Publications by authors named "T Markham"

Background: The difficult airway is frequently encountered across many scenarios. The extreme form is a "cannot intubate and cannot oxygenate" scenario, which lacks a reliable rescue technique. Previous case reports or studies with small sample sizes indicate the feasibility and efficiency of an endotracheal tube in the pharynx (TTIP) to ventilate patients.

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The trihydroxamic acid bacterial siderophore desferrioxamine B (DFOB, 1) produced by the DesABCD biosynthetic cluster coordinates metals beyond Fe(iii), which identifies potential to modify this chelator type to broaden metal sequestration and/or delivery applications. Rather than producing discrete chelators by total chemical synthesis from native monomers including -hydroxy--succinyl-cadaverine (HSC, 2), the recombinant siderophore synthetase from CNB-440 (DesD) was used with different substrate combinations to produce biocombinatorial mixtures of hydroxamic acid chelators. The mixtures were screened with Ga(iii) or Zr(iv) as surrogates of immunological positron emission tomography (PET) imaging radiometals Ga(iii) or Zr(iv) to inform known or new coordination chemistry.

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A mild and modular approach to the total synthesis of the WHO-listed essential medicine desferrioxamine B is described. Hydroxamic acid fragments were installed under mild conditions, a generalized divergent acylation procedure used to access two monomer precursors, and a transfer hydrogenation reaction used to unmask the hydroxamic acid moieties. Desferrioxamine B was generated over ten linear steps as the formate salt in 17% overall yield using standard amide coupling conditions or in 13% overall yield using microwave-assisted amide coupling conditions.

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Article Synopsis
  • Researchers created two types of resins using desferrioxamine B (DFOB), one as a free ligand and the other with its Fe(iii) complex, to identify proteins linked to iron uptake through siderophores.
  • Despite extensive analysis, no proteins associated with Fe(iii) uptake were found, but nickel superoxide dismutase (NiSOD) was discovered to be preferentially bound to the apo-DFOB resin.
  • The study suggests that DFOB can form a complex with NiSOD, indicating that the metal-binding properties of siderophores may affect various biological functions beyond just iron acquisition.
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Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.

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