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Pirow Bekker, Daniel Dairaghi, Lisa Seitz, Manmohan Leleti, Yu Wang, Linda Ertl, Trageen Baumgart, Sarah Shugarts, Lisa Lohr, Ton Dang, Shichang Miao, Yibin Zeng, Pingchen Fan, Penglie Zhang, Daniel Johnson, Jay Powers, Juan Jaen, Israel Charo, Thomas J Schall
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood...
2016: PloS One
Yuheng Wang, Konstantin von Gunten, Barbora Bartova, Nicolas Meisser, Markus Astner, Mario Burger, Rizlan Bernier-Latmani
Hundreds of tons of depleted uranium (DU) ammunition were used in previous armed conflicts in Iraq, Bosnia and Herzegovina and Serbia/Kosovo. The majority (>90%) of DU penetrators miss their target and, if left in the environment, corrode in these post-conflict zones. Thus, the best way to understand the fate of bulk DU material in the environment is to characterize the corrosion products of intact DU penetrators under field conditions for extended periods of time. However, such studies are scarce. To fill this knowledge gap, we characterized corrosion products formed from two intact DU penetrators that remained in soils in Bosnia and Herzegovina for over seven years...
October 21, 2016: Environmental Science & Technology
Cristina Rodríguez, Tomás Sobrino, Jesús Agulla, Verónica Bobo-Jiménez, María E Ramos-Araque, Juan J Duarte, José C Gómez-Sánchez, Juan P Bolaños, José Castillo, Ángeles Almeida
Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein...
October 21, 2016: Cell Death and Differentiation
Vishnu Priya Bollampalli, Susanne Nylén, Antonio Gigliotti Rothfuchs
Dendritic cells (DCs) are important for initiating immune responses, in part through their ability to acquire and shuttle antigen to the draining lymph node (DLN). The mobilization of DCs to the DLN is complex and remains to be fully elucidated during infection. Herein described is the use of an innovative, simple assay that relies on the fluorochrome 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track the migration of DCs during footpad infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG) in C57BL/6 mice...
October 9, 2016: Journal of Visualized Experiments: JoVE
Patrícia Napoleão, Teresa Freitas, Carlota Saldanha
AIMS: Oxidized low density lipoprotein (ox-LDL) has been reported as an inhibitor of nitric oxide (NO)-mediated dilatation in microcirculation. Oxidized LDL effect on NO metabolism of erythrocytes is not known. Therefore, this study aims to evaluate the effect of ox-LDL on erythrocytes NO metabolism. METHODS: The effect of different concentrations of human purified ox-LDL (25, 50 and 100 μg/mL) on NO metabolism was evaluated on blood of healthy subjects. RESULTS: An inhibitory effect of higher concentrations of ox-LDL on erythrocyte NO efflux levels was verified...
October 20, 2016: Clinical Hemorheology and Microcirculation
Scott Seaman, Paul Nelson, Jacob Alexander, Andrew Swift, James Fick
The authors present the case of a 53-year-old man who was referred with disabling retching provoked by left arm abduction. At the time of his initial evaluation, a cervical MRI study was available for review and revealed an anatomical variation of the ipsilateral juxtamedullary vertebrobasilar junction. After brain imaging revealed contact of the medulla by a dolichoectatic vertebral artery at the dorsal root entry zone of the glossopharyngeal and vagus nerves, the patient was successfully treated by microvascular decompression of the brainstem and cranial nerves...
October 21, 2016: Journal of Neurosurgery
Vivian M Nguyen, Nathan Young, Steven J Cooke
Scholars across all disciplines have long been interested in how knowledge moves within and beyond their community of peers. In conservation and natural resource management, however, we are lagging behind. Rapid environmental changes and calls for sustainable management practices mean that we urgently need to be using the best knowledge possible in forming decisions, policies, and practices to protect biodiversity and sustainably manage vulnerable natural resources. While the conservation literature on knowledge exchange (KE) and knowledge mobilization (KMb) has grown in recent years, much of it is based on context-specific case studies...
October 21, 2016: Conservation Biology: the Journal of the Society for Conservation Biology
Elisa C K Steinfurth, Manuela G Alius, Julia Wendt, Alfons O Hamm
The current experiments tested neural and physiological correlates of worry and rumination in comparison to thinking about neutral events. According to the avoidance model-stating that worry is a strategy to reduce intense emotions-physiological and neurobiological activity during worried thinking should not differ from activation during neutral thinking. According to the contrast avoidance model-stating that worry is a strategy to reduce abrupt shifts of emotions-activity should be increased. To test these competing models, we induced worry and neutral thinking in healthy participants using personal topics...
October 21, 2016: Psychophysiology
Geeta Shroff, Dipin Thakur, Varun Dhingra, Deepak Singh Baroli, Deepanshu Khatri, Rahul Dev Gautam
BACKGROUND: The major complication faced by patients with chronic static spinal cord injury (SCI) is the loss of mobilization. With the aim to rehabilitate SCI patients, physiotherapy is performed worldwide. However, it only helps the patients to live with their disabilities. An interdisciplinary management involving human embryonic stem cell (hESC) therapy along with physiotherapy as a supportive therapy offers regenerative treatment of the patients with SCI. MAIN BODY: The present study focuses on the role of physiotherapy in the mobilization of patients with SCI (paraplegic 136; tetraplegics 90) undergoing hESC therapy...
December 2016: Clinical and Translational Medicine
Muhammad Rafehi, Joachim C Burbiel, Isaac Y Attah, Aliaa Abdelrahman, Christa E Müller
The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties...
October 20, 2016: Purinergic Signalling
Casey T Clark, Alyson H Fleming, John Calambokidis, Nicholas M Kellar, Camryn D Allen, Krista N Catelani, Michelle Robbins, Nicole E Beaulieu, Debbie Steel, James T Harvey
Understanding reproductive rates of wild animal populations is crucially important for management and conservation. Assessing pregnancy status of free-ranging cetaceans has historically been difficult; however, recent advances in analytical techniques have allowed the diagnosis of pregnancy from small samples of blubber tissue. The primary objectives of this study were as follows: (i) to test the efficacy of blubber progesterone assays as a tool for diagnosing pregnancy in humpback whales (Megaptera novaeangliae); (ii) to estimate the pregnancy rate of humpback whales in Monterey Bay, California; and (iii) to investigate the relationship between stable isotopes and reproductive status of these whales...
2016: Conservation Physiology
Giovanni Bernardini, Fabrizio Antonangeli, Valentina Bonanni, Angela Santoni
Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process...
2016: Frontiers in Immunology
Rachel M Kratofil, Paul Kubes, Justin F Deniset
Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Chang-Man An, Shin-Ok Jo
BACKGROUND AND OBJECTIVE: In general, adequate movement of the ankle joint is known to play an important role in functional activities. Stroke survivors frequently have limited range of motion of the ankle, leading to dysfunctional weight transfer toward the paretic lower limb during standing or gait. The purpose of this study was to investigate the effects of talocrural mobilization with movement (MWM) on ankle strength, dorsiflexion passive range of motion (DF-PROM), and weight-bearing ability on the paretic limb during standing or gait in stroke patients with limited ankle dorsiflexion...
October 17, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Félix LaRoche-Johnston, Caroline Monat, Benoit Cousineau
BACKGROUND: Group II introns are catalytically active RNA and mobile retroelements present in certain eukaryotic organelles, bacteria and archaea. These ribozymes self-splice from the pre-mRNA of interrupted genes and reinsert within target DNA sequences by retrohoming and retrotransposition. Evolutionary hypotheses place these retromobile elements at the origin of over half the human genome. Nevertheless, the evolution and dissemination of group II introns was found to be quite difficult to infer...
October 20, 2016: BMC Evolutionary Biology
Maria A Lilli, Evdokia Syranidou, Andriana Palliou, Nikolaos P Nikolaidis, George Karatzas, Nicolas Kalogerakis
A methodology was developed to assess the impact of geogenic origin hexavalent chromium uptake by carrots, and the risk of human consumption of carrots grown in Asopos River basin in Greece. A field scale experiment was conducted with carrots cultivated in treatment plots, with and without compost amendment, in order to assess the impact of carbon in the mobility and uptake of chromium by plants. The results suggested that there is a trend for chromium mobilization and uptake in the surface and the leaves of the carrots cultivated in the treatment plot with the higher carbon addition, but not in the core of the carrots...
October 17, 2016: Environmental Research
Elizabeth Lightfoot, Jennifer Blevins, Terry Lum, Amano Dube
This community-based participatory research study sought to identify the cultural health assets of the Somali and Oromo communities in one Minnesota neighborhood that could be mobilized to develop culturally appropriate health interventions. Community asset mappers conducted 76 interviews with Somali and Oromo refugees in in Minnesota regarding the cultural assets of their community. A community-university data analysis team coded data for major themes. Key cultural health assets of the Somali and Oromo refugee communities revealed in this study include religion and religious beliefs, religious and cultural practices, a strong culture of sharing, interconnectedness, the prominence of oral traditions, traditional healthy eating and healthy lifestyles, traditional foods and medicine, and a strong cultural value placed on health...
2016: Journal of Health Care for the Poor and Underserved
Paul L Schneider, Zhaoping Li
OBJECTIVE: To provide a thorough analysis of the range of ethical concerns that may present in relation to the care of the morbidly obese inpatient over the course of several years of care. METHODS: A narrative of the patient's complex medical care is given, with particular attention to the recommendations of three separate ethics committee consultations that were sought by his health care providers. An ethical analysis of the relevant issues is given within the Principles of Biomedical Ethics framework, highlighting the principles of autonomy, beneficence, non-maleficence, and justice...
2016: Narrative Inquiry in Bioethics
Ümit Aygün, Yalkçn Çalçk, Barçş Alkan, Cengiz Işçk
In this study, we present the case of a 42-year-old man with a fracture and dislocation of the left talus neck, and a fracture of the right talus neck due to a fall. This kind of fracture can be considered rare, and thus few cases have been reported. Fracture fixation was provided through cannulated screws on either side. Splints were removed after 6 weeks, and passive/active joint movement exercises were started. The patient was able to walk with partial weightbearing at 2 months and with full weightbearing at 3 months...
September 2, 2016: Journal of the American Podiatric Medical Association
Timothy D Girard, Waleed Alhazzani, John P Kress, Daniel R Ouellette, Gregory A Schmidt, Jonathon D Truwit, Suzanne M Burns, Scott K Epstein, Andres Esteban, Eddy Fan, Miquel Ferrer, Gilles L Fraser, Michelle Gong, Catherine Hough, Sangeeta Mehta, Rahul Nanchal, Sheena Patel, Amy J Pawlik, Curtis N Sessler, Thomas Strøm, William Schweickert, Kevin C Wilson, Peter E Morris
BACKGROUND: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST), provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults. METHODS: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation...
October 20, 2016: American Journal of Respiratory and Critical Care Medicine
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