Objective: It is unclear if a low or high-volume intravenous (IV) fluid resuscitation strategy is better for patients with severe sepsis and septic shock. Design: Prospective randomized controlled trial. Setting: Two adult acute care hospitals within a single academic system. Patients: Patients with severe sepsis and septic shock admitted from the emergency department to the intensive care unit (ICU) from November 2016 to February 2018. Interventions: Patients were randomly assigned to a restrictive IV fluid resuscitation strategy (≤ 60ml/kg of IV fluid) or usual care for the first 72 hours of care. Measurements and Main Results: We enrolled 109 patients, of whom 55 were assigned to the restrictive resuscitation group and 54 to the usual care group. The restrictive group received

DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5′ or 3′ guanine in runs of guanines to mimic oxidative effects. We showed that DNA occupancy of NF-κB present in nuclear extracts from tumour necrosis factor alpha (TNFα) exposed cells is OGG1 and 8-oxoG position dependent, importantly, OGG1 counteracting 8-oxoG outside consensus motif had a profound influence on purified NF-κB binding to DNA. Furthermore, OGG1 is essential for NF-κB dependent gene expression, prior to 8-oxoG excised from DNA. These observations imply that pre-excision step(s) during OGG1 initiated BER evoked by ROS facilitates NF-κB DNA occupancy and gene expression.

Background The large volume and suboptimal image quality of portable chest X-rays (CXRs) as a result of the COVID-19 pandemic could post significant challenges for radiologists and frontline physicians. Deep-learning artificial intelligent (AI) methods have the potential to help improve diagnostic efficiency and accuracy for reading portable CXRs. Purpose The study aimed at developing an AI imaging analysis tool to classify COVID-19 lung infection based on portable CXRs. Materials and methods Public datasets of COVID-19 (N = 130), bacterial pneumonia (N = 145), non-COVID-19 viral pneumonia (N = 145), and normal (N = 138) CXRs were analyzed. Texture and morphological features were extracted. Five supervised machine-learning AI algorithms were used to classify COVID-19 from other conditions. Two-class and multi-class classification were performed. Statistical analysis was done using unpaired two-tailed t tests with unequal variance between groups. Performance of classification models used the receiver-operating characteristic (ROC) curve analysis. Results For the two-class classification, the accuracy, sensitivity and specificity were, respectively, 100%, 100%, and 100% for COVID-19 vs normal; 96.34%, 95.35% and 97.44% for COVID-19 vs bacterial pneumonia; and 97.56%, 97.44% and 97.67% for COVID-19 vs non-COVID-19 viral pneumonia. For the multi-class classification, the combined accuracy and AUC were 79.52% and 0.87, respectively. Conclusion AI classification of texture and morphological features of portable CXRs accurately distinguishes COVID-19 lung infection in patients in multi-class datasets. Deep-learning methods have the potential to improve diagnostic efficiency and accuracy for portable CXRs.

Pneumonia causes short‐ and long‐term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia‐elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long‐term potentiation; and, (3) inhibit long‐term potentiation dependent upon tau. Cytotoxic amyloid and tau species were recovered from the blood and the hippocampus following pneumonia, and they were present in the extracorporeal membrane oxygenation oxygenators of patients with pneumonia, especially in those who died. Introduction of immunopurified blood‐borne amyloid and tau into either the airways or the blood of uninfected animals acutely and chronically impaired hippocampal information processing. In contrast, the infection did not impair long‐term potentiation in tau knockout mice and the amyloid‐ and tau‐dependent disruption in hippocampal signaling was less severe in tau knockout mice. Moreover, the infection did not elicit cytotoxic amyloid and tau variants in tau knockout mice. Therefore, pneumonia initiates a tauopathy that contributes to cognitive dysfunction.