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, Letnik:
176
Journal Article
Recenzirano
Odprti dostop
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.
In this analysis of 2003–2004 Medicare claims data, 20% of hospitalized patients were rehospitalized within 30 days after discharge. Fifty percent of patients who were rehospitalized after a medical ...discharge did not have an outpatient visit between discharge and readmission, raising the possibility that improved outpatient follow-up may reduce rehospitalizations.
In this analysis of Medicare claims data, 20% of hospitalized patients were rehospitalized within 30 days after discharge. Fifty percent of patients who were rehospitalized after a medical discharge did not have an outpatient visit between discharge and readmission.
Medicare currently pays for all rehospitalizations, except those in which patients are rehospitalized within 24 hours after discharge for the same condition for which they had initially been hospitalized. Recent policy proposals would alter this approach and create payment incentives to reduce the rates of rehospitalization. The Medicare Payment Advisory Commission (MedPAC) recommended to Congress in its report in June 2008 that hospitals receive from the Centers for Medicare and Medicaid Services (CMS) a confidential report of their risk-adjusted rehospitalization rates and that after 2 years, rates should be published. MedPAC also recommended complementary changes in payment rates, so that . . .
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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