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PD Access

Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
Alessandra Casnati, Raimondo Maggi, Giovanni Maestri, Nicola Della Ca', Elena Motti
A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity...
July 20, 2017: Journal of Organic Chemistry
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
Beryl X Li, Diane N Le, Kyle A Mack, Andrew McClory, Ngiap-Kie Lim, Theresa Cravillion, Scott Savage, Chong Han, David B Collum, Haiming Zhang, Francis Gosselin
A highly stereocontrolled synthesis of tetrasubstituted acyclic all-carbon olefins has been developed via a stereoselective enolization and tosylate formation, followed by a palladium-catalyzed Suzuki‒Miyaura cross-coupling of the tosylates and pinacol boronic esters in the presence of Pd(OAc)2/RuPhos catalytic system. Both the enol tosylation and Suzuki‒Miyaura coupling reactions tolerate an array of electronically and sterically diverse substituents and generate high yield and stereoselectivity of the olefin products...
July 17, 2017: Journal of the American Chemical Society
Alois Fürstner, Nikolas Huwyler, Karin Radkowski, Stephan M Rummelt
An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh3)4. Under these conditions, the reaction proved robust, high yielding and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives...
July 17, 2017: Chemistry: a European Journal
Joseph F Baker, Shearwood McClelland, Breton G Line, Justin S Smith, Robert A Hart, Christopher P Ames, Chris Shaffrey, Shay Bess
BACKGROUND: Previous reports suggest that patients with Parkinson's disease (PD) have increased complication rates following spine surgery however data from these reports are limited by small patient size. The aim of this study was to utilize the National Inpatient Sample (NIS) database to compare in-hospital complications for PD compared to patients without following elective lumbar spine surgery. METHODS: The NIS database was accessed to find patients who underwent lumbar spine surgery with and without a diagnosis of PD...
July 12, 2017: World Neurosurgery
Yuganthini Vijayanathan, Fei Tieng Lim, Siong Meng Lim, Chiau Ming Long, Maw Pin Tan, Abu Bakar Abdul Majeed, Kalavathy Ramasamy
Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6...
July 13, 2017: Neurotoxicity Research
Kostas M Tsiouris, Dimitrios Gatsios, George Rigas, Dragana Miljkovic, Barbara Koroušić Seljak, Marko Bohanec, Maria T Arredondo, Angelo Antonini, Spyros Konitsiotis, Dimitrios D Koutsouris, Dimitrios I Fotiadis
PD_Manager is a mobile health platform designed to cover most of the aspects regarding the management of Parkinson's disease (PD) in a holistic approach. Patients are unobtrusively monitored using commercial wrist and insole sensors paired with a smartphone, to automatically estimate the severity of most of the PD motor symptoms. Besides motor symptoms monitoring, the patient's mobile application also provides various non-motor self-evaluation tests for assessing cognition, mood and nutrition to motivate them in becoming more active in managing their disease...
June 2017: Healthcare Technology Letters
Roberto Pecoits-Filho, Silvia Carreira Ribeiro, Adam Kirk, Helder Sebastião da Silva, Arthur Pille, Ricardo Sprenger Falavinha, Sandro Scolari Filho, Ana Elizabeth Figueiredo, Pasqual Barretti, Thyago Proença de Moraes
The prevalence of patients on automated peritoneal dialysis (APD) is increasing worldwide and may be guided by clinical characteristics, financial issues and patient option. Whether socioeconomic factors at the patient level may influence the decision for the initial peritoneal dialysis (PD) modality is unknown. This is a prospective cohort study. The primary outcome of interest was the probability to start PD on APD. The inclusion criteria were adult patients incident in PD. Exclusion criteria were missing data for either race or initial PD modality...
July 12, 2017: Scientific Reports
Rasmus Røge, Mogens Vyberg, Søren Nielsen
Treatment using immunotherapy against PD-L1 or PD-1 has become one of the hottest topics in Pathology and Oncology. Correct selection of patients eligible for treatment requires optimal immunohistochemical staining protocols. Treatment with pembrolizumab requires diagnostic examination of the patient's tumour using the companion diagnostic Ready-To-Use pharmDx kit from Dako Agilent based on the mAb 22C3 clone on the Autostainer platform. However, not all diagnostic pathology labs have access to this staining platform...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
Yang-Yang Xing, Jian-Biao Liu, Chuan-Zhi Sun, Fang Huang, De-Zhan Chen
The Pd(ii)-catalyzed site-selective δ-C(sp(3))-H alkenylation in the presence of more accessible γ-C(sp(3))-H bonds is investigated by DFT calculations. Migratory insertion is found to be both the rate-limiting and the selectivity-determining step. The origin of the unusual site-selectivity is originally attributed to the different steric repulsion between the alkyne and palladacycle; however, our theoretical results reveal that the inherent electronic effect instead of steric repulsion determines the site-selectivity...
July 11, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Kyounghoon Lee, Courtney M Donahue, Scott R Daly
The synthesis, coordination chemistry, and reactivity of two diphosphines containing the cyclic triaminoborane 1,8,10,9-triazaboradecalin (TBD) are described. To evaluate the ligand-centered reactivity of (Ph)TBDPhos and (iPr)TBDPhos, the complexes ((Ph)TBDPhos)MCl2 and ((iPr)TBDPhos)MCl2, where M = Ni and Pd, were prepared and characterized by elemental analysis, multinuclear NMR spectroscopy ((1)H, (13)C, (31)P, and (11)B), and single-crystal X-ray diffraction (XRD). Despite very low boron Lewis acidity in the TBD backbone, ((Ph)TBDPhos)NiCl2 (1) and ((Ph)TBDPhos)PdCl2 (3) react with H2O, alcohols, and hydrated fluoride reagents in the presence of NEt3 to yield trans H-O or H-F addition across the bridgehead N-B bond...
July 11, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Joseph P A Harrity, Benjamin Allen, Christopher Lakeland
Pd catalysis offers access to a range of dipolar intermediates that permit significant opportunities for the synthesis of functionalized heterocycles. The combination of electrophilic π-allyl Pd fragments and C-, N- and O-centered nucleophiles allows these intermediates to react with simple substrates to furnish a range of high value products with control of chemo-, regio- and stereo-selectivity.
July 7, 2017: Chemistry: a European Journal
Helena S Buchanan, Steven M Pauff, Tilemachos D Kosmidis, Andrea Taladriz-Sender, Olivia I Rutherford, Marine Z C Hatit, Sabine Fenner, Allan J B Watson, Glenn A Burley
Two Pd-catalyzed methods to access 6-heteroaryl 2-aminopurine ribonucleosides from 6-chloroguanosine are described. First, Pd-132-catalyzed Suzuki-Miyaura cross-coupling using a series of boron substrates and 6-chloroguanosine forms 6-heteroaryl-2-aminopurines in a single step. The versatility of 6-chloroguanosine is further demonstrated using a modified Sonogashira coupling employing potassium iodide as an additive. Finally, the utility of the 6-alkynyl-2-aminopurine ribonucleoside as a dipolarophile in [3 + 2] cycloadditions is presented, affording triazoles and isoxazoles when reacted with azide and isonitrile 1,3-dipoles, respectively...
July 6, 2017: Organic Letters
Sylwester Domański, Olga Staszewska-Krajewska, Wojciech Chaładaj
A four-component Pd-catalyzed protocol for direct synthesis of perfluoroalkyl-substituted enones is reported. Under mild conditions and low catalyst loading, alkynes, iodoperfluoroalkanes, (hetero)arylboronic acids, and carbon monoxide are assembled into highly-elaborated products with good yields and excellent regio- and stereoselectivities. The configuration of the products was confirmed by the observation of a through-space 13C-19F couplings, accessible through the analysis of routine 13C NMR spectra.
July 5, 2017: Journal of Organic Chemistry
Vesna D Stojanović, Svetlana S Bukarica, Jelena B Antić, Aleksandra D Doronjski
BACKGROUND: The aim of this retrospective study is to evaluate clinical characteristics and outcomes of very low birth weight (VLBW) neonates with acute kidney injury (AKI) treated with peritoneal dialysis (PD). METHODS: This retrospective study included 10 VLBW neonates treated with PD. Intravenous (IV) cannula and umbilical venous catheter were used for the peritoneal access. RESULTS: Mean age at the moment of starting PD was 14.9 ± 9.3 days...
July 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Janice B Lin, Tejas K Shah, Adam E Goetz, Neil K Garg, K N Houk
We report the design and synthesis of a new class of indole-based conjugated trimers. The targeted compounds are accessed from in situ generated, highly reactive indolyne intermediates using Pd-catalyzed cyclotrimerization reactions. By harnessing three indolyne isomers, six isomeric indole trimers are accessible, none of which have been previously synthesized. Using computational analysis, we describe the structural and photophysical properties of these unique compounds. This study showcases the use of indolynes in transition metal-catalyzed reactions, while providing access to a new class of conjugated trimers, including highly bent heteroaromatic compounds...
July 18, 2017: Journal of the American Chemical Society
Hans-Jörg Himmel, David Fridolin Schrempp, Elisabeth Kaifer, Hubert Wadepohl, Elisa Schneider
A new redox-active 4,5-bisguanidino-substituted o-benzoquinone ligand L is synthesized, that allows a rational access to heterobinuclear complexes by the sequential coordination of two metals. In the examples discussed in this work, mononuclear Cu and Pd complexes are prepared in a first coordination step, and these complexes are then used as precursors to homobinuclear [Cu(II)-L(0)-Cu(II)] and heterobinuclear [Pd(II)-L(0)-Cu(II)] complexes. In the heterobinuclear complex, the Pd(II) is coordinated by the softer bisguanidine side of L and the Cu(II) by the harder dioxolene side (in line with the HSAB concept)...
June 27, 2017: Chemistry: a European Journal
Xiaobing Xu, Jianchao Liu, Lin Lu, Furong Wang, Biaolin Yin
We report regioselective intramolecular direct C-3 and C-2 arylations of the indole rings of N-(o-bromophenyl)-3-indolecarboxamides for diastereospecific production of spiro-indoline-3,3'-oxindoles and 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones, respectively, under different reaction conditions and possibly involving two different pathways.
July 6, 2017: Chemical Communications: Chem Comm
Jacqueline Jiménez, Byeong-Seon Kim, Patrick J Walsh
Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of the isoindolinones with aryl bromides (22 examples) using a Pd(OAc)2/NIXANTPHOS-based catalyst system. Additionally 3-aryl 3-hydroxy isoindolinone derivatives, which exhibit anti-tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3-hydroxyl group. Furthermore, a tandem arylation/allylic substitution reaction is advanced in which both the arylation and allylic substitution are catalyzed by the same palladium catalyst...
September 1, 2016: Advanced Synthesis & Catalysis
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