anil Hingorani, Ahmad Alsheekh, Pavel Kibrik, Natalie Marks, Enrico Ascher
OBJECTIVE: It has been a widely accepted practice that a previous placed pacemaker, automatic implantable cardioverter defibrillators, or central line can be a contraindication to placing a hemodialysis catheter in the ipsilateral jugular vein. Fear of dislodging pacing wires, tunneling close to the battery site or causing venous obstruction has been a concern for surgeons and interventionalists alike. We suggest that this phobia may be unfounded. METHODS: A retrospective review was conducted of patients in whom hemodialysis catheters were placed over a period of 10 years...
March 1, 2018: Journal of Vascular Access
Peter Paik, Sanjay K Arukala, Anupam A Sule
Central venous catheters are placed in approximately five million patients annually in the US. The preferred site of insertion is one with fewer risks and easier access. Although the right internal jugular vein is preferred, on occasion, the left internal jugular may have to be accessed. A patient was admitted for septic shock, cerebrovascular accident, and non-ST-segment elevation myocardial infarction. A central venous line was needed for antibiotic and vasopressor administration. Due to trauma from a fall to the right side and previously failed catheterization attempts at the left subclavian and femoral veins, the left internal jugular vein was accessed...
January 9, 2018: Curēus
Tsutomu Namikawa, Kazune Fujisawa, Eri Munekage, Masaya Munekage, Yusuke Oki, Hiromichi Maeda, Hiroyuki Kitagawa, Hiroshi Ueta, Michiya Kobayashi, Kazuhiro Hanazaki
The present case report presents a rare case of Epstein-Barr virus (EBV)-associated early gastric carcinoma with lymphoid stroma, accompanied by lymph node metastasis. A 61-year-old woman was referred to our hospital following observation of a gastric mass lesion that was initially diagnosed at a medical check-up. Esophagogastroduodenoscopy revealed a slightly elevated lesion with a central irregular depression in the middle third of the stomach. Endoscopic ultrasonography revealed a well-circumscribed hypoechoic mass located predominantly within the submucosa and the mucosa...
April 2018: Molecular and Clinical Oncology
Carrie K Hui Mingalone, Zhiyi Liu, Judith M Hollander, Kirsten D Garvey, Averi L Gibson, Rose E Banks, Ming Zhang, Timothy E McAlindon, Heber C Nielsen, Irene Georgakoudi, Li Zeng
Osteoarthritis (OA) is a leading cause of chronic disability whose mechanism of pathogenesis is largely elusive. Local inflammation is thought to play a key role in OA progression, especially in injury-associated OA. While multiple inflammatory cytokines are detected, the timing and extent of overall inflammatory activities in early OA and the manner by which joint inflammation correlates with cartilage structural damage are still unclear. We induced OA via destabilization of the medial meniscus (DMM) in NFκB luciferase reporter mice, whose bioluminescent signal reflects the activity of NFκB, a central mediator of inflammation...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
Motoya Murase, Takumi Kawasaki, Rika Hakozaki, Takuya Sueyoshi, Dyaningtyas Dewi Pamungkas Putri, Yuichi Kitai, Shintaro Sato, Masahito Ikawa, Taro Kawai
TLRs recognize pathogen components and drive innate immune responses. They localize at either the plasma membrane or intracellular vesicles such as endosomes and lysosomes, and proper cellular localization is important for their ligand recognition and initiation of signaling. In this study, we disrupted ATP6V0D2, a component of vacuolar-type H+ adenosine triphosphatase (V-ATPase) that plays a central role in acidification of intracellular vesicles, in a macrophage cell line. ATP6V0D2-deficient cells exhibited reduced cytokine production in response to endosome-localized, nucleic acid-sensing TLR3, TLR7, and TLR9, but enhanced inflammatory cytokine production and NF-κB activation following stimulation with LPS, a TLR4 agonist...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release...
March 14, 2018: Journal of Neuroinflammation
Tiziana Alberio, Greta Forlani, Marta Lualdi, Giovanna Tosi, Roberto S Accolla, Mauro Fasano
BACKGROUND: Fibrinogen is a central player in the blood coagulation cascade and one of the most abundant plasma proteins. This glycoprotein also triggers important events (e.g., cell spreading, the respiratory burst and degranulation) in neutrophil cells via a αM β2 integrin-mediated binding to the cell surface. Yet, little is known about the interaction of fibrinogen with leukocytes other than neutrophils or stimulated monocytes, although high amounts of fibrinogen protein can also be found in lymphocytes, particularly in T-cells...
March 14, 2018: Journal of Translational Medicine
Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, John Bush, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro
BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs...
March 15, 2018: New England Journal of Medicine
Jessica MacLean, Tamara MacDonald, Carol Digout, Nadine Smith, Krista Rigby, Ketan Kulkarni
BACKGROUND: Central venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE). PROCEDURE: Case records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval...
March 14, 2018: Pediatric Blood & Cancer
Íñigo Corral, Susana Sainz de la Maza, Mario Rodríguez, Michal-Maciej Kawiorski, María-José López-Martínez, Juan-Carlos Galán
Neurological manifestations associated with HHV-7 have been described in primary infection in children, and very occasionally in immunocompromised adult patients. However, the role of HHV-7 reactivation as a cause of central nervous system (CNS) diseases in immunocompetent adults has not yet been defined. We retrospectively analyzed clinical and microbiological features of adults with neurological symptoms who underwent lumbar puncture and a multiplex polymerase chain reaction (PCR) for herpesviruses (HHV-1-8) and enteroviruses performed in cerebrospinal fluid (CSF), during a 4-year period...
March 13, 2018: Journal of Neurovirology
Jiaolong Shi, Fengping Li, Xingxing Yao, Tingyu Mou, Zhijun Xu, Zheng Han, Siyu Chen, Wende Li, Jiang Yu, Xiaolong Qi, Hao Liu, Guoxin Li
Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo...
March 14, 2018: Oncogene
Elise Allender, Harvinderjeet Deol, Sarah Schram, Kathleen J Maheras, Alexander Gow, Eleanor H Simpson, Fei Song
Neuregulin1 (NRG1) is a differentiation factor that regulates glial development, survival, synaptogenesis, axoglial interactions, and microglial activation. We previously reported that a targeted NRG1 antagonist (HBD-S-H4) given intrathecally, reduces inflammatory microglial activation in a spinal cord pain model and a neurodegenerative disease mouse model in vivo, suggesting that it may have effects in neuroninflammatory and neuronal disorders. We hypothesized that expression of HBD-S-H4 in the central nervous system (CNS) could reduce disease severity in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS)...
March 10, 2018: Journal of Neuroimmunology
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
Franklin R Toapanta, Paula J Bernal, Karen L Kotloff, Myron M Levine, Marcelo B Sztein
BACKGROUND: Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role...
March 13, 2018: Journal of Translational Medicine
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