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Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss. This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed. In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10–2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23–0·42, p<0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733–910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08–3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67–26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50–122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45–5·37) and persistent renal dysfunction (OR 3·82, 1·32–11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76–2·39 and persistent renal dysfunction OR 1·05, 0·12–9·45). Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective. No study funding.

Emily Ogden, author of Credulity; A Cultural History of US Mesmerism and Associate Professor of English at the University of Virginia, tackles the closely related topic of believability (or gullibility) in the late 18th and 19th centuries by fusing the uneven advance of secularization with a second body of sociological work addressing the enchantment-disenchantment process. First introduced by Max Weber, this modernization meta-narrative - if you will - involves liberating the person from enthrallment in fictitious beliefs. Stone, a reportedly hard-nosed public skeptic was \"converted\" to the power of animal magnetism by way of Brackett's memorable psychic - or in the parlance of the day, magnetic - abilities. A former medical student of French Colonial Creole descent whose family owned a Guadeloupe sugar plantation, Poyen, unexpectedly became the transmitter of French mesmerism to the U.S. In 1836, at the tender age of 22, he induced great interest in animal magnetism among elites in Boston and Providence, thus putting mesmerism on the map in America.

NLRP3-inflammasome-driven inflammation is involved in the pathogenesis of a variety of diseases. Identification of endogenous inflammasome activators is essential for the development of new anti-inflammatory treatment strategies. Here, we identified that apolipoprotein C3 (ApoC3) activates the NLRP3 inflammasome in human monocytes by inducing an alternative NLRP3 inflammasome via caspase-8 and dimerization of Toll-like receptors 2 and 4. Alternative inflammasome activation in human monocytes is mediated by the Toll-like receptor adapter protein SCIMP. This triggers Lyn/Syk-dependent calcium entry and the production of reactive oxygen species, leading to activation of caspase-8. In humanized mouse models, ApoC3 activated human monocytes in vivo to impede endothelial regeneration and promote kidney injury in an NLRP3- and caspase-8-dependent manner. These data provide new insights into the regulation of the NLRP3 inflammasome and the pathophysiological role of triglyceride-rich lipoproteins containing ApoC3. Targeting ApoC3 might prevent organ damage and provide an anti-inflammatory treatment for vascular and kidney diseases. Overabundance of apolipoprotein C3 (ApoC3) is associated with atherosclerosis. Speer and colleagues demonstrate that ApoC3 activates the NLRP3 inflammasome via a non-canonical pathway contributing to inflammation and development of atherosclerosis.

In the context of internal medicine, “triage” is a newly popularized term that refers to constellation of activities related to determining the most appropriate disposition plans for patients, including assessing patients for admissions into the inpatient medicine service. The physician or “triagist” plays a critical role in the transition of care from the outpatient to the inpatient settings, yet little literature exists addressing this particular transition. The importance of this set of responsibilities has evolved over time as health systems become increasingly complex to navigate for physicians and patients. With the emphasis on hospital efficiency metrics such as emergency department throughput and appropriateness of admissions, this type of systems-based thinking is a necessary skill for practicing contemporary inpatient medicine. We believe that triaging admissions is a critical transition in the care continuum and represents an entrustable professional activity that integrates skills across multiple Accreditation Council for Graduate Medical Education (ACGME) competencies that internal medicine residents must master. Specific curricular competencies that address the domains of provider, system, and patient will deliver a solid foundation to fill a gap in skills and knowledge for the triagist role in IM residency training.

Mast cells (MCs) and airway nerves play an important role in allergic asthma. However, little is known about the MCs and their interaction with airway nerves during allergic airway inflammation. This study aims to investigate the distribution and proliferation of MC populations in different lung compartments, along with the association of mast cells with nerve endings, using a house dust mite (HDM) model for allergic airway inflammation. BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. Immunofluorescence and Edu stains were used to examine the colocalisation of MCs and nerves and the proliferation of MCs, respectively. HDM treatment caused an increased migration of MCs into bronchi, alveolar parenchyma and airway vessels. The proportions of tryptase-chymase expressing MC (MC TC ) increased significantly in the bronchi and the alveolar parenchyma but not in the vascular tissues, by allergic airway inflammation. The association of MCs with nerves was found only in the bronchi and there were no changes in comparison of controls to HDM-treated animals. The present study shows a strong migration of tryptase expressing MC (MC T ) and MC TC into the bronchi and the alveolar parenchyma, as well as of MC T in the vascular compartment under HDM treatment. This supports the hypothesis that these mast cell populations may contribute to allergic airway inflammation.

Chemical studies toward the synthesis of an angiogenesis inhibitor azaspirene is described. There is a need for a concise and scalable asymmetric synthesis of azaspirene. The current strategy employed can lead to the production of small libraries of azaspirene derivatives and other members of the pseurotin family, where structure activity relationship (SAR) studies can be conducted in anticipation of creating innovative and more effective anti-cancer drugs. Amino acids as well as other optically active compounds make great raw materials for the synthesis of asymmetric products with deliberate stereocontrol. Numerous synthetic routes for the synthesis of azaspirene are presented with the latest strategy starting from optically active malic acid showing the most viability. Azaspirene has a highly oxygenated complex spirocyclic structure that poses abundant synthetic challenges which are addressed herein. D-Malic acid is made by the double inversion of D-aspartic acid and the stereocenter is preserved throughout the synthesis. Cyclization to the succinimide derivative forms the lactam present in azaspirene. An aldol reaction and subsequent DMP oxidation form the 1,3-diketone necessary for an asymmetric palladium-mediated -hydroxylation reaction. The chiral alcohol will be used as the oxygen in the β-oxygenated enone ring after Margaretha cyclization using a highly functionalized ester to add the diene tail of azaspirene. The benzyl group found in azaspirene will be added via a Grignard reaction at a late stage in the synthesis allowing for diversity. The synthesis of a small set of 2-amino-benzimidazole compounds that bind a RNA construct of the hepatitis C virus (HCV) internal ribosome entry site (IRES) with ligand affinity in the submicro-molar range is described. The binding interaction is demonstrated by a 2.2Å resolution crystal structure of a 2-amino-benzimidazole compound bound to the RNA construct published by the Bergdahl group with collaborators. The total synthesis and crystal structure were used to guide the production of novel compounds, and the results presented herein will influence the design and construction of novel inhibitors expected to increase potency against HCV.