Statewide retrospective study of low acuity emergency presentations in New South Wales, Australia: who, what, where and why?

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Abstract Objective The present study aims to use a statewide population-based registry to assess the prevalence of low acuity emergency department (ED) presentations, describe the trend in presentation rates and to determine whether they were associated with various presentation characteristics such as the type of hospital as well as clinical and demographic variables. Design and setting This was a retrospective analysis of a population-based registry of ED presentations in New South Wales (NSW). Generalised estimating equations with log links were used to determine factors associated with low acuity presentations to account for repeat presentations and the possibility of clustering of outcomes. Participants Patients were included in this analysis if they presented to an ED between January 2010 and December 2014. The outcomes of interest were low acuity presentation, defined as those who self-presented (were not transported by ambulance), were assigned a triage category of 4 or 5 (semiurgent or non-urgent) and discharged back to usual residence from ED. Results There were 10.7 million ED presentations analysed. Of these, 45% were classified as a low acuity presentation. There was no discernible increase in the rate of low acuity presentations across NSW between 2010 and 2014. The strongest predictors of low acuity ED presentation were age <40 years of age (OR 1.77); injury or musculoskeletal administrative and non-urgent procedures (OR 2.96); ear, nose and throat, eye or oral (OR 5.53); skin or allergy-type presenting problems (OR 2.84). Conclusions Low acuity ED presentations comprise almost half of all ED presentations. Alternative emergency models of care may help meet the needs of these patients

APOBEC3G induces a hypermutation gradient: purifying selection at multiple steps during HIV-1 replication results in levels of G-to-A mutations that are high in DNA, intermediate in cellular viral RNA, and low in virion RNA

<p>Abstract</p> <p>Background</p> <p>Naturally occurring Vif variants that are unable to inhibit the host restriction factor APOBEC3G (A3G) have been isolated from infected individuals. A3G can potentially induce G-to-A hypermutation in these viruses, and hypermutation could contribute to genetic variation in HIV-1 populations through recombination between hypermutant and wild-type genomes. Thus, hypermutation could contribute to the generation of immune escape and drug resistant variants, but the genetic contribution of hypermutation to the viral evolutionary potential is poorly understood. In addition, the mechanisms by which these viruses persist in the host despite the presence of A3G remain unknown.</p> <p>Results</p> <p>To address these questions, we generated a replication-competent HIV-1 Vif mutant in which the A3G-binding residues of Vif, Y⁴⁰RHHY⁴⁴, were substituted with five alanines. As expected, the mutant was severely defective in an A3G-expressing T cell line and exhibited a significant delay in replication kinetics. Analysis of viral DNA showed the expected high level of G-to-A hypermutation; however, we found substantially reduced levels of G-to-A hypermutation in intracellular viral RNA (cRNA), and the levels of G-to-A mutations in virion RNA (vRNA) were even further reduced. The frequencies of hypermutation in DNA, cRNA, and vRNA were 0.73%, 0.12%, and 0.05% of the nucleotides sequenced, indicating a gradient of hypermutation. Additionally, genomes containing start codon mutations and early termination codons within <it>gag </it>were isolated from the vRNA.</p> <p>Conclusion</p> <p>These results suggest that sublethal levels of hypermutation coupled with purifying selection at multiple steps during the early phase of viral replication lead to the packaging of largely unmutated genomes, providing a mechanism by which mutant Vif variants can persist in infected individuals. The persistence of genomes containing mutated <it>gag </it>genes despite this selection pressure indicates that dual infection and complementation can result in the packaging of hypermutated genomes which, through recombination with wild-type genomes, could increase viral genetic variation and contribute to evolution.</p

A Nodal Signaling Pathway Regulates the Laterality of Neuroanatomical Asymmetries in the Zebrafish Forebrain

AbstractAnimals show behavioral asymmetries that are mediated by differences between the left and right sides of the brain. We report that the laterality of asymmetric development of the diencephalic habenular nuclei and the photoreceptive pineal complex is regulated by the Nodal signaling pathway and by midline tissue. Analysis of zebrafish embryos with compromised Nodal signaling reveals an early role for this pathway in the repression of asymmetrically expressed genes in the diencephalon. Later signaling mediated by the EGF-CFC protein One-eyed pinhead and the forkhead transcription factor Schmalspur is required to overcome this repression. When expression of Nodal pathway genes is either absent or symmetrical, neuroanatomical asymmetries are still established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determine the laterality of the asymmetry

Reported Changes in Dietary Behavior Following a First Clinical Diagnosis of Central Nervous System Demyelination

Background/objectives: Although the current evidence is insufficient to recommend a special diet for people with multiple sclerosis (MS), dietary advice for people with MS is prolific online and in the media. This study aimed to describe dietary changes made in the year following a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. Subjects/methods: We used follow-up data from the Ausimmune Study, a multicentre matched case-control study examining the environmental risk factors for a FCD. A total of 244 cases (60 male, 184 female) completed a 1-year follow-up interview, which included a question about dietary changes. We described the number and proportion (%) of participants who reported making dietary changes and the type of change made. We investigated independent predictors of making a dietary change using a multivariable logistic regression model. Results: A total of 38% (n = 92) of participants at the 1-year follow-up reported making at least one dietary change over the last year. There were no statistically significant independent associations between any participant characteristic and odds of making a dietary change. Of those who made at least one dietary change, the most common changes were increasing fruit and/or vegetable intake (27%, n = 25) and following a low-fat diet (25%, n = 23). Conclusion: A considerable proportion of the study population reported making at least one dietary change in the year following a FCD, with the majority of changes being toward a healthier diet. Further research is warranted to investigate the reasons behind any dietary changes adopted by people with a FCD or with MS, and whether making a dietary change has benefits for the progression of demyelinating diseases, e.g., to a diagnosis of MS, as well as for general health and well-being.Funding for the Ausimmune Study was provided by the National Multiple Sclerosis Society of the United States of America (NMSS RG 3364A1/2), the National Health and Medical Research Council of Australia (313901) and Multiple Sclerosis Research Australia. LB is funded by a MSWA Postdoctoral Research Fellowship. RL is funded by a National Health and Medical Research Council of Australia Senior Research Fellowship (1107343)

Aerosol Lidar and MODIS Satellite Comparisons for Future Aerosol Loading Forecast

Knowledge of the concentration and distribution of atmospheric aerosols using both airborne lidar and satellite instruments is a field of active research. An aircraft based aerosol lidar has been used to study the distribution of atmospheric aerosols in the California Central Valley and eastern US coast. Concurrently, satellite aerosol retrievals, from the MODIS (Moderate Resolution Imaging Spectroradiometer) instrument aboard the Terra and Aqua satellites, were take over the Central Valley. The MODIS Level 2 aerosol data product provides retrieved ambient aerosol optical properties (e.g., optical depth (AOD) and size distribution) globally over ocean and land at a spatial resolution of 10 km. The Central Valley topography was overlaid with MODIS AOD (5x5 sq km resolution) and the aerosol scattering vertical profiles from a lidar flight. Backward air parcel trajectories for the lidar data show that air from the Pacific and northern part of the Central Valley converge confining the aerosols to the lower valley region and below the mixed layer. Below an altitude of 1 km, the lidar aerosol and MODIS AOD exhibit good agreement. Both data sets indicate a high presence of aerosols near Bakersfield and the Tehachapi Mountains. These and other results to be presented indicate that the majority of the aerosols are below the mixed layer such that the MODIS AOD should correspond well with surface measurements. Lidar measurements will help interpret satellite AOD retrievals so that one day they can be used on a routine basis for prediction of boundary layer aerosol pollution events

Human Skin, Oral, and Gut Microbiomes Predict Chronological Age.

Human gut microbiomes are known to change with age, yet the relative value of human microbiomes across the body as predictors of age, and prediction robustness across populations is unknown. In this study, we tested the ability of the oral, gut, and skin (hand and forehead) microbiomes to predict age in adults using random forest regression on data combined from multiple publicly available studies, evaluating the models in each cohort individually. Intriguingly, the skin microbiome provides the best prediction of age (mean ± standard deviation, 3.8 ± 0.45 years, versus 4.5 ± 0.14 years for the oral microbiome and 11.5 ± 0.12 years for the gut microbiome). This also agrees with forensic studies showing that the skin microbiome predicts postmortem interval better than microbiomes from other body sites. Age prediction models constructed from the hand microbiome generalized to the forehead and vice versa, across cohorts, and results from the gut microbiome generalized across multiple cohorts (United States, United Kingdom, and China). Interestingly, taxa enriched in young individuals (18 to 30 years) tend to be more abundant and more prevalent than taxa enriched in elderly individuals (&gt;60 yrs), suggesting a model in which physiological aging occurs concomitantly with the loss of key taxa over a lifetime, enabling potential microbiome-targeted therapeutic strategies to prevent aging.IMPORTANCE Considerable evidence suggests that the gut microbiome changes with age or even accelerates aging in adults. Whether the age-related changes in the gut microbiome are more or less prominent than those for other body sites and whether predictions can be made about a person's age from a microbiome sample remain unknown. We therefore combined several large studies from different countries to determine which body site's microbiome could most accurately predict age. We found that the skin was the best, on average yielding predictions within 4 years of chronological age. This study sets the stage for future research on the role of the microbiome in accelerating or decelerating the aging process and in the susceptibility for age-related diseases

Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling.

(i) NR supplementation protocol (NCT02812238) and (ii) healthy volunteer blood were obtained from the NIH Clinical Center Blood Bank. We thank and acknowledge the assistance of Dan Yan and Natalia Dmitrieva from Manfred Boehm’s group (NHLBI) for the IncuCyte live-cell analysis. We also thank Yun-Wei A. Hsu for her support with the metabolomics analysis at the Northwest Metabolomics Research Center (NIH grant 1S10OD021562-01).Peer reviewe

Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs

The extracellular lysophospholipase D autotaxin (ATX) and its product, lysophosphatidic acid, have diverse functions in development and cancer, but little is known about their functions in the immune system. Here we found that ATX had high expression in the high endothelial venules of lymphoid organs and was secreted. Chemokine-activated lymphocytes expressed receptors with enhanced affinity for ATX, which provides a mechanism for targeting the secreted ATX to lymphocytes undergoing recruitment. Lysophosphatidic acid induced chemokinesis in T cells. Intravenous injection of enzymatically inactive ATX attenuated the homing of T cells to lymphoid tissues, probably through competition with endogenous ATX and exertion of a dominant negative effect. Our results support the idea of a new and general step in the homing cascade in which the ectoenzyme ATX facilitates the entry of lymphocytes into lymphoid organs