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  1. Fulltext Efficacy of early initiation of ivabradine treatment in patients with acute heart failure: rationale and design of SHIFT-AHF trial
    Su Y, Ma T, Wang Z, Dong B, Tai C, Wang H, et al.
    ESC Heart Fail, 2020 Dec;7(6):4465-4471.
    PMID: 32945150 DOI: 10.1002/ehf2.12997
    AIMS: Elevated heart rate (HR) in heart failure (HF) is associated with worse outcomes, particularly in acute HF (AHF). HR reduction with ivabradine reduces cardiovascular events in HF patients with reduced ejection fraction. The present trial aimed to test the hypothesis that the early HR reduction using ivabradine improves clinical outcomes in patients with AHF.

    METHODS AND RESULTS: SHIFT-AHF is a prospective, multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of ivabradine when adding to standard therapy in AHF patients (SHIFT-AHF). The trial will include 674 AHF patients with left ventricular ejection fraction 

  2. Fulltext Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs
    El Hamdaoui Y, Zheng F, Fritz N, Ye L, Tran MA, Schwickert K, et al.
    Mol Psychiatry, 2022 Dec;27(12):5070-5085.
    PMID: 36224261 DOI: 10.1038/s41380-022-01804-3
    St. John's wort is an herb, long used in folk medicine for the treatment of mild depression. Its antidepressant constituent, hyperforin, has properties such as chemical instability and induction of drug-drug interactions that preclude its use for individual pharmacotherapies. Here we identify the transient receptor potential canonical 6 channel (TRPC6) as a druggable target to control anxious and depressive behavior and as a requirement for hyperforin antidepressant action. We demonstrate that TRPC6 deficiency in mice not only results in anxious and depressive behavior, but also reduces excitability of hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Using electrophysiology and targeted mutagenesis, we show that hyperforin activates the channel via a specific binding motif at TRPC6. We performed an analysis of hyperforin action to develop a new antidepressant drug that uses the same TRPC6 target mechanism for its antidepressant action. We synthesized the hyperforin analog Hyp13, which shows similar binding to TRPC6 and recapitulates TRPC6-dependent anxiolytic and antidepressant effects in mice. Hyp13 does not activate pregnan-X-receptor (PXR) and thereby loses the potential to induce drug-drug interactions. This may provide a new approach to develop better treatments for depression, since depression remains one of the most treatment-resistant mental disorders, warranting the development of effective drugs based on naturally occurring compounds.
  3. International Alliance of Urolithiasis (IAU) guideline on staghorn calculi management
    Zhong W, Osther P, Pearle M, Choong S, Mazzon G, Zhu W, et al.
    World J Urol, 2024 Mar 25;42(1):189.
    PMID: 38526675 DOI: 10.1007/s00345-024-04816-6
    BACKGROUND: The stone burden based management strategy reported in the guidelines published by different associations is well known for a long time. Staghorn calculi, representing the largest burden and most complex stones, is one of the most challenging cases to practicing urologists in clinical practice. The International Alliance of Urolithiasis (IAU) has released a series of guidelines on the management of urolithiasis.

    PURPOSE: To develop a series of recommendations for the contemporary management management of staghorn calculi and to provide a clinical framework for urologists treating patients with these complex stones.

    METHODS: A comprehensive literature search for articles published in English between 01/01/1976 and 31/12/2022 in the PubMed, OVID, Embase and Medline database is performed. A series of recommendations are developed and individually graded following the review of literature and panel discussion.

    RESULTS: The definition, pathogenesis, pathophysiology, preoperative evaluation, intraoperative treatment strategies and procedural advice, early postoperative management, follow up and prevention of stone recurrence are summarized in the present document.

    CONCLUSION: A series of recommendations regarding the management of staghorn calculi, along with related commentary and supporting documentation offered in the present guideline is intended to provide a clinical framework for the practicing urologists in the management of staghorn calculi.

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