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https://www.readbyqxmd.com/read/29454094/synergistic-activity-of-bet-inhibitor-bi-894999-with-plk-inhibitor-volasertib-in-aml-in-vitro-and-in-vivo
#1
Ulrike Tontsch-Grunt, Dorothea Rudolph, Irene Waizenegger, Anke Baum, Daniel Gerlach, Harald Engelhardt, Melanie Wurm, Fabio Savarese, Norbert Schweifer, Norbert Kraut
Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment...
February 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29453816/lewis-acid-catalyzed-stereoselective-dearomative-coupling-of-indolylboron-ate-complexes-with-d-a-cyclopropanes-and-alkyl-halides
#2
Saikat Das, Constantin Gabriel Daniliuc, Armido Studer
Indolylboron ate complexes readily generated from 2-lithio indoles and boronic esters undergo multicomponent dearomative coupling with D-A cyclopropanes and alkyl halides in the presence of Sc(OTf)3 as a catalyst. Reactions proceed with complete diastereoselectivity and excellent stereospecificity to provide indolines bearing three contiguous stereocenters. The valuable boronic ester moiety remains in the product and allows for subsequent functionalization.
February 17, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29453732/the-influence-of-postgraduate-qualifications-on-educational-identity-formation-of-healthcare-professionals
#3
Ahsan Sethi, Susie Schofield, Sean McAleer, Rola Ajjawi
Demand for postgraduate qualifications in medical education can be judged by the increase in providers worldwide over the last two decades. However, research into the impact of such courses on identity formation of healthcare professionals is limited. This study investigates the influence of such programmes on graduates' educational identities, practices and career progression. Informed by constructivist grounded theory (CGT), semi-structured interviews were conducted with 27 graduates (2008-2012) from one postgraduate programme, who were at different stages in their careers worldwide...
February 16, 2018: Advances in Health Sciences Education: Theory and Practice
https://www.readbyqxmd.com/read/29453715/the-influence-of-heavy-metals-polyaromatic-hydrocarbons-and-polychlorinated-biphenyls-pollution-on-the-development-of-antibiotic-resistance-in-soils
#4
Andrey Vladimirovich Gorovtsov, Ivan Sergeevich Sazykin, Marina Alexandrovna Sazykina
The minireview is devoted to the analysis of the influence of soil pollution with heavy metals, polyaromatic hydrocarbons (PAHs), and the polychlorinated biphenyls (PCBs) on the distribution of antibiotics resistance genes (ARGs) in soil microbiomes. It is shown that the best understanding of ARGs distribution process requires studying the influence of pollutants on this process in natural microbiocenoses. Heavy metals promote co-selection of genes determining resistance to them together with ARGs in the same mobile elements of a bacterial genome, but the majority of studies focus on agricultural soils enriched with ARGs originating from manure...
February 16, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29453648/supplemental-diagnosis-of-gyrodactylus-fairporti-van-cleave-1921-monogenea-from-1-month-old-black-bullhead-ameiurus-melas-in-riverside-pools-in-wisconsin
#5
Eric Leis, Russell Easy, David Cone
Samples of Gyrodactylus fairporti Van Cleave, 1921 from young-of-the-year black bullhead (Ameiurus melas) stranded in riverside pools of the Black River (La Crosse County,) WI, USA, are used to supplement the species diagnosis, including new details on the marginal hook sickles, the male copulatory organ (MCO), and 18S rRNA gene sequence data. The anchors of G. fairporti are relatively long and thin, 58.2 ± 1.2 μm in length; roots 15.5 ± 1.0 μm; shaft 38.1 ± 1.5 μm; point 31.3 ± 1.5 μm. The ventral bar is 19...
February 17, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29453523/digital-versus-light-microscopy-assessment-of-surgical-margin-status-after-radical-prostatectomy
#6
Metka Volavšek, Ana Blanca, Rodolfo Montironi, Liang Cheng, Maria R Raspollini, Nuno Vau, Jorge Fonseca, Francesco Pierconti, Antonio Lopez-Beltran
Positive surgical margin (PSM) extension reported as focal or non-focal/extensive is an important pathologic prognostic parameter after radical prostatectomy. Likewise, there is limited or no agreement on how to measure and what the best cut-off points to be used in practice are. We hypothesized that digital microscopy (DM) would potentially provide a more objective way to measure PSM and better define its clinical significance. To further our knowledge, we have evaluated PSM status in 107 laparoscopic radical prostatectomies using digital and conventional light microscopy (LM)...
February 16, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29453506/illness-beliefs-treatment-beliefs-and-information-needs-as-starting-points-for-patient-information-the-evaluation-of-an-intervention-for-patients-with-depression
#7
Manuela Glattacker, Katja Heyduck, Cornelia Meffert, Teresa Jakob
Patients with depression are often dissatisfied with disease- and therapy-related information. The objective of this study was to evaluate an intervention that applied the Common Sense Model to the provision of information during inpatient rehabilitation for patients with depression. The intervention was evaluated in a sequential control group design. Analyses of covariance were used to assess differences between the control and intervention groups. Changes with respect to illness and treatment beliefs (personal control, treatment control, coherence and concerns about medicines), satisfaction with information about medicines, illness and rehabilitation, and depressive burden were selected as primary outcome measures...
February 16, 2018: Journal of Clinical Psychology in Medical Settings
https://www.readbyqxmd.com/read/29453480/limited-open-reduction-and-percutaneous-plate-osteosynthesis-alternative-option-to-minimally-invasive-plate-osteosynthesis-in-management-of-distal-tibia-fractures
#8
Shambhu Sah, Bikash Kc, Sailoj Jung Dangi, Rem Kumar Rai, Roshan Yadav
INTRODUCTION: The management of distal tibia fracture is challenging because of the limited soft tissue coverage and poor vascularity around the bone in that area. Minimally invasive percutaneous plate osteosynthesis is a novel technique in this regard but needs fluoroscopy. In unavailability of fluoroscopy or its technical malfunction, limited open reduction percutaneous plate osteosynthesis becomes useful. The aim of this study is to compare the outcomes of distal tibia fractures treated by LORPPO and MIPPO techniques in terms of duration of hospital stay, full weight bearing, union time and complications...
October 2017: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#9
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453086/pegylated-polyaminoacid-capped-mesoporous-silica-nanoparticles-for-mitochondria-targeted-delivery-of-celastrol-in-solid-tumors
#10
Ju Yeon Choi, Biki Gupta, Thiruganesh Ramasamy, Jee-Heon Jeong, Sung Giu Jin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
The major goal of cancer chemotherapy is to maximize the therapeutic efficacy of anticancer drugs, while minimizing their associated side effects. Celastrol (CST), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has been reported to exhibit significant anticancer effects in various in vitro and in vivo cancer models. Nanoparticulate drug delivery systems could be employed to preserve and enhance the pharmacological effects of CST in cancer cells. Among these, mesoporous silica nanoparticles (MSNs) are one of the most promising drug delivery systems...
February 11, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29453053/ultrasound-molecular-imaging-of-acute-cardiac-transplantation-rejection-using-nanobubbles-targeted-to-t-lymphocytes
#11
Jinfeng Liu, Yihan Chen, Guohua Wang, Qing Lv, Yali Yang, Jing Wang, Pingyu Zhang, Jie Liu, Yu Xie, Li Zhang, Mingxing Xie
Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB CD3 ) or isotype antibody (NB con ) were prepared and characterized...
February 8, 2018: Biomaterials
https://www.readbyqxmd.com/read/29453018/-management-of-rhinosinusitis-in-primary-care
#12
N Gómez Gabaldón, C Manzanares Arnaiz, L Noguero Cánovas, J Juan Armas
Acute rhinosinusitis is an important health problem. Even though its frequency is not well documented in our country?, the economic burden it bears is not insignificant as it notably alters the quality of life of affected patients. Its diagnosis is generally clinical in nature, with further studies reserved only for the differential diagnoses of complications or tumour-like processes. The most frequent causes are viral infections, although Streptococcus pneumoniae and Haemophilus influenzae are the most commonly isolated bacterial agents...
February 13, 2018: Semergen
https://www.readbyqxmd.com/read/29452973/the-alpha-defensin-test-for-diagnosing-periprosthetic-joint-infection-in-the-setting-of-an-adverse-local-tissue-reaction-secondary-to-a-failed-metal-on-metal-bearing-or-corrosion-at-the-head-neck-junction
#13
Kamil T Okroj, Tyler E Calkins, Erdan Kayupov, Michael M Kheir, Joshua S Bingham, Christopher P Beauchamp, Javad Parvizi, Craig J Della Valle
BACKGROUND: In patients with adverse local tissue reaction (ALTR) secondary to a failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI. The purpose of this multicenter, retrospective study was to evaluate the accuracy of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR. METHODS: We reviewed medical records of 26 patients from 3 centers with ALTR that had an alpha-defensin test performed...
January 16, 2018: Journal of Arthroplasty
https://www.readbyqxmd.com/read/29452945/reduction-sensitive-fluorescence-enhanced-polymeric-prodrug-nanoparticles-for-combinational-photothermal-chemotherapy
#14
Yuanyuan Zhang, Dan Yang, Hongzhong Chen, Wei Qi Lim, Fiona Soo Zeng Phua, Guanghui An, Piaoping Yang, Yanli Zhao
In this study, a reduction-sensitive supramolecular polymeric drug delivery system was developed for combinational photothermal-chemotherapy of cancer. The multifunctional system was self-assembled by specific host-guest interactions between hydrophilic β-cyclodextrin functionalized hyaluronic acid and adamantane linked camptothecin/dye conjugate, where a near-infrared (NIR) absorbing dye IR825 was loaded. The hydrophilic hyaluronic acid shell endows the assembly with excellent colloidal stability and biocompatibility...
February 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452833/endothelial-vascular-cell-adhesion-molecule-1-is-a-marker-for-high-risk-carotid-plaques-and-target-for-ultrasound-molecular-imaging
#15
Craig C Weinkauf, Kirsten Concha-Moore, Jonathan R Lindner, Edmund R Marinelli, Kyle P Hadinger, Sandipan Bhattacharjee, Scott S Berman, Kay Goshima, Luis R Leon, Terry O Matsunaga, Evan Unger
BACKGROUND: Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. METHODS: Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients...
February 13, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29452419/temozolomide-associated-hypermutation-in-gliomas
#16
Serah Choi, Yao Yu, Matthew R Grimmer, Michael Wahl, Susan M Chang, Joseph F Costello
Low-grade gliomas cause considerable morbidity and most will recur after initial therapy. At recurrence, low-grade gliomas can undergo transformation to high-grade gliomas (grade III or grade IV), which are associated with worse prognosis. Temozolomide (TMZ) provides survival benefit in patients with glioblastomas (GBMs) but its value in patients with low-grade gliomas is less clear. A subset of TMZ-treated, IDH-mutant, low-grade astrocytomas recur as more malignant tumors with thousands of de novo, coding mutations bearing a signature of TMZ-induced hypermutation...
February 14, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29452304/the-chondrocyte-channelome-a-narrative-review
#17
Ali Mobasheri, Csaba Matta, Ilona Uzielienè, Emma Budd, Pablo Martín-Vasallo, Eiva Bernotiene
Chondrocytes are the main cells in the extracellular matrix of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function...
February 13, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29451939/reverse-shoulder-arthroplasty-in-the-weight-bearing-versus-non-weight-bearing-shoulder-mid-term-outcomes-with-minimum-5-year-follow-up
#18
Derek J Cuff, Brandon G Santoni
This retrospective review evaluated the mid-term outcomes of cemented reverse shoulder arthroplasty in patients who use the shoulder for weight bearing (WB) vs non-weight-bearing (NWB) patients. Twenty-five shoulders of 21 patients who used their upper extremity for WB (WB group) were treated with cemented reverse shoulder arthroplasty and followed for a minimum of 5 years postoperatively (average, 73 months). Seventy-five consecutive shoulders of 72 patients who were NWB (NWB group) were treated and matched for duration of follow-up (average, 72 months) to serve as a control group...
February 16, 2018: Orthopedics
https://www.readbyqxmd.com/read/29451783/sufex-click-chemistry-enabled-late-stage-drug-functionalization
#19
Zilei Liu, Jie Li, Suhua Li, Gencheng Li, K Barry Sharpless, Peng Wu
Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the S VI -F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products...
February 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29451774/organic-semiconducting-photoacoustic-nanodroplets-for-laser-activatable-ultrasound-imaging-and-combinational-cancer-therapy
#20
Wei Tang, Zhen Yang, Sheng Wang, Zhantong Wang, Jibin Song, Guocan Yu, Wenpei Fan, Yunlu Dai, Jingjing Wang, Lingling Shan, Gang Niu, Quli Fan, Xiaoyuan Chen
Combination of photoacoustic (PA) and ultrasound (US) imaging offers high spatial resolution images with deep tissue penetration, which shows great potentials in applications in medical imaging. Development of PA/US dual-contrast agents with high contrast and excellent biocompatible is of great interest. Herein, an organic semiconducting photoacoustic nanodroplet, PS-PDI-PAnD, is developed by stabilizing low-boiling-point perfluorocarbon (PFC) droplet with a photoabsorber and photoacoustic agent of perylene diimide (PDI) molecules and co-encapsulating the droplet with photosensitizers of ZnF16Pc molecules...
February 16, 2018: ACS Nano
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