Retinoblastoma (RB) outcomes in Thailand are unfavorable compared to those of developed countries. This study aims to determine whether the clinical outcomes of patients with RB significantly improved after the implementation of new therapeutic approaches as well as which clinical factors affect survival and globe-saving outcomes.
 
  The medical records of patients newly diagnosed with RB and treated at Siriraj Hospital between January 2005 and December 2018 were retrospectively reviewed. Clinical data, treatments, and outcomes were collected and analyzed.
 
  In 194 eyes (144 patients), leukocoria was the most common presenting feature (76.8%); 129 (66.5%) eyes were staged in group E of the International Classification of Intraocular Retinoblastoma. Of the 149 enucleated eyes, 35 had high-risk histopathological features, mostly choroidal invasion; 45 eyes (23.2%) could be salvaged. The 5-year overall survival rate was 90.3%, an improvement compared to the previous study. The 5-year enucleation-free survival rates of Groups A and B, C, D and E were 100%, 83.1%, 36.7% and 16.6% respectively. Factors associated with a lower survival rate were interval from symptom onset to diagnosis >3 months (HR 5.8 95% CI 1.637, 20.579) and buphthalmos (HR 12.57 95% CI 3.936, 40.153). Factors associated with high-risk features were secondary glaucoma (HR 11.016 95% CI 1.24, 98.10) and pseudohypopyon (HR 14.110 95%CI 2.16, 92.05).
 
  Survival rates and globe-saving rates appear to have improved; however, advanced stage presentation remain the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.
 Survival rates and globe-saving rates appear to have improved; however, advanced stage presentation remain the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.CAAC precursors 2-chloro-3,3-dimethylindole 1 and 2-chloro-1-ethyl-3,3-dimethylindolium tetrafluoroborate 2BF4 have been prepared and oxidatively added to [M(PPh3 )4 ] (M=Pd, Pt). Salt 2BF4 reacts with [Pd(PPh3 )4 ] in toluene at 25 °C over 4 days to yield complex cis-[3]BF4 featuring an N-ethyl substituted CAAC, two cis-arranged phosphines and a chloro ligand. Compound trans-[3]BF4 was obtained from the same reaction at 80 °C over 1 day. Salt 2BF4 reacts with [Pt(PPh3 )4 ] to give cis-[4]BF4 . The neutral indole derivative 1 adds oxidatively to [Pt(PPh3 )4 ] to give trans-[5] featuring a CAAC ligand with an unsubstituted ring-nitrogen atom. This nitrogen atom has been protonated with py⋅HBF4 to give trans-[6]BF4 bearing a protic CAAC ligand. The PdII complex trans-[7]BF4 bearing a protic CAAC ligand was obtained in a one-pot reaction from 1 and [Pd(PPh3 )4 ] in the presence of py⋅HBF4 .
  Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility.
 
  Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station.
 
  Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells.  https://www.selleckchem.com/products/sbfi-26.html  Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance.
 
  3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.
 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.The scaffolding protein RbAp48 is part of several epigenetic regulation complexes and is overexpressed in a variety of cancers. In order to develop tool compounds for the study of RbAp48 function, we have developed peptide inhibitors targeting the protein-protein interaction interface between RbAp48 and the scaffold protein MTA1. Based on a MTA1-derived linear peptide with low micromolar affinity and informed by crystallographic analysis, a bicyclic peptide was developed that inhibits the RbAp48/MTA1 interaction with a very low nanomolar KD value of 8.56 nM, and which showed appreciable stability against cellular proteases. Design included exchange of a polar amide cyclization strategy to hydrophobic aromatic linkers enabling mono- and bicyclization by means of cysteine alkylation, which improved affinity by direct interaction of the linkers with a hydrophobic residue on RbAp48. Our results demonstrate that stepwise evolution of a structure-based design is a suitable strategy for inhibitor development targeting PPIs.The unparalleled potential of substrate-induced reactivity modes in the catalytic conversion of carbon dioxide and alcohol or amine functionalized epoxides is discussed in relation to more conventional epoxide/CO2 coupling strategies. This conceptually new approach allows for a substantial extension of the substitution degree and functionality of cyclic carbonate/carbamate products, which are predominant products in the area of nonreductive CO2 transformations. Apart from the creation of an advanced library of CO2 -based heterocyclic products and intermediates, also the underlying mechanistic reasons for this novel reactivity profile are debated with a prominent role for the design and structure of the involved catalysts.