University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients.

Abstract: Background: The pathophysiology of pulmonary contusion (PC) is poorly understood, and only minimal advances have been made in management of this entity over the past 20 years. Improvement in understanding of PC has been hindered by the fact that there has been no accurate way to quantitate the amount of pulmonary injury. With this project, we examine a method of accurately measuring degree of PC by quantifying contusion volume relative to pulmonary function and outcome. Methods: Patients with PC from isolated chest trauma who had admission chest computed tomographic scan were identified from the registry of a Level I trauma center over a 1.5-year period. Subsequently, prospective data on all patients admitted to the intensive care unit with PC during a 5-month period were collected and added to the retrospective database. Using computer-generated three-dimensional reconstruction from admission chest computed tomographic scan, contusion volume was measured and expressed as a percentage of total lung volume. Admission pulmonary function variables (Pao 2 /FiO 2 , static compliance), injury descriptors (chest Abbreviated Injury Score, Injury Severity Score, injury distribution), and indicators of degree of shock (admission systolic blood pressure, admission base deficit) were documented. Outcomes included maximum positive end-expiratory pressure, ventilator days, pneumonia, and acute respiratory distress syndrome (ARDS). Results: Forty-nine patients with PC (35 bilateral) were identified. The average severity of contusion was 18% (range, 5-55%). Patients were classified using contusion volume as severe PC (≥20%, n = 17) and moderate PC (<20%, n = 32). Injury Severity Score was similar in the severe and moderate groups (23.3 vs. 26.5, p = 0.33), as were admission Glasgow Coma Scale score (12 vs. 13, p = 0.30), admission blood pressure (131 vs. 129 mm Hg, p = 0.90), and admission Pao 2 /FIo 2 (197 vs. 255, p = 0.14). However, there was a much higher rate of ARDS in the severe group as compared with the moderate group (82% vs. 22%, p < 0.001). There was a trend toward higher pneumonia rate in the severe group, with 50% of patients in the severe group developing pneumonia as compared with 28% in the moderate group (p = 0.20). Conclusion: Extent of contusion volumes measured using three-dimensional reconstruction allows identification of patients at high risk of pulmonary dysfunction as characterized by development of ARDS. This method of measurement may provide a useful tool for the further study of PC as well as for the identification of patients at high risk of complications at whom future advances in therapy may be directed.

TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines.

Abstract: The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for β-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of β-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic. The innate sensors of SARS-CoV-2 are still being determined. Kanneganti and colleagues find that SARS-CoV-2 envelope protein is sensed by TLR2 and this drives pathogenic inflammatory cytokine production.

Positional cloning of a novel gene on chromosome 16q causing Bardet–Biedl syndrome (BBS2)

Abstract: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder with the primary clinical features of obesity, pigmented retinopathy, polydactyly, hypogenitalism, mental retardation and renal anomalies. Associated features of the disorder include diabetes mellitus, hypertension and congenital heart disease. There are six known BBS loci, mapping to chromosomes 2, 3, 11, 15, 16 and 20. The BBS2 locus was initially mapped to an 18 cM interval on chromosome 16q21 with a large inbred Bedouin kindred. Further analysis of the Bedouin population allowed for the fine mapping of this locus to a 2 cM region distal to marker D16S408. Physical mapping and sequence analysis of this region resulted in the identification of a number of known genes and expressed sequence tag clusters. Mutation screening of a novel gene (BBS2) with a wide pattern of tissue expression revealed homozygous mutations in two inbred pedigrees, including the large Bedouin kindred used to initially identify the BBS2 locus. In addition, mutations were found in three of 18 unrelated BBS probands from small nuclear families.

Oral GS-5806 activity in a respiratory syncytial virus challenge study

Abstract: Background Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and is increasingly recognized as a cause of considerable morbidity and mortality. No accepted antiviral treatment exists. Methods We conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry inhibitor, in healthy adults who received a clinical challenge strain of RSV intranasally. Participants were monitored for 12 days. At the time of a positive test for RSV infection or 5 days after inoculation, whichever occurred first, participants were randomly assigned to receive GS-5806 or placebo in one of seven sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days. Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of...