Highlights • Anxiety is associated with attentional bias for threatening stimuli. • Anxiety-related attentional bias for threat helps to explain ‘stiffening’ behaviors. • ‘Stiffening’ behaviors will ...only help to prevent falls during simple postural tasks. • Anxiety will compromise attentional resources required for complex locomotor tasks. • Stiffening behavior could be driven by an internal focus of attention/reinvestment.
Abstract
Background
The incidence of pneumonic tularemia is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCMs) in humans. The US ...Food and Drug Administration’s Animal Model Qualification Program under the Drug Development Tools Program is a regulatory pathway for animal models used in MCM efficacy testing and approval under the Animal Rule. The National Institute of Allergy and Infectious Diseases and Biomedical Advanced Research and Development Authority worked together to qualify the cynomolgus macaque model of pneumonic tularemia.
Methods
Using the model parameters and end points defined in the qualified model, efficacy of the antibiotics doxycycline and ciprofloxacin was evaluated in separate studies. Antibiotic administration, aimed to model approved human dosing, was initiated at time points of 24 hours or 48 hours after onset of fever as an indicator of disease.
Results
Upon aerosol exposure (target dose of 1000 colony-forming units) to Francisella tularensis SchuS4, 80% of vehicle-treated macaques succumbed or were euthanized. Ciprofloxacin treatment led to 10 of 10 animals surviving irrespective of treatment time. Doxycycline administered at 48 hours post-fever led to 10 of 10 animals surviving, while 9/10 animals survived in the group treated with doxycycline 24 hours after fever. Selected surviving animals in both the placebo and doxycycline 48-hour group showed residual live bacteria in peripheral tissues, while there were no bacteria in tissues from ciprofloxacin-treated macaques.
Conclusions
Both doxycycline and ciprofloxacin were efficacious in treatment of pneumonic tularemia, although clearance of bacteria may be different between the 2 drugs.
Managing malnutrition in COPD: A review Keogh, Emma; Mark Williams, E.
Respiratory medicine,
January 2021, 2021-01-00, 20210101, Volume:
176
Journal Article
Peer reviewed
Open access
In the UK approximately 1.2 million people have COPD with around 25–40% being underweight and 35% have a severely low fat-free mass index. Measuring their body mass index is recommended and Health ...care professionals should endeavour to ensure that COPD patients are achieving their nutritional requirements.
A narrative review summarizes evidence from 28 original articles identified through a systematic searches of databases, grey literature and hand searches covering 15 years, focusing on two themes, on the impact of malnutrition on COPD, and the management of malnutrition in COPD.
Malnutrition causes negative effects on exercise and muscle function and lung function as well as increasing exacerbations, mortality and cost. Management options include nutritional supplementation which may increase weight and muscle function. Nutritional education has short-term improvements.
Malnutrition affects multiple aspects of COPD, but treatment is of benefit. Clinical practice should include nutrition management.
Reducing rates of rehospitalization has attracted attention from policymakers as a way to improve quality of care and reduce costs. However, we have limited information on the frequency and patterns ...of rehospitalization in the United States to aid in planning the necessary changes.
We analyzed Medicare claims data from 2003-2004 to describe the patterns of rehospitalization and the relation of rehospitalization to demographic characteristics of the patients and to characteristics of the hospitals.
Almost one fifth (19.6%) of the 11,855,702 Medicare beneficiaries who had been discharged from a hospital were rehospitalized within 30 days, and 34.0% were rehospitalized within 90 days; 67.1% corrected of patients who had been discharged with medical conditions and 51.5% of those who had been discharged after surgical procedures were rehospitalized or died within the first year after discharge. In the case of 50.2% corrected of the patients who were rehospitalized within 30 days after a medical discharge to the community, there was no bill for a visit to a physician's office between the time of discharge and rehospitalization. Among patients who were rehospitalized within 30 days after a surgical discharge, 70.5% were rehospitalized for a medical condition. We estimate that about 10% of rehospitalizations were likely to have been planned. The average stay of rehospitalized patients was 0.6 day longer than that of patients in the same diagnosis-related group whose most recent hospitalization had been at least 6 months previously. We estimate that the cost to Medicare of unplanned rehospitalizations in 2004 was $17.4 billion.
Rehospitalizations among Medicare beneficiaries are prevalent and costly.
Perceptual-cognitive skills enable an individual to integrate environmental information with existing knowledge to be able to process stimuli and execute appropriate responses on complex tasks. ...Various underlying processes could explain how perceptual-cognitive skills impact on expert performance, as articulated in three theoretical accounts: (a) the long-term working memory theory, which argues that experts are able to encode and retrieve visual information from long-term working memory more than less experienced counterparts; (b) the information-reduction hypothesis, which suggests that experts can optimize the amount of information processed by selectively allocating their attentional resources to task relevant stimuli and ignore irrelevant stimuli; and (c) the holistic model of image perception, which proposes that experts are able to extract visual information from distal and para-foveal regions, allowing more efficient global-local processing of the scene. In this systematic review, we examine the validity of the aforementioned theories based on gaze features associated with the proposed processes. The information-reduction hypothesis was supported in most studies, except in medicine where the holistic model of image perception garners stronger support. These results indicate that selectively allocating attention toward important task-related information is the most important skill developed in experts across domains, whereas expertise in medicine is reflected more in an extended visual span. Large discrepancies in the outcomes of the papers reviewed suggest that there is not one theory that fits all domains of expertise. The review provides some essential building blocks, however, to help synthesize theoretical concepts across expertise domains.
Public Significance Statement
Perceptual-cognitive skills are linked to superior performance in many professional settings (e.g., radiology, aviation, football). In this systematic review, we show that experts are able to maximize their attention to relevant visual information and optimize performance in specific perceptual-cognitive tasks.
There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of ...these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA-ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed extensively with these methods. Conventional mono-intercalators and bis-intercalators are discussed, followed by unconventional DNA intercalation. We then consider the prospects for using these methods in optimizing conventional and unconventional DNA-intercalating small molecules.
Abstract
MetaboLights is a database for metabolomics studies, their raw experimental data and associated metadata. The database is cross-species and cross-technique and it covers metabolite ...structures and their reference spectra as well as their biological roles and locations. MetaboLights is the recommended metabolomics repository for a number of leading journals and ELIXIR, the European infrastructure for life science information. In this article, we describe the significant updates that we have made over the last two years to the resource to respond to the increasing amount and diversity of data being submitted by the metabolomics community. We refreshed the website and most importantly, our submission process was completely overhauled to enable us to deliver a far more user-friendly submission process and to facilitate the growing demand for reproducibility and integration with other ‘omics. Metabolomics resources and data are available under the EMBL-EBI’s Terms of Use via the web at https://www.ebi.ac.uk/metabolights and under Apache 2.0 at Github (https://github.com/EBI-Metabolights/).
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