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A series of 4, 4-disubstituted proline analogs were designed, synthesized, and tested for selective inhibition of blood coagulation factor XIa in search of new non-vitamin K antagonists based oral anticoagulants for potential prevention and treatment of thrombotic diseases. Starting from a potent thrombin (FIIa) inhibitor chemotype with FIIa IC50 = 1 nM and FXIa IC50 = 160 nM, medicinal chemistry iterations guided by molecular modeling and structure-based drug design led to steady improvement of FXIa potency while dialing down thrombin activity and improving selectivity. Through this exercise, a thousand-fold enhancement of selectivity over thrombin was achieved with some analogs carrying factor XIa inhibition potencies in the 10 nM range. In this communication, we discuss the design principles and structure activity relationship (SAR) of these novel FXIa selective inhibitors. INTRODUCTION Burn wound infections result in delayed healing and increased pain, scarring, sepsis risk and healthcare costs. Clinical decision making about burn wound infection should be supported by evidence syntheses. Validity of evidence from systematic reviews may be reduced if definitions of burn wound infectionvary between trials. This review aimed to determine whether burn wound infectionis defined, and whether there is variation in the indicators used to define burn wound infectionacross studies testing interventions for patients with burns. METHOD Searches were carried out in four databases (Ovid Medline, Ovid Embase, Cinahl, Cochrane Register of Trials) to identify studies evaluating interventions for patients with burns and reporting a burn wound infection outcome. Pre-defined inclusion and exclusion criteria were systematically applied to select relevant studies. Data were systematically extracted and reported narratively. RESULTS 2056 studies were identified, of which 72 met the inclusion criteriinfection outcomes, a definition of this outcome is commonly not provided, or it varies between studies. This will prevent evidence synthesis to identify effective treatments for patients with burn injuries. Since there is no objective method for assessing burn wound infection, expert consensus is needed to agree a minimum set of indicators (Core Indicator Set) reported in all trials reporting burn wound infection as an outcome. BACKGROUND Acute respiratory failure survivors experience depression symptoms and new impairments in physical function. Behavioural activation, an evidence-based nonpharmacological treatment for depression, combined with physical rehabilitation, is a promising intervention. EGFR tumor Notably, mHealth applications (Apps) are potentially effective methods of delivering home-based interventions. OBJECTIVES The objective of this study was to evaluate the usability and acceptability of a prototype App to deliver a combined, home-based behavioural activation and rehabilitation intervention to acute respiratory failure survivors. METHODS A prospective user-preference study was conducted with acute respiratory failure survivors and self-designated care partners. Survivors were adults with at least mild depression symptoms before hospital discharge who received mechanical ventilation in the intensive care unit for ≥24 h. Survivors and care partners reviewed the App during a single in-person home visit and completed the System Usability Scale (range 0-100; score >73 considered "good") and a semistructured interview. RESULTS Ten patient/care partner dyads completed study. The median [interquartile range] patient age was 50 [40-64] years, and 50% were female. The median System Usability Scale scores among patients and care partners were 76 [68-83] and 88 [75-94], respectively. Qualitative feedback supported usability and acceptability of the App, with three themes reported (1) stigma associated with depression, (2) App as a motivator for recovery, and (3) App providing multidisciplinary support for survivor and care partner. CONCLUSIONS A mobile App prototype designed to deliver a combined behavioural activation and rehabilitation intervention was usable and acceptable to survivors of acute respiratory failure and their care partners. Given the reported stigma associated with depression, the self-directed App may be particularly valuable for motivation and multidisciplinary support. BACKGROUND Vitros ECiQ and Architect i2000 SR are two automated instruments used to detect serology biomarkers of hepatitis A, B and C viruses, and HIV infections. We compared performance of the Architect to the Vitro EciQ after implementation at our institution. METHODS A retrospective review was performed to compare patient samples tested on the Vitros ECiQ or Architect for hepatitis and HIV serological assays. The positivity rate, frequency of equivocal results, turnaround times (TAT), and hands-on time (HOT) were analyzed. RESULTS There was no statistical difference in the positivity rate between the two instruments, with the exception of two assays. An increase in equivocal results was observed for the Architect (0.2% vs 0.5%). Notably, the TAT for the Architect i2000 was shorter for all except one assay (31.6 vs 33.7 hours) and demonstrated improved workflow. CONCLUSIONS Overall, both instruments performed comparably. Architect had shorter TAT over Vitros. Angiari et al. recently reported that TEPP-46 induces PKM2 tetramerization, thereby inhibiting its nuclear translocation and suppressing CD4+ T cell activation, T helper (Th)1/Th17 cell development, and experimental autoimmune encephalomyelitis (EAE) development both in vitro and in vivo. Moreover, TEPP-46 suppresses T cell glycolysis. These findings identify PKM2 tetramerization as a potential therapeutic target. INTRODUCTION This study aimed to present a novel dynamic navigation method to attain minimally invasive access cavity preparations and to evaluate its 3-dimensional (3D) accuracy in locating highly difficult simulated calcified canals among maxillary and mandibular teeth. METHODS Three identical sets of maxillary and mandibular 3D-printed jaw models composed of 84 teeth in their anatomic locations with simulated calcified canals (N = 138 canals) were set up on dental manikins. The Navident dynamic navigation system (ClaroNav, Toronto, Ontario, Canada) was used to plan and execute access preparations randomly with high-speed drills by a board-certified Endodontist. Two-dimensional (2D) and 3D horizontal, vertical, and angulation discrepancies between the planned and placed access preparations were digitally measured using superimposed cone-beam computed tomographic scans. Analysis of covariance models were used to evaluate the associations and the interaction between tooth type and jaw, the canal orifice depth, and the discrepancies between planned and prepared access cavities.