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Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Emily S Walker, Seung Ryul Na, Daehwan Jung, Stephen D March, Joon-Seok Kim, Tanuj Trivedi, Wei Li, Li Tao, Minjoo L Lee, Kenneth M Liechti, Deji Akinwande, Seth R Bank
We report the first direct dry transfer of a single-crystalline thin film grown by molecular beam epitaxy. A double cantilever beam fracture technique was used to transfer epitaxial bismuth thin films grown on silicon (111) to silicon strips coated with epoxy. The transferred bismuth films retained electrical, optical, and structural properties comparable to the as-grown epitaxial films. Additionally, we isolated the bismuth thin films on freestanding flexible cured-epoxy post-transfer. The adhesion energy at the bismuth/silicon interface was measured to be ∼1 J/m(2), comparable to that of exfoliated and wet transferred graphene...
October 24, 2016: Nano Letters
Fabrizio Bernini, Daniele Malferrari, Marcello Pignataro, Carlo Augusto Bortolotti, Giulia Di Rocco, Lidia Lancellotti, Maria Franca Brigatti, Rakez Kayed, Marco Borsari, Federica Del Monte, Elena Castellini
The pathological hallmark of misfolded protein diseases and aging is the accumulation of proteotoxic aggregates. However, the mechanisms of proteotoxicity and the dynamic changes in fiber formation and dissemination remain unclear, preventing a cure. Here we adopted a reductionist approach and used atomic force microscopy to define the temporal and spatial changes of amyloid aggregates, their modes of dissemination and the biochemical changes that may influence their growth. We show that pre-amyloid oligomers (PAO) mature to form linear and circular protofibrils, and amyloid fibers, and those can break reforming PAO that can migrate invading neighbor structures...
October 24, 2016: Scientific Reports
María Luján Cuestas
Since the British scientist Michael Houghton along with George Kuo, Qui-Lim Choo (Chiron Corporation Emeryville), and Daniel W. Bradley (Centers for Disease Control and Prevention) co-discovered the causative agent of hepatitis C in 1989, so much progress has been made for the screening of blood donors and management of this chronic liver disease. In this regard, direct-acting antiviral agents (DAAs) have emerged as the potential "cure" of this slowly progressing and devastating disease. However, improvements are still clearly required since the anti-hepatitis C drugs currently available in the market are so extremely expensive (i...
October 19, 2016: Mini Reviews in Medicinal Chemistry
Prithviraj Bose, Srdan Verstovsek
INTRODUCTION: Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. AREAS COVERED: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
October 22, 2016: Expert Opinion on Pharmacotherapy
M Amélia Santos, Karam Chand, Sílvia Chaves
Alzheimer's disease (AD) is a serious progressive neurological disorder, characterized by impaired cognition and profound irreversible memory loss. The multifactorial nature of AD and the absence of a cure so far have stimulated medicinal chemists worldwide to follow multitarget drug-design strategies based on repositioning approved drugs. This review describes a summary of recently published works focused on tailoring new derivatives of US FDA-approved acetylcholinesterase inhibitors, in addition to huperzine (a drug approved in China), either by hybridization with other pharmacophore elements (to hit more AD targets), or by combination of two FDA-approved drugs...
October 24, 2016: Future Medicinal Chemistry
Adewumi Adediran, Modu Baba Kagu, Tamunomieibi Wakama, Aliyu Ahmadu Babadoko, Dapus Obadiah Damulak, Sunday Ocheni, Marcus Inyama Asuquo
Background. Sickle cell anaemia (SCA) is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution's research and ethics committee...
2016: Bone Marrow Research
Yang Yu, Yu-Feng Zhou, Xiao Li, Mei-Ren Chen, Gui-Lin Qiao, Jian Sun, Xiao-Ping Liao, Ya-Hong Liu
This work aimed to characterize the mammary gland pharmacokinetics of cefquinome after an intramammary administration and integrate pharmacokinetic/pharmacodynamic model. The pharmacokinetic profiles of cefquinome in gland tissue were measured using high performance liquid chromatograph. Therapeutic regimens covered various dosages ranging from 25 to 800 μg/gland and multiple dosing intervals of 8, 12, and 24 h. The in vivo bacterial killing activity elevated when dosage increased or when dosing intervals were shortened...
2016: Frontiers in Microbiology
Renato Cassio Roperto, Thiago Soares Porto, Lisa Lang, Sorin Teich, Sean Weber, Omar El-Mowafy, Sizenando Toledo Porto-Neto
During a fiber post cementation, bonding failure often occurs at the junction between the fiber-post and resin-cement. Because this failure requires better characterization, we evaluated if different post surface treatment can affect the bond strength of urethane dimethacrylate (UDMA) fiber-posts with resin-cements. Three groups were created: G1: no treatment/silane; G2: ethyl alcohol (96° GL)/silane; G3: 24% H2O2/silane and further divided into four subgroups: I-Unicem/3MESPE; II-BisCem/Bisco; III-Panavia SA/Kuraray and IV-DuoLink/Bisco...
October 22, 2016: Dental Materials Journal
Le Zhang, Yunshan Zhao, Zhipeng A Wang, Kunhua Wei, Bin Qiu, Chunhong Zhang, QiYan Wang-Müller, Minhui Li
ETHNOPHARMACOLOGICAL RELEVANCE: As a group of important medicine plants, Boschniakia rossica (Cham. et Schltdl) Fedtsch. and B. himalaica Thoms, which are the only two species in the genus Boschniakia (Orobanchaceae), have long been used in traditional Chinese medicine for their multiple therapeutic uses related to enhanced renal function, erectile dysfunction, defaecate and hepatoprotective. Additionally, the two species are also used as dietary supplements in wine, cosmetics, and other healthy food...
October 20, 2016: Journal of Ethnopharmacology
Isil Cekic-Nagas, Gulfem Ergun, Ferhan Egilmez, Pekka Kalevi Vallittu, Lippo Veli Juhana Lassila
PURPOSE: The aim of this study was to evaluate the effects of hydrofluoric acid treatment on bond strength of resin cements to three different types of ceramic/glass containing CAD-CAM block composite materials. METHODS: CAD-CAM block materials of polymer infiltrated (Vita Enamic), resin nanoceramic (Lava Ultimate) and nanoceramic (Cerasmart) with a thickness of 1.5mm were randomly divided into two groups according to the surface treatment performed. In Group 1, specimens were wet-ground with silicon carbide abrasive papers up to no...
March 10, 2016: Journal of Prosthodontic Research
Hilary J Goldberg
No abstract text is available yet for this article.
September 13, 2016: Journal of Heart and Lung Transplantation
Mitiku Bajiro, Daniel Dana, Mio Ayana, Daniel Emana, Zeleke Mekonnen, Belay Zawdie, Asfaw Garbi, Ashenafi Kure, Ahmed Zeynudin
BACKGROUND: Intestinal schistosomiasis is one of the neglected tropical parasitic diseases caused by Schistosoma mansoni. Currently, the control measures for the disease are mainly based on mass drug administration (MDA) with praziquantel (PZQ) targeting the school-age children. In Ethiopia, the potential foci for schistosomiasis and therapeutic efficacy of PZQ among school-age children remain poorly explored. Therefore, we determined both the prevalence and intensity of S. mansoni infection and the therapeutic efficacy of PZQ among school children in the Manna District (new foci for S...
October 24, 2016: Parasites & Vectors
Qian Li, Dong-Mei Yuan, Li-Hong Ma, Chen-Hui Ma, Ya-Fang Liu, Tang-Feng Lv, Yong Song
Malignant pleural effusion (MPE) is associated with a poor prognosis in lung cancer. Currently, no effective cure exists for MPE. Chloroquine (CQ) has been demonstrated to induce vascular normalization and inhibit tumor growth. The aim of this study was to assess whether CQ affects MPE. The xenografts mice were divided into normal saline (NS), CQ, or bevacizumab (BE) group. Tumor growth and microvascular density (MVD) were monitored. We explored the effect of CQ on the proliferation, survival, and proangiogenic signaling of tumor cells in vitro...
October 22, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jan Baars
Aging and time are interconnected because aging is basically living seen in a temporal perspective. This makes 'time' an important concept in trying to explain aging. However, throughout modernity time has increasingly been identified as clock time: perfectly fit to measure 'age' as time since birth but failing to explain 'age' as an indicator of aging processes and even less adequate to grasp the lived time of human beings. Moreover, the clock as a cultural idol of instrumentalist perfection has led to approaching human aging in terms of maintenance and repair, inspiring a neglect and depreciation of human vulnerability...
October 22, 2016: Biogerontology
Ming Zhang, Ai-Juan Wang, Jun-Ming Li, Na Song, Yang Song, Rui He
Hydroxyapatite (HAp) nanoparticle stabilized Pickering emulsion was fabricated with poly(l-lactic acid) dissolved in dichloromethane (CH2Cl2) solution as oil phase and HAp aqueous dispersion as aqueous phase. Pickering emulsion was cured via in situ solvent evaporation method. Effect of PLLA concentrations, pH value, HAp concentrations, oil-water ratio, emulsification rates and times were studied on emulsion stability and emulsion type, etc. The results indicated emulsion stability increased with the increase of HAp concentration, emulsification rate and time; it is very stable when pH value of aqueous phase was adjusted to 10...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Chen-Hsiang Yeang, Robert A Beckman
BACKGROUND: Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies...
October 22, 2016: Biology Direct
Feng Yang, Wen-Xiong Li, Zhu Liu, Li Liu
BACKGROUND: Cervical spondylosis is a very common disorder and cervical spondylotic radiculopathy (CSR) is the most common form of spinal degenerative disease. Its clinical manifestations focus on pain and numbness of the neck and arm as well as restricted movement of the neck, which greatly affect the patient's life and work. The orthopedic of traditional Chinese medicine (TCM) theory holds that the basic pathologic change in spinal degenerative diseases is the imbalance between the dynamic system and the static system of the cervical spine...
October 22, 2016: Trials
Andrea Angelini, Andreas F Mavrogenis, Eugenio Rimondi, Giuseppe Rossi, Pietro Ruggieri
This review summarizes current concepts in the diagnosis and management of the patients with eosinophilic granuloma. Given the benign biology, the clinical course, and the pediatric group of patients that this condition more commonly affects, a treatment approach that carries a lower risk of complications while ensuring a successful cure is desirable. Variable treatment options have been reported with satisfactory results and a recurrence rate of less than 20 %. In this setting, symptomatic lesions that are accessible in the spine or the extremities may be treated with intralesional methylprednisolone injection after tissue biopsy for histological diagnosis...
October 21, 2016: Journal of Orthopaedics and Traumatology: Official Journal of the Italian Society of Orthopaedics and Traumatology
Ana Mladenovič, Sandra Hamler, Nina Zupančič
The environmental acceptability of geotechnical composites made of treated municipal sewage sludge (SwS) and paper ash (PA) after two different curing periods has been investigated. The mineral composition of such composites, including their content of major oxides, is mainly influenced by the PA. The content of potentially toxic elements (PTEs) in the initial materials and in the composites varies considerably. In the SwS the Ba, Cd, Cr, Cu, Hg, Ni and Zn contents are above the legally permitted limits. The PTE content of PA are lower, but still somewhat above the permitted values for Ba and Cu...
October 21, 2016: Environmental Science and Pollution Research International
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