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Isabella Zhang, Silvia C Formenti, Jonathan P S Knisely
The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies...
March 15, 2018: Oncology (Williston Park, NY)
Morad Chughtai, John J Kelly, Jared M Newman, Assem A Sultan, Anton Khlopas, Nipun Sodhi, Anil Bhave, Michael C Kolczun, Michael A Mont
This study evaluated the use of telerehabilitation during the postoperative period for patients who underwent total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA). Specifically, this study evaluated the following: (1) patient compliance and adherence to the program, (2) time spent performing physical therapy exercises, (3) the usability of the virtual rehabilitation platform, and (4) clinical outcome scores in a selected primary knee arthroplasty cohort. A total of 157 consecutive patients underwent TKA ( n  = 18) or UKA ( n  = 139)...
March 16, 2018: Journal of Knee Surgery
Christopher D Witiw, Fabrice Smieliauskas, John E O'Toole, Michael G Fehlings, Richard G Fessler
BACKGROUND: Surgery for cervical radiculopathy is often approached by either anterior cervical discectomy and fusion (ACDF) or posterior cervical foraminotomy (PCF). ACDF is more common; however, recent single center studies suggest comparable efficacy and significant cost savings with PCF in appropriately selected patients. OBJECTIVE: To compare utilization, adverse events, and costs for each approach from a national perspective. METHODS: Adults undergoing single level ACDF or PCF for cervical radiculopathy were included from a US commercial health insurance claims database spanning 2003 to 2014...
March 14, 2018: Neurosurgery
Justin M Curley, Coleen Crouch, Joshua E Wilk
Introduction: Medical readiness for deployment is arguably the most important component of personnel readiness in the U.S. Army. Administrative documents called profiles provide individualized medical recommendations to the commander regarding how to best provide for a soldier's health and welfare, and contribute to an aggregated enumeration of a unit's overall readiness to deploy. Profiles that convey behavioral health (BH) limitations thus reflect what can be called the "behavioral health readiness" of the force...
March 14, 2018: Military Medicine
Michelle M Valdez, Maureen Liwanag, Charles Mount, Rechell Rodriguez, Elisea Avalos-Reyes, Andrew Smith, David Collette, Michael Starsiak, Richard Green
Introduction: Inefficiencies in the command approval process for publications and/or presentations negatively impact DoD Graduate Medical Education (GME) residency programs' ability to meet ACGME scholarly activity requirements. A preliminary review of the authored works approval process at Naval Medical Center San Diego (NMCSD) disclosed significant inefficiency, variation in process, and a low level of customer satisfaction. In order to facilitate and encourage scholarly activity at NMCSD, and meet ACGME requirements, the Executive Steering Council (ESC) chartered an interprofessional team to lead a Lean Six Sigma (LSS) Rapid Improvement Event (RIE) project...
March 14, 2018: Military Medicine
Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
Piotr Klukowski, Michal Augoff, Maciej Zieba, Maciej Drwal, Adam Gonczarek, Michal J Walczak
Motivation: Automated selection of signals in protein NMR spectra, known as peak picking, has been studied for over 20 years, nevertheless existing peak picking methods are still largely deficient. Accurate and precise automated peak picking would accelerate the structure calculation, and analysis of dynamics and interactions of macromolecules. Recent advancement in handling big data, together with an outburst of machine learning techniques, offer an opportunity to tackle the peak picking problem substantially faster than manual picking and on par with human accuracy...
March 14, 2018: Bioinformatics
Devin Ancona, Dan York, Robert J Higgins, Danika Bannasch, Peter J Dickinson
Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170 K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains...
March 14, 2018: Journal of Neuropathology and Experimental Neurology
Arjun Sethi, Valerie Voon, Hugo D Critchley, Mara Cercignani, Neil A Harrison
Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain...
March 13, 2018: Brain: a Journal of Neurology
Henry T Peng, Catherine Tenn, Oshin Vartanian, Shawn G Rhind, Jerzy Jarmasz, Homer Tien, Andrew Beckett
Introduction: Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake. Materials and Methods: We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field)...
March 14, 2018: Military Medicine
Qiaozhen Meng, Zhenling Peng, Jianyi Yang
Motivation: Coenzyme A (CoA)-protein binding plays an important role in various cellular functions and metabolic pathways. However, no computational methods can be employed for CoA-binding residues prediction. Results: We developed three methods for the prediction of CoA- and CoA derivatives-binding residues, including an ab-initio method SVMpred, a template-based method TemPred, and a consensus-based method CoABind. In SVMpred, a comprehensive set of features are designed from two complementary sequence profiles and the predicted secondary structure and solvent accessibility...
March 14, 2018: Bioinformatics
Malgorzata A Gazda, Pedro Andrade, Sandra Afonso, Jolita Dilyte, John P Archer, Ricardo J Lopes, Rui Faria, Miguel Carneiro
Racing pigeons have been selectively bred to find their way home quickly over what are often extremely long distances. This breed is of substantial commercial value and is also an excellent avian model to gain empirical insights into the evolution of traits associated with flying performance and spatial orientation. Here, we investigate the molecular basis of the superior athletic and navigational capabilities of racing pigeons using whole-genome and RNA sequencing data. We inferred multiple signatures of positive selection distributed across the genome of racing pigeons...
March 13, 2018: Molecular Biology and Evolution
Saeideh Tasharrofi, Hossein Taghdisian, Abdollah Golchoobi
In this study, pure and ternary adsorption of hydrogen sulfide (H2 S), ethylbenzene (EB), and carbon monoxide (CO) on different arrays of zigzag double wall carbon nanotube was investigated using grand canonical Monte Carlo simulations. The internal diameters of nanotube were fixed at 2r = 50.17 Å while nanotube wall distances were different values from d = 0 Å to d = 150 Å. Pure simulation results indicated that adsorption quantity of H2 S and EB in low pressure ranges of P = 1.9 bar to P = 3...
March 2, 2018: Journal of Molecular Graphics & Modelling
Laura Jayne Broome, Cristina Izura, Nuria Lorenzo-Dus
Within the literature individuals who use the internet to facilitate the sexual abuse of a minor are generally classified as being fantasy or contact driven. Classification is based upon the intended location for sexual climax: fantasy driven individuals aim to reach sexual climax online, whereas contact driven individuals target minors to achieve physical sex offline. This review systematically investigates whether there is an empirical basis for the distinction between these two proposed discrete types. Comparison of tactics and behaviour are considered to examine whether the contact vs...
March 12, 2018: Child Abuse & Neglect
Ana M Molina, Thomas E Hutson, Dmitry Nosov, Piotr Tomczak, Oleg Lipatov, Cora N Sternberg, Robert Motzer, Tim Eisen
BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover clinical study (AV-951-09-902) provided access to tivozanib for patients who progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in patients with advanced renal cell carcinoma (RCC). METHODS: Patients enrolled in this single-arm, phase 2 crossover study were previously randomised to sorafenib on TIVO-1, progressed and then crossed over to tivozanib...
March 13, 2018: European Journal of Cancer
Claudia Bello, Jianfei Bai, Bartosz K Zambron, Pilar Elías-Rodríguez, Consuelo Gajate, Inmaculada Robina, Irene Caffa, Michele Cea, Fabrizio Montecucco, Alessio Nencioni, Aimable Nahimana, Dominique Aubry, Caroline Breton, Michel A Duchosal, Faustino Mollinedo, Pierre Vogel
We have synthesized a wide array of structurally related amphiphilic compounds, containing a functionalized pyrrolidine polar group coupled to different ether-linked hydrocarbon chains, to generate novel structures with antitumor activity. These newly synthesized amphiphilic pyrrolidine-derived compounds were classified in three different sub-libraries regarding the number of hydroxyl groups substituting the pyrrolidine moiety at C3 and C4. Pyrrolidine compounds with one or none hydroxyl groups showed a potent cell killing activity against pancreatic cancer cells, but they lacked selectivity for tumor cells...
March 2, 2018: European Journal of Medicinal Chemistry
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Mousumi Pal, Utpal Nandi, Debaraj Mukherjee
Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation...
March 7, 2018: European Journal of Medicinal Chemistry
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Jana Tchekalarova, Keylla da Conceição Machado, Antonio Luiz Gomes Júnior, Ana Amélia de Carvalho Melo Cavalcante, Albena Momchilova, Rumyana Tzoneva
PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test...
March 12, 2018: Seizure: the Journal of the British Epilepsy Association
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