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Objectives: This study aimed to describe characteristics and outcomes associated with difficult airway response team (DART) encounters in the emergency department (ED)., Methods: We performed a descriptive analysis of a prospective, single-center database of DART encounters in the ED from April 1, 2016 to March 31, 2021 cross-referenced with retrospective chart review. Adult ED patients ≥18 years old for whom a DART was activated were eligible. We prospectively collected activation characteristics, intubation indications, operator characteristics, and intubation methods used for DART encounters. Retrospective chart review was conducted to obtain patient demographics and outcome variables. Descriptive analyses were computed for all outcomes., Results: We analyzed 89 DART encounters. No intubation attempts were made prior to DART activation in 52 cases (58.4%). The most common indications for intubation were angioedema ( n  = 17, 19.1%) or other airway obstruction ( n  = 15, 16.9%). A definitive airway was established by anesthesiology ( n  = 46, 51.7%), emergency medicine ( n  = 25, 28.1%), trauma surgery ( n  = 9, 10.1%), and ENT ( n  = 5, 5.6%). The most common method of intubation used to establish a definitive airway was video laryngoscopy with a bougie or D-blade ( n  = 29, 32.6%) followed by flexible fiberoptic intubation ( n  = 19, 21.3%). A surgical airway was required in eight encounters (cricothyrotomy [ n  = 4, 4.5%]; tracheostomy [ n  = 4, 4.5%]). Cases were managed in the ED ( n  = 73, 82%), operating room (OR) ( n  = 10, 11.2%), and intensive care unit (ICU) ( n  = 1, 1.1%). All patients requiring intubation had an endotracheal or surgical airway established., Conclusion: Our findings provide important insights regarding ED DART utilization and have implications when considering institution of a DART in the ED., Competing Interests: Rosemarie Fernandez reports grant funding from the Defense Health Agency and the National Science Foundation. Nicholas G. Maldonado, Meredith Thompson, Caroline Srihari, Liam Holtzman, Jonathan Liu, Rolando Otero, and Muhammad Abdul Baker Chowdhury have no conflicts of interest to report., (© 2024 The Authors. Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions., Competing Interests: None., (© 2023 The Authors.)

Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable., Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2 nd /3 rd -generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT). Patients were divided into groups: patients in whom the NLST was initiated after (group 1) and before (group 2) receival of the CGP results. Time-to-treatment discontinuation (TTD) and overall survival (OS) with NLST were compared between the groups., Results: In 20 eligible patients (median [m]age 63 years [range, 40-89], females 75%, adenocarcinoma 100%, failure of alectinib 90%, FoundationOne Liquid CDx 80%), CGP has altered NLST recommendation in 30% of cases. CGP findings were as follows: ALK mutations 30% (l1171X 10%, G1202R, L1196M, G1269A, G1202R+l1171N+E1210K 5% each), CDKN2A/B mutation/loss 10%, c-met amplification 5%. CGP mTAT was 2.9 weeks [IQR, 2.4-4.4]. mTTD was 11.3 months (95% CI, 2.1-not reached [NR]) and 5.4 months (95% CI, 2.0-NR) in groups 1 and 2, respectively (p-0.34). mOS was 13.2 months (95% CI, 2.9-NR) and 13.0 months (95% CI, 6.0-NR) in groups 1 and 2, respectively (p-0.86)., Conclusion: CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2 nd /3 rd -generation ALK TKIs., Competing Interests: Author TS was employed by the company Statistical Consulting Unit. Disclosure (all outside of the submitted work): AR reported personal fees from Roche, Astra Zeneca, Merck Sharpe & Dohme, Novartis, Takeda, Elli Lilly, support for attending meetings from Bristol Myers Squibb, Roche, Boehringer Ingelheim. AO reported advisory fees from Merck Sharpe & Dohme, Bristol Myers Squibb, Roche, Astra Zeneca, Novartis, Boehringer Ingelheim. Damien Urban reported personal and consulting fees from Roche, Merck Sharpe & Dohme, Takeda, Astra Zeneca, Rhenium Oncotest, Bristol Myers Squibb. MM reported consulting fees from Boehringer Ingelheim, Roche, Astra Zeneca, MSD, BMS, Abbvie, Takeda, Pomicell. AZ reported grants from Bristol Myers Squibb, personal fees from Roche, Merck Sharpe & Dohme, Bristol Myers Squibb, Astra Zeneca, Takeda. JB reported grants and personal fees from Merck Sharpe & Dohme, Bristol Myers Squibb, Astra Zeneca, Roche, Abbvie, Takeda, OncoHost, ImmuneAI, Bayer, Novartis. AA reported research funding from Bristol Myers Squibb, personal and consulting fees from Bristol Myers Squibb, Roche, Pfizer, Astra Zeneca, Takeda, Novartis. NP reported research funding from Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merk, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda, IP: Volatile Organic Compounds For Detecting Cell Dysplasia And Genetic Alterations Associated With Lung Cancer, WO2012023138; Breath Analysis of Pulmonary Nodules, US20130150261 A1; Apparatus for treating a target site of a body, WO/2015/059646 - all outside of the submitted work. ED reported grants from Astra Zeneca, Boehringer Ingelheim, personal fees from Boehringer Ingelheim, Roche, Astra Zeneca, Pfizer, Merck Sharpe & Dohme, Bristol Myers Squibb, Novartis, Takeda, Sanofi, Merck Serono, Medison Pharma, Janssen Israel- all outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Raphael, Onn, Holtzman, Dudnik, Urban, Kian, Cohen, Moskovitz, Zer, Bar, Rabinovich, Grynberg, Oedegaard, Agbarya, Peled, Shochat and Dudnik.)

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to show that Fos and Npas4 are transcribed in stochastic bursts in mouse neurons and that membrane depolarization increases mRNA expression by increasing burst frequency. We then expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. Inhibiting histone acetylation reduced Fos transcription by reducing burst frequency and impaired experience-dependent Fos protein induction in the hippocampus in vivo. Thus, activity-inducible histone acetylation tunes the transcriptional dynamics of experience-regulated genes to affect selective changes in neuronal gene expression and cellular function., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Behavioral and psychological symptoms of dementia are common in nursing home residents, and the Centers for Medicare and Medicaid Services now require that nonpharmacological interventions be used as a first-line treatment. Few staff know how to implement these interventions. The purpose of this study was to pilot test an implementation strategy, Evidence Integration Triangle for Behavioral and Psychological Symptoms of Dementia (EIT-4-BPSD), which was developed to help staff integrate behavioral interventions into routine care. The EIT-4-BPSD was implemented in 2 nursing homes, and 21 residents were recruited. A research nurse facilitator worked with facility champions and a stakeholder team to implement the 4 steps of EIT-4-BPSD. There was evidence of reach to all staff; effectiveness with improvement in residents' quality of life and a decrease in agitation; adoption based on the environment, policy, and care plan changes; and implementation and plans for maintenance beyond the 6-month intervention period., (© The Author(s) 2016.)

Background: Risk communication involves conveying two inherently difficult concepts about the nature of risk: the underlying random distribution of outcomes and how a population-based proportion applies to an individual., Objective: The objective of this study was to test whether 4 design factors in icon arrays-animated random dispersal of risk events, avatars to represent an individual, personalization (operationalized as choosing the avatar's color), and a moving avatar-might help convey randomness and how a given risk applies to an individual, thereby better aligning risk perceptions with risk estimates., Methods: A diverse sample of 3630 adults with no previous heart disease or stroke completed an online nested factorial experiment in which they entered personal health data into a risk calculator that estimated 10-year risk of cardiovascular disease based on a robust and validated model. We randomly assigned them to view their results in 1 of 10 risk graphics that used different combinations of the 4 design factors. We measured participants' risk perceptions as our primary outcome, as well as behavioral intentions and recall of the risk estimate. We also assessed subjective numeracy, whether or not participants knew anyone who had died of cardiovascular causes, and whether or not they knew their blood pressure and cholesterol as potential moderators., Results: Animated randomness was associated with better alignment between risk estimates and risk perceptions (F1,3576=6.12, P=.01); however, it also led to lower scores on healthy lifestyle intentions (F1,3572=11.1, P<.001). Using an avatar increased risk perceptions overall (F1,3576=4.61, P=.03) and most significantly increased risk perceptions among those who did not know a particular person who had experienced the grave outcomes of cardiovascular disease (F1,3576=5.88, P=.02). Using an avatar also better aligned actual risk estimates with intentions to see a doctor (F1,3556=6.38, P=.01). No design factors had main effects on recall, but animated randomness was associated with better recall for those at lower risk and worse recall for those at higher risk (F1,3544=7.06, P=.01)., Conclusions: Animated randomness may help people better understand the random nature of risk. However, in the context of cardiovascular risk, such understanding may result in lower healthy lifestyle intentions. Therefore, whether or not to display randomness may depend on whether one's goal is to persuade or to inform. Avatars show promise for helping people grasp how population-based statistics map to an individual case.

Induced pluripotent stem cells (iPSCs) can be derived from somatic cells by ectopic expression of different transcription factors, classically Oct4 (also known as Pou5f1), Sox2, Klf4 and Myc (abbreviated as OSKM). This process is accompanied by genome-wide epigenetic changes, but how these chromatin modifications are biochemically determined requires further investigation. Here we show in mice and humans that the histone H3 methylated Lys 27 (H3K27) demethylase Utx (also known as Kdm6a) regulates the efficient induction, rather than maintenance, of pluripotency. Murine embryonic stem cells lacking Utx can execute lineage commitment and contribute to adult chimaeric animals; however, somatic cells lacking Utx fail to robustly reprogram back to the ground state of pluripotency. Utx directly partners with OSK reprogramming factors and uses its histone demethylase catalytic activity to facilitate iPSC formation. Genomic analysis indicates that Utx depletion results in aberrant dynamics of H3K27me3 repressive chromatin demethylation in somatic cells undergoing reprogramming. The latter directly hampers the derepression of potent pluripotency promoting gene modules (including Sall1, Sall4 and Utf1), which can cooperatively substitute for exogenous OSK supplementation in iPSC formation. Remarkably, Utx safeguards the timely execution of H3K27me3 demethylation observed in embryonic day 10.5-11 primordial germ cells (PGCs), and Utx-deficient PGCs show cell-autonomous aberrant epigenetic reprogramming dynamics during their embryonic maturation in vivo. Subsequently, this disrupts PGC development by embryonic day 12.5, and leads to diminished germline transmission in mouse chimaeras generated from Utx-knockout pluripotent cells. Thus, we identify Utx as a novel mediator with distinct functions during the re-establishment of pluripotency and germ cell development. Furthermore, our findings highlight the principle that molecular regulators mediating loss of repressive chromatin during in vivo germ cell reprogramming can be co-opted during in vitro reprogramming towards ground state pluripotency.