Point-of-care ultrasound leads to a rare incidental diagnosis in a patient with acute kidney injury.

ABSTRACT: Cardiac amyloidosis is a rare disorder with a poor long-term prognosis. Presenting features often mirror those of more commonly encountered diseases, making diagnosis challenging. Clinicians should suspect amyloidosis in patients presenting with symptoms of heart failure and preserved ejection fraction. Diagnostic testing assesses for characteristic ECG, echocardiogram, and cardiovascular MRI findings. Confirmatory testing traditionally is performed with endomyocardial biopsy, but safer, less-invasive options exist. Although overall prognosis is unfavorable, contemporary advances in treatment options have improved short-term patient survival.

Direct heteroarylation polymerization: guidelines for defect-free conjugated polymers.

Direct (hetero)arylation polymerization (DHAP) has emerged as a valuable and atom-economical alternative to traditional cross-coupling methods for the synthesis of low-cost and efficient conjugated polymers for organic electronics. However, when applied to the synthesis of certain (hetero)arene-based materials, a lack of C-H bond selectivity has been observed. To prevent such undesirable side-reactions, we report the design and synthesis of new, bulky, phosphine-based ligands that significantly enhance selectivity of the DHAP process for both halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. To better understand the selectivity issues, density functional theory (DFT) calculations have been performed on various halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. Calculations showed that the presence of bromine atoms decreases the energy of activation (Ea) of the adjacent C-H bonds, allowing undesirable ß-defects for some brominated aromatic units. Both calculations and the new ligands should lead to the rational design of monomers and methods for the preparation of defect-free conjugated polymers from DHAP.

Thiophene-S,S-dioxidized Indophenine: A Quinoid-Type Building Block with High Electron Affinity for Constructing n-Type Polymer Semiconductors with Narrow Band Gaps.

Three thiophene-S,S-dioxidized indophenine (IDTO) isomers, 3 a (E,E,E), 3 b (Z,E,E), and 3 c (Z,E,Z), were synthesized by oxidation of an indophenine compound. 3 b and 3 c could be converted into the most-stable 3 a by heating at 110 °C. An IDTO-containing conjugated polymer, PIDTOTT, was prepared using 3 a as a comonomer through a Stille coupling reaction, and it possesses a narrow band gap and low energy levels. In organic field effect transistors (OFETs), PIDTOTT exhibited unipolar n-type semiconductor characteristics with unexpectedly high electron mobility (up to 0.14 cm(2) V(-1) s(-1)), despite its rather disordered chain packing.

(3E,8E)-3,8-Bis(2-oxoindolin-3-ylidene)naphtho-[1,2-b:5,6-b']difuran-2,7(3H,8H)-dione (INDF) based polymers for organic thin-film transistors with highly balanced ambipolar charge transport characteristics.

Two donor-acceptor (D-A) conjugated polymers, PINDFTT and PINDFBT, based on a novel electron acceptor, (3E,8E)-3,8-bis(2-oxoindolin-3-ylidene)naphtho-[1,2-b:5,6-b']difuran-2,7(3H,8H)-dione (INDF), are synthesized for solution processed organic thin-film transistors. Both polymers exhibited highly balanced ambipolar characteristics with hole and electron mobilities up to 0.51 cm(2) V(-1) s(-1) and 0.50 cm(2) V(-1) s(-1), respectively.

(3E,7E)-3,7-Bis(2-oxoindolin-3-ylidene)-5,7-dihydropyrrolo[2,3-f]indole-2,6(1H,3H)-dione based polymers for ambipolar organic thin film transistors.

A novel acceptor, (3E,7E)-3,7-bis(2-oxoindolin-3-ylidene)-5,7-dihydropyrrolo[2,3-f]indole-2,6(1H,3H)-dione, was reported. Donor-acceptor (D-A) polymer semiconductors using this new building block showed high ambipolar charge transport performance with hole and electron mobilities up to 0.19 and 0.09 cm(2) V(-1) s(-1), respectively, in thin film transistors.

Synthesis of 3-guaninyl- and 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone nucleosides.

L- and D-glutamic acids, as well as trans-4-hydroxy-L-proline, are converted to the corresponding 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analog. The protecting group used to block the lactam nitrogen in key intermediates has a significant effect on the diastereoselectivity of the coupling reaction with adenine or guanine.

Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants.

Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selective peptidomimetic inhibitors of FXIa were designed and synthesized. Some of these inhibitors showed low nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity and >100-fold thrombin selectivity. The X-ray structure of one of these inhibitors, 36, demonstrates its unique binding interactions with FXIa. Compound 32 caused a doubling of the activated partial thromboplastin time in human plasma at 2.4 microM and was efficacious in a rat model of venous thrombosis. These data suggest that factor XIa plays a significant role in venous thrombosis and may be a suitable target for the development of antithrombotic therapy.

Synthesis, SAR exploration, and X-ray crystal structures of factor XIa inhibitors containing an alpha-ketothiazole arginine.

Using an alpha-ketothiazole arginine moiety as a key recognition element, a series of small peptidomimetic molecules was designed and synthesized, and their co-crystal structures with factor XIa were studied in an effort to develop smaller, less peptidic inhibitors as antithrombotic agents.