Immunosuppressive drugs in renal transplantation

A kidney transplant, sometimes known as a renal transplant, is the treatment of choice for kidney failure at end stage renal disease (ESRD). The renal transplant surgery is followed by a lifetime course of immunosuppressive agents, divided into initial induction phase and later maintenance phase. It is seen that the risk of acute rejection is maximum in the initial months after transplantation (induction phase) and then reduces later (maintenance phase). In induction phase there is use of high-intensity immunosuppression immediately after transplantation, when the risk of rejection is maximum and then the dose reduced for long- term therapy. The main challenge in the renal transplantation community is long- term transplant survival. Long-term graft loss is mainly due to acute and chronic graft rejection, and also due to complications of immunosuppressive therapy. Currently, there is triple therapy as conventional immunosuppressive protocol: a calcineurin inhibitor, an antimetabolite agent, and a corticosteroid. The main aim of development of new immunosuppressive agents is not only improvement of short- term outcomes but also to increase the long- term graft survival by less nephrotoxicity, and minimal side-effects

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Synthesis, characterization and in vitro antitumor activities of binary and heterobimetallic complexes of oxovanadium(IV), manganese(II), iron(II,III), cobalt(II,III), nickel(II), copper(II) & zinc(II) with <i>p</i> -hydroxy dithiobenzoate

992-997A few complexes of the types M (p &ndash;Ohdtb)2 [M=Mn(II), Cu(II) or Zn(II)], M(p -OHdtb)3 [M=Fe(Ill) or co(III)], V(p-OHdtb)4 and Ni(p-OHdtbS) (p-OHdtb = p hydroxy dithiobenzoate] and heterobimetallic complexes M[Cd(p -OHdtb)4] [M=VO2+, Mn(II), Fe(II), Co(II), Ni(II) or Zn(II) have been prepared in water ethanol medium. The complexes have been characterized by elemental analyses, magnetic susceptibility measurements, and UV-VIS, IR, ESR and NMR (1H and !3C) spectral studies. In vitro results of the binary complexes on P-815 (murine mastocytoma) indicate that the complexes show significant inhibition on 3H-thymidine and 3H-uridine incorporation in tumor cells and thus inhibit DNA and RNA replications

Total Synthesis and Determination of Absolute Configuration of Cryptorigidifoliol G

The first asymmetric total synthesis of (1S,5R,7S)-cryptorigidifoliol G and (1S,5R,7R)-cryptorigidifoliol G of the proposed natural product was achieved. The key steps in the synthesis involved Keck–Maruoka allylation, our own developed protocol for the construction of the trans-2,6-disubstituted dihydropyran, iodolactonization, cross-metathesis, Prins cyclization, and cis-Wittig olefination reaction. A comparison of the NMR as well as analytical data and thorough analysis of the 2D NMR suggested that the absolute stereochemistry of the proposed natural product is (1S,5R,7S)-cryptorigidifoliol G

Review of strategies toward the development of alloy two-dimensional (2D) transition metal dichalcogenides

Atomically thin two-dimensional (2D) transition metal dichalcogenides (TMDCs) have attracted significant attention owing to their prosperity in material research. The inimitable features of TMDCs triggered the emerging applications in diverse areas. In this review, we focus on the tailored and engineering of the crystal lattice of TMDCs that finally enhance the efficiency of the material properties. We highlight several preparation techniques and recent advancements in compositional engineering of TMDCs structure. We summarize different approaches for TMDCs such as doping and alloying with different materials, alloying with other 2D metals, and scrutinize the technological potential of these methods. Beyond that, we also highlight the recent significant advancement in preparing 2D quasicrystals and alloying the 2D TMDCs with MAX phases. Finally, we highlight the future perspectives for crystal engineering in TMDC materials for structure stability, machine learning concept marge with materials, and their emerging applications.The authors acknowledge that the study was supported as part of the Computational Materials Sciences Program funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences , under Award Number DE-SC0014607 . P.K., C.S.T. and V.K. acknowledge AOARD ( Asian Office of Aerospace Research and Development ) grant no. FA2386-19-1-4039 and Grant No. FA2386-21-1-4014 . C.S.T. acknowledges Ramanujan fellowship and core research grant of SERB, India. CST acknowledges the funding received from STARS project by MHRD, India.Scopu

The sequence of rice chromosomes 11 and 12, rich in disease resistance genes and recent gene duplications

Background: Rice is an important staple food and, with the smallest cereal genome, serves as a reference species for studies on the evolution of cereals and other grasses. Therefore, decoding its entire genome will be a prerequisite for applied and basic research on this species and all other cereals. Results: We have determined and analyzed the complete sequences of two of its chromosomes, 11 and 12, which total 55.9 Mb (14.3% of the entire genome length), based on a set of overlapping clones. A total of 5,993 non-transposable element related genes are present on these chromosomes. Among them are 289 disease resistance-like and 28 defense-response genes, a higher proportion of these categories than on any other rice chromosome. A three-Mb segment on both chromosomes resulted from a duplication 7.7 million years ago (mya), the most recent large-scale duplication in the rice genome. Paralogous gene copies within this segmental duplication can be aligned with genomic assemblies from sorghum and maize. Although these gene copies are preserved on both chromosomes, their expression patterns have diverged. When the gene order of rice chromosomes 11 and 12 was compared to wheat gene loci, significant synteny between these orthologous regions was detected, illustrating the presence of conserved genes alternating with recently evolved genes. Conclusion: Because the resistance and defense response genes, enriched on these chromosomes relative to the whole genome, also occur in clusters, they provide a preferred target for breeding durable disease resistance in rice and the isolation of their allelic variants. The recent duplication of a large chromosomal segment coupled with the high density of disease resistance gene clusters makes this the most recently envolved part of the rice genome. Based on syntenic alignments of these chromosomes, rice chromosome 11 and 12 do not appear to have resulted from a single whole-genome duplication event as peviously suggested