Mycobacterium tuberculosis Rv3802c Encodes a Phospholipase/Thioesterase and Is Inhibited by the Antimycobacterial Agent Tetrahydrolipstatin

The cell wall of M. tuberculosis is central to its success as a pathogen. Mycolic acids are key components of this cell wall. The genes involved in joining the α and mero mycolates are located in a cluster, beginning with Rv3799c and extending at least until Rv3804c. The role of each enzyme encoded by these five genes is fairly well understood, except for Rv3802c. Rv3802 is one of seven putative cutinases encoded by the genome of M. tuberculosis. In phytopathogens, cutinases hydrolyze the waxy layer of plants, cutin. In a strictly mammalian pathogen, such as M. tuberculosis, it is likely that these proteins perform a different function. Of the seven, we chose to focus on Rv3802c because of its location in a mycolic acid synthesis gene cluster, its putative essentiality, its ubiquitous presence in actinomycetes, and its conservation in the minimal genome of Mycobacterium leprae. We expressed Rv3802 in Escherichia coli and purified the enzymatically active form. We probed its activities and inhibitors characterizing those relevant to its possible role in mycolic acid biosynthesis. In addition to its reported phospholipase A activity, Rv3802 has significant thioesterase activity, and it is inhibited by tetrahydrolipstatin (THL). THL is a described anti-tuberculous compound with an unknown mechanism, but it reportedly targets cell wall synthesis. Taken together, these data circumstantially support a role for Rv3802 in mycolic acid synthesis and, as the cell wall is integral to M. tuberculosis pathogenesis, identification of a novel cell wall enzyme and its inhibition has therapeutic and diagnostic implications

Evaluation of young smokers and non-smokers with Electrogustometry and Contact Endoscopy

<p>Abstract</p> <p>Background</p> <p>Smoking is the cause of inducing changes in taste functionality under conditions of chronic exposure. The objective of this study was to evaluate taste sensitivity in young smokers and non-smokers and identify any differences in the shape, density and vascularisation of the fungiform papillae (fPap) of their tongue.</p> <p>Methods</p> <p>Sixty-two male subjects who served in the Greek military forces were randomly chosen for this study. Thirty-four were non-smokers and 28 smokers. Smokers were chosen on the basis of their habit to hold the cigarette at the centre of their lips. Taste thresholds were measured with Electrogustometry (EGM). The morphology and density of the fungiform papillae (fPap) at the tip of the tongue were examined with Contact Endoscopy (CE).</p> <p>Results</p> <p>There was found statistically important difference (<it>p </it>< 0.05) between the taste thresholds of the two groups although not all smokers presented with elevated taste thresholds: Six of them (21%) had taste thresholds similar to those of non-smokers. Differences concerning the shape and the vessels of the fungiform papillae between the groups were also detected. Fewer and flatter fPap were found in 22 smokers (79%).</p> <p>Conclusion</p> <p>The majority of smokers shown elevated taste thresholds in comparison to non-smokers. Smoking is an important factor which can lead to decreased taste sensitivity. The combination of methods, such as EGM and CE, can provide useful information about the vascularisation of taste buds and their functional ability.</p

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

A First-Year DPT Student’s Perspectives on a Cadaver with Scoliosis

Study Design: Single subject observational case report. Background: Scoliosis is a condition commonly managed by physical therapists (PTs) in most settings. Patient management may include surgical correction, which requires PTs to be knowledgeable of the type of surgery and implications. Recent orthopedic research has found that disease type may alter vertebral anatomy, indicating the need for further consideration of the surgical technique used.4. Case Description: Measurements of vertebral anatomy of a human cadaver were obtained by bisection of the vertebra, then compared with measurements from magnetic resonance (MR) images in previously reported orthopedic studies. The purpose of this study was to explore and combine the literature review with examination of a human specimen to gain a deeper understanding of scoliotic anatomy in order to enhance future clinical practice as well as to attempt to identify the underlying condition that led to scoliosis and other impairments in the cadaver. Outcomes: This study led to a hypothesis of etiology of scoliosis in the cadaver by comparison of physical measurements to existing studies and synthesis of existing research. Cadaveric measurements generally matched corresponding measurements of idiopathic scoliosis as described in previous studies. Analysis of the global abnormalities of the cadaver led to a clinically applicable understanding of the end-stage of life presentation of scoliosis and the necessity of management of this condition. Conclusion: According to research, the spinal column in patients with scoliosis may differ anatomically based on disease. This study, by improving one student’s knowledge of scoliosis, raised the question of whether PTs should base management decisions of scoliosis on etiology due to the anatomical differences. The opportunistic approach to this study shows the importance of students’ willingness to explore disease processes that may be present in the cadaver population within the anatomy laboratory