Opt-Out Panel Testing for HIV,Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study

Objectives

Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.

Methods

An opt-out ED blood borne virus screening programme was piloted from March 2014 to January 2015. Patients undergoing blood sampling during routine clinical care were offered HIV 1&2 antibody/antigen assay, HBV surface antigen and HCV antibody tests. Linkage to care where necessary was co-ordinated by the study team. New diagnosis and prevalence rates were defined as the new cases per 1000 tested and number of positive tests per 1000 tested respectively.

Results

Over 45 weeks of testing, of 10,000 patient visits, 8,839 individual patient samples were available for analysis following removal of duplicates. A sustained target uptake of >50% was obtained after week 3. 97(1.09%), 44(0.49%) and 447(5.05%) HIV, Hepatitis B and Hepatitis C tests were positive respectively. Of these, 7(0.08%), 20(0.22%) and 58(0.66%) were new diagnoses of HIV, Hepatitis B and Hepatitis C respectively. The new diagnosis rate for HIV, Hepatitis B and Hepatitis C was 0.8, 2.26 and 6.5 per 1000 and study prevalence for HIV, Hepatitis B and Hepatitis C was 11.0, 5.0 and 50.5 per 1000 respectively.

Conclusions

Opt-out blood borne viral screening was feasible and acceptable in an inner-city ED. Blood borne viral infections were prevalent in this population and newly diagnosed cases were diagnosed and linked to care. These results suggest widespread blood borne viral testing in differing clinical locations with differing population demographic risks may be warranted.     

Has gene duplication impacted the evolution of Eutherian longevity?

One of the greatest unresolved questions in aging biology is determining the genetic basis of interspecies longevity variation. Gene duplication is often the key to understanding the origin and evolution of important Eutherian phenotypes. We systematically identified longevity‐associated genes in model organisms that duplicated throughout Eutherian evolution. Longevity‐associated gene families have a marginally significantly higher rate of duplication compared to non‐longevity‐associated gene families. Anti‐longevity‐associated gene families have significantly increased rate of duplication compared to pro‐longevity gene families and are enriched in neurodegenerative disease categories. Conversely, duplicated pro‐longevity‐associated gene families are enriched in cell cycle genes. There is a cluster of longevity‐associated gene families that expanded solely in long‐lived species that is significantly enriched in pathways relating to 3‐UTR‐mediated translational regulation, metabolism of proteins and gene expression, pathways that have the potential to affect longevity. The identification of a gene cluster that duplicated solely in long‐lived species involved in such fundamental processes provides a promising avenue for further exploration of Eutherian longevity evolution.     

A multi‐resolution model to capture both global fluctuations of an enzyme and molecular recognition in the ligand‐binding site

In multi‐resolution simulations, different system components are simultaneously modeled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is needed in the active site to capture the chemistry of ligand binding. Global properties of the rest of the protein also play an essential role, determining the structure and fluctuations of the binding site; however, these can be modeled on a coarser level. Similarly, in the most computationally efficient scheme only the solvent hydrating the active site requires atomistic detail. We present a methodology to couple atomistic and coarse‐grained protein models, while solvating the atomistic part of the protein in atomistic water. This allows a free choice of which protein and solvent degrees of freedom to include atomistically. This multi‐resolution methodology can successfully model stable ligand binding, and we further confirm its validity by exploring the reproduction of system properties relevant to enzymatic function. In addition to a computational speedup, such an approach can allow the identification of the essential degrees of freedom playing a role in a given process, potentially yielding new insights into biomolecular function. Proteins 2016; 84:1902–1913. © 2016 Wiley Periodicals, Inc.     

Genomic features in the breakpoint regions between syntenic blocks

MOTIVATION: We study the largely unaligned regions between the syntenic blocks conserved in humans and mice, based on data extracted from the UCSC genome browser. These regions contain evolutionary breakpoints caused by inversion, translocation and other processes. RESULTS: We suggest explanations for the limited amount of genomic alignment in the neighbourhoods of breakpoints. We discount inferences of extensive breakpoint reuse as artefacts introduced during the reconstruction of syntenic blocks. We find that the number, size and distribution of small aligned fragments in the breakpoint regions depend on the origin of the neighbouring blocks and the other blocks on the same chromosome. We account for this and for the generalized loss of alignment in the regions partially by artefacts due to alignment protocols and partially by mutational processes operative only after the rearrangement event. These results are consistent with breakpoints occurring randomly over virtually the entire genome.     

Maxi K+ channel mediates regulatory volume decrease response in a human bronchial epithelial cell line

The cell regulatory volume decrease (RVD) response triggered by hypotonic solutions is mainly achieved by the coordinated activity of Cl- and K+ channels. We now describe the molecular nature of the K(+) channels involved in the RVD response of the human bronchial epithelial (HBE) cell line 16HBE14o-. These cells, under isotonic conditions, present a K+ current consistent with the activity of maxi K+ channels, confirmed by RT-PCR and Western blot. Single-channel and whole cell maxi K+ currents were readily and reversibly activated following the exposure of HBE cells to a 28% hypotonic solution. Both maxi K+ current activation and RVD response showed calcium dependency, inhibition by TEA, Ba2+, iberiotoxin, and the cationic channel blocker Gd3+ but were insensitive to clofilium, clotrimazole, and apamin. The presence of the recently cloned swelling-activated, Gd3+-sensitive cation channels (TRPV4, also known as OTRPC4, TRP12, or VR-OAC) was detected by RT-PCR in HBE cells. This channel, TRPV4, which senses changes in volume, might provide the pathway for Ca2+ influx under hypotonic solutions and, consequently, for the activation of maxi K+ channels.     

Detection of Hepatitis E Virus Antibodies in Dogs in the United Kingdom

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic pathogens, with pigs predominantly implicated in disease transmission. The rapid rise in human cases in developed countries over the past decade indicates a change in epidemiology of HEV, and it has been suggested that additional animal species may be involved in transmission of infection. Multiple studies have identified contact with dogs as a risk factor for HEV infection in industrialised nations, and a low seroprevalence to HEV has previously been reported in dogs in low-income countries. In this study we aimed to evaluate the possibility that dogs are susceptible to HEV, and determine the frequency with which this occurs. Serum samples from UK dogs with and without hepatitis were screened for HEV-specific antibodies, and canine liver and stool samples were analysed by qPCR for the presence of HEV RNA. We describe evidence to show HEV infection occurs at low levels in dogs in the UK, but the strain of origin is undetermined. The low seroprevalence level of HEV in dogs implies the risk of zoonotic disease transmission is likely to be limited, but further investigations will be required to determine if HEV-infected dogs can transmit HEV to man.     

A comprehensive aerobiological study of the airborne pollen in the Irish environment

Respiratory allergies triggered by pollen allergens represent a significant health concern to the Irish public. Up to now, Ireland has largely refrained from participating in long-term aerobiological studies. Recently, pollen monitoring has commenced in several sampling locations around Ireland. The first results of the pollen monitoring campaigns for Dublin (urban) and Carlow (rural) concerning the period 2017–2019 and 2018–2019, respectively, are presented herein. Additional unpublished pollen data from 1978–1980 and, 2010–2011 were also incorporated in creating the first pollen calendar for Dublin. During the monitoring period over 60 pollen types were identified with an average Annual Pollen Integral (APIn) of 32,217 Pollen × day/m³ for Dublin and 78,411 Pollen × day/m³ for Carlow. The most prevalent pollen types in Dublin were: Poaceae (32%), Urticaceae (29%), Cupressaceae/Taxaceae (11%), Betula (10%), Quercus (4%), Pinus (3%), Fraxinus (2%), Alnus (2%) and Platanus (1%). The predominant pollen types in Carlow were identified as Poaceae (70%), Urticaceae (12%), Betula (10%), Quercus (2%), Fraxinus (1%) and Pinus (1%). These prevalent pollen types increased in annual pollen concentration in both locations from 2018 to 2019 except for Fraxinus. Although higher pollen concentrations were observed for the Carlow (rural) site a greater variety of pollen types were identified for the Dublin (urban) site. The general annual trend in the pollen season began with the release of tree pollen in early spring, followed by the release of grass and herbaceous pollen which dominated the summer months with the annual pollen season coming to an end in October. This behaviour was illustrated for 21 different pollen types in the Dublin pollen calendar. The correlation between ambient pollen concentration and meteorological parameters was also examined and differed greatly depending on the location and study year. A striking feature was a substantial fraction of the recorded pollen sampled in Dublin did not correlate with the prevailing wind directions. However, using non-parametric wind regression, specific source regions could be determined such as Alnus originating from the Southeast, Betula originating from the East and Poaceae originating from the Southwest.

     

New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation

The origin of novel protein-coding genes de novo was once considered so improbable as to be impossible. In less than a decade, and especially in the last five years, this view has been overturned by extensive evidence from diverse eukaryotic lineages. There is now evidence that this mechanism has contributed a significant number of genes to genomes of organisms as diverse as Saccharomyces, Drosophila, Plasmodium, Arabidopisis and human. From simple beginnings, these genes have in some instances acquired complex structure, regulated expression and important functional roles. New genes are often thought of as dispensable late additions; however, some recent de novo genes in human can play a role in disease. Rather than an extremely rare occurrence, it is now evident that there is a relatively constant trickle of proto-genes released into the testing ground of natural selection. It is currently unknown whether de novo genes arise primarily through an ‘RNA-first’ or ‘ORF-first’ pathway. Either way, evolutionary tinkering with this pool of genetic potential may have been a significant player in the origins of lineage-specific traits and adaptations.