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Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWAS) in four European-ancestry cohorts, six SNPs in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta=0...
March 14, 2018: Human Molecular Genetics
Mario Alberto Flores-Valdez, Cristian Alfredo Segura-Cerda, Jorge Gaona-Bernal
Effective prevention of tuberculosis (Tb) would undoubtedly be of paramount relevance in the control of its global burden, which resulted in more than 6 million new cases in 2016. Research aimed to improve the current vaccine, Bacillus Calmette- Guérin (BCG), or directed to develop new candidates, has taken into account the interaction between the host and Mycobacterium tuberculosis (Mtb). Recently, autophagy, an intracellular process of the host, has been shown to act as a mechanism that contributes to bacilli clearance in vitro and in vivo...
March 13, 2018: Molecular Immunology
Nicola L D Overton, Axel A Brakhage, Andreas Thywißen, David W Denning, Paul Bowyer
Allergic bronchopulmonary aspergillosis (ABPA) in asthma is a severe, life-affecting disease that potentially affects over 4.8 million people globally. In the UK, ABPA is predominantly caused by the fungus Aspergillus fumigatus. Phagocytosis is important in clearance of this fungus, and Early Endosome Antigen 1 (EEA1) has been demonstrated to be involved in phagocytosis of fungi. We sought to investigate the role of EEA1 mutations and phagocytosis in ABPA. We used exome sequencing to identify variants in EEA1 associated with ABPA...
2018: PloS One
Sherine Ismail, Mohamed Osman, Rayf Abulezz, Hani Alhamdan, K H Mujtaba Quadri
Pharmacists possess pivotal competencies and expertise in developing clinical pathways (CPs). We present a tertiary care facility experience of pharmacists vis-a-vis interprofessional collaboration for designing and implementing CPs. We participated in the development of CPs as leading members of a collaborative team of healthcare professionals. We reviewed literature, aligning it with hospital formulary and institutional standards, and participated in weekly team meetings for six months. Several tools and services were adapted to guide prescribing and standardization of care through time-bound order sets...
March 16, 2018: Pharmacy (Basel, Switzerland)
Enrico Gugliandolo, Roberta Fusco, Giovanna Ginestra, Ramona D'amico, Carlo Bisignano, Giuseppina Mandalari, Salvatore Cuzzocrea, Rosanna Di Paola
BACKGROUND: Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. PA LPS is recognized by toll like receptors 4 (TLR4) and has been shown to induce lung inflammation in vivo. In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage...
March 15, 2018: Shock
Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Oscar H L Bing
Ammonia plays a central role in the life and death of all living organisms and has been studied for over one hundred years. Ammonia is necessary for growth and development but it is toxic in excess and, as a result, differing methods of ammonia neutralization have evolved. Following physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is FDA approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia clearance...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Charles S Dela Cruz, Richard G Wunderink, David C Christiani, Stephania A Cormier, Kristina Crothers, Claire M Doerschuk, Scott E Evans, Daniel R Goldstein, Purvesh Khatri, Lester Kobzik, Jay K Kolls, Bruce D Levy, Mark L Metersky, Michael S Niederman, Roomi Nusrat, Carlos J Orihuela, Paula Peyrani, Alice S Prince, Julio A Ramírez, Karen M Ridge, Sanjay Sethi, Benjamin T Suratt, Jacob I Sznajder, Ephraim L Tsalik, Allan J Walkey, Sachin Yende, Neil R Aggarwal, Elisabet V Caler, Joseph P Mizgerd
Pneumonia is a complex pulmonary disease in need of new clinical approaches. While triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as ARDS and to organ dysfunction beyond the lungs and overextended time-frames after pathogen clearance, some of which increase the risk for subsequent pneumonias...
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
Igor Filipčić, Ivona Šimunović Filipčić, Tomislav Gajšak, Željko Milovac, Strahimir Sučić, Ena Ivezić, Sandra Zečević Penić, Ivana Orgulan, Damir Šebo, Vjekoslav Jeleč, Žarko Bajić
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be effective in the treatment of major depressive disorder (MDD). At present, no randomized controlled trials (RCT) have compared the efficacy and safety of rTMS delivered by the figure-8-coil and the H1-coil. We describe an industry-independent, randomized, controlled, single-blinded, single-center study protocol assessing the differences in efficacy and safety of rTMS for patients diagnosed with MDD with the H1-coil and figure-8-coil as an add-on to stable pharmacotherapy or pharmacotherapy alone...
March 2018: Psychiatria Danubina
Kusum Vats, Rohit Sharma, Haladhar Dev Sarma, Drishty Satpati, Ashutosh Dash
AIMS: The urokinase plasminogen activator receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPAR-expressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes...
March 16, 2018: Anti-cancer Agents in Medicinal Chemistry
Kristin Bjørnland, Maren Hinna, Gunnar Aksnes, Kjetil Juul Stensrud, Kjetil Ertresvåg, Anniken Bjørnstad-Østensen, Truls Sanengen, Pål-Dag Line, Ingegerd Aagenæs, Lars Aabakken, Ragnhild Emblem, Runar Almaas
OBJECTIVES: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. METHODS: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. RESULTS: Forty-five babies were identified of which 42 (93%) are alive. Forty-one patients had a Kasai portoenterostomy (PE), two had a hepaticojejunostomy and two had a primary liver transplantation...
March 16, 2018: Scandinavian Journal of Gastroenterology
Rodrigo López-Leal, Paula Diaz, Felipe A Court
Sensory neurons from dorsal root ganglion efficiently regenerate after peripheral nerve injuries. These neurons are widely used as a model system to study degenerative mechanisms of the soma and axons, as well as regenerative axonal growth in the peripheral nervous system. This chapter describes techniques associated to the study of axonal degeneration and regeneration using explant cultures of dorsal root ganglion sensory neurons in vitro in the presence or absence of Schwann cells. Schwann cells are extremely important due to their involvement in tissue clearance during axonal degeneration as well as their known pro-regenerative effect during regeneration in the peripheral nervous system...
2018: Methods in Molecular Biology
Paulo V Mezzaroba, Dalton M Pessôa Filho, Alessandro M Zagatto, Fabiana Andrade Machado
This study aimed to investigate the effect of prior LED sessions on the responses of cardiorespiratory parameters during the running incremental step test. Twenty-six healthy, physically active, young men, aged between 20 and 30 years, took part in this study. Participants performed two incremental load tests after placebo (PLA) and light-emitting diode application (LED), and had their gas exchange, heart rate (HR), blood lactate, and rating of perceived exertion (RPE) monitored during all tests. The PLA and LED conditions were compared using the dependent Student t test with significance set at 5%...
March 15, 2018: Lasers in Medical Science
Thomas Tängdén, Pier Giorgio Cojutti, Jason A Roberts, Federico Pea
BACKGROUND AND OBJECTIVES: Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations. METHODS: Therapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively...
March 15, 2018: Clinical Pharmacokinetics
Juliana Gil Melgaço, Noemi Rovaris Gardinali, Vinicius da Motta de Mello, Mariana Leal, Lia Laura Lewis-Ximenez, Marcelo Alves Pinto
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries...
2018: BioMed Research International
Maria Sunseri, Tania Ahuja, Tanya Wilcox, David Green
Unfractionated heparin and low-molecular-weight heparins are commonly used as thromboprophylaxis for hospitalized patients. Though generally considered safe at prophylactic doses, cases of catastrophic hemorrhage have been reported. The proposed mechanism involves bioaccumulation of heparin through saturation of the rapid-elimination pathway in its metabolism. We present an unusual case of an average-weight man with metastatic melanoma who suffered hemorrhage with syncope and end-organ damage while on prophylactic three times daily unfractionated heparin...
2018: Case Reports in Hematology
Delphine Lumbroso, Soaad Soboh, Avi Maimon, Sagie Schif-Zuck, Amiram Ariel, Tal Burstyn-Cohen
The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood...
2018: Frontiers in Immunology
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
Ahmet Krasniqi, Matthias D'Huyvetter, Nick Devoogdt, Fredrik Y Frejd, Jens Sorensen, Jens Sorensen, Marleen Keyaerts, Vladimir Tolmachev
Imaging of expression of therapeutic targets may enable patients' stratification for targeted treatments. The use of small radiolabeled probes based on the heavy-chain variable region of heavy-chain-only immunoglobulins or non-immunoglobulin scaffolds permits rapid localization of radiotracers in tumors and rapid clearance from normal tissues. This makes high-contrast imaging possible on the day of injection. This mini-review focuses on small proteins for radionuclide-based imaging that would allow same-day imaging, with the emphasis on clinical applications and promising preclinical developments within the field of oncology...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Alexandre Karras
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease...
March 12, 2018: Néphrologie & Thérapeutique
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