Respiratory syncytial virus outbreak in a long-term care facility detected using reverse transcriptase polymerase chain reaction: an argument for real-time detection methods.

ObjectivesTo report an outbreak of respiratory synctyial virus (RSV) in a long-term care facility (LTCF) during ongoing routine respiratory illness surveillance.DesignRapid antigen testing, viral culture, direct fluorescent antibody (DFA) testing, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for up to 15 viruses in symptomatic residents and chart review.SettingA 120-bed LTCF.MeasurementsComparison of rapid antigen testing, respiratory viral cultures, and DFA testing and RT-PCR in residents with symptoms of a respiratory tract infection.ResultsTwenty-two of 52 residents developed symptoms of a respiratory tract infection between January 29, 2008, and February 26, 2008. RSV was detected using RT-PCR in seven (32%) of the 22 cases. None of the seven cases had positive RSV rapid antigen testing, and only two had positive culture or DFA results. This outbreak occurred during a time when state wide RSV rates were rapidly declining. One patient was admitted to the hospital during the infection and subsequently died.ConclusionRSV may cause outbreaks in LTCFs that traditional diagnostic methods do not detect. RT-PCR can provide a more timely and accurate diagnosis of outbreaks, which allows for early symptomatic treatment, rational use of antibiotics, and improved infection control

Nutrigenomic profiling of transcriptional processes affected in liver and distal intestine in response to a soybean meal-induced nutritional stress in Atlantic salmon (Salmo salar)

The aim of the present study was to generate an experimental model to characterize the nutrigenomic profile of a plant-derived nutritional stress. Atlantic salmon (Salmo salar) was used as the model species and the nutritional stress was induced by inclusion of dietary defatted soybean meal (SBM), as this ingredient had been previously demonstrated to induce enteropathy in the distal intestine and reduced growth performance in salmon. Triplicate groups of Atlantic salmon were fed increasing concentrations (0, 100, 200 and 300 g kg-1) of SBM for 12 weeks and reduced growth performance was used as the indicator of nutritional stress. The transcriptome was analysed in two tissues, distal intestine and liver, with the hypothesis being that intestinal gene expression would be dominated by specific responses to SBM whereas the liver transcriptome would include gene expression responses that could be more general and related to overall performance. Specifically, a set of 133 genes was differentially expressed in liver including 45 genes in common with the intestinal response. The liver specific response included genes involved in protein digestion and energy metabolism that were up-regulated, whereas genes in other pathways were generally anabolic and down-regulated. These responses may be more related to general nutritional stress than to SBM per se. This study provides a comprehensive report on the profiles of distal intestine and liver transcriptomes, highlighting the role of the latter tissue in fish undergoing SBM-induced nutritional stress

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest

Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar)

<p>Abstract</p> <p>Background</p> <p>There is an increasing drive to replace fish oil (FO) in finfish aquaculture diets with vegetable oils (VO), driven by the short supply of FO derived from wild fish stocks. However, little is known of the consequences for fish health after such substitution. The effect of dietary VO on hepatic gene expression, lipid composition and growth was determined in Atlantic salmon (<it>Salmo salar</it>), using a combination of cDNA microarray, lipid, and biochemical analysis. FO was replaced with VO, added to diets as rapeseed (RO), soybean (SO) or linseed (LO) oils.</p> <p>Results</p> <p>Dietary VO had no major effect on growth of the fish, but increased the whole fish protein contents and tended to decrease whole fish lipid content, thus increasing the protein:lipid ratio. Expression levels of genes of the highly unsaturated fatty acid (HUFA) and cholesterol biosynthetic pathways were increased in all vegetable oil diets as was SREBP2, a master transcriptional regulator of these pathways. Other genes whose expression was increased by feeding VO included those of NADPH generation, lipid transport, peroxisomal fatty acid oxidation, a marker of intracellular lipid accumulation, and protein and RNA processing. Consistent with these results, HUFA biosynthesis, hepatic β-oxidation activity and enzymic NADPH production were changed by VO, and there was a trend for increased hepatic lipid in LO and SO diets. Tissue cholesterol levels in VO fed fish were the same as animals fed FO, whereas fatty acid composition of the tissues largely reflected those of the diets and was marked by enrichment of 18 carbon fatty acids and reductions in 20 and 22 carbon HUFA.</p> <p>Conclusion</p> <p>This combined gene expression, compositional and metabolic study demonstrates that major lipid metabolic effects occur after replacing FO with VO in salmon diets. These effects are most likely mediated by SREBP2, which responds to reductions in dietary cholesterol. These changes are sufficient to maintain whole body cholesterol levels but not HUFA levels.</p

Microbial biogeography of the wombat gastrointestinal tract

Most herbivorous mammals have symbiotic microbes living in their gastrointestinal tracts that help with harvesting energy from recalcitrant plant fibre. The bulk of research into these microorganisms has focused on samples collected from faeces, representing the distal region of the gastrointestinal (GI) tract. However, the GI tract in herbivorous mammals is typically long and complex, containing different regions with distinct physico-chemical properties that can structure resident microbial communities. Little work has been done to document GI microbial communities of herbivorous animals at these sites. In this study, we use 16S rRNA gene sequencing to characterize the microbial biogeography along the GI tract in two species of wombats. Specifically, we survey the microbes along four major gut regions (stomach, small intestine, proximal colon, distal colon) in a single bare-nosed wombat (Vombatus ursinus) and a single southern hairy-nosed wombat (Lasiorhinus latifrons). Our preliminary results show that GI microbial communities of wombats are structured by GI region. For both wombat individuals, we observed a trend of increasing microbial diversity from stomach to distal colon. The microbial composition in the first proximal colon region was more similar between wombat species than the corresponding distal colon region in the same species. We found several microbial genera that were differentially abundant between the first proximal colon (putative site for primary plant fermentation) and distal colon regions (which resemble faecal samples). Surprisingly, only 10.6% (98) and 18.8% (206) of amplicon sequence variants (ASVs) were shared between the first proximal colon region and the distal colon region for the bare-nosed and southern hairy-nosed wombat, respectively. These results suggest that microbial communities in the first proximal colon region—the putative site of primary plant fermentation in wombats—are distinct from the distal colon, and that faecal samples may have limitations in capturing the diversity of these communities. While faeces are still a valuable and effective means of characterising the distal colon microbiota, future work seeking to better understand how GI microbiota impact the energy economy of wombats (and potentially other hindgut-fermenting mammals) may need to take gut biogeography into account

Ventricular Stimulus Site Influences Dynamic Dispersion of Repolarization In The Intact Human Heart

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apico-basal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base and LVepi base. Overall 725 restitution curves were analyzed, 74% of slopes had an Smax>1 (p < 0.001), mean Smax=1.76. APD was shorter in the LVepi compared to LVendo regardless of pacing site (30ms difference during RVendo pacing, 25ms during LVendo and 48ms during LVepi; 50(th) quantile, p<0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77ms, 50(th) quantile: p<0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63±0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 ±1.9 and -0.71 ±0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI, RT gradients exist which are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be pro-arrhythmic

Ethnopolitics Across Central and Eastern Europe in a State of Flux: Time for Updating and Upgrading?

This chapter illustrates why and how the existing theoretical models in the study of ethnopolitics need to be updated in light of the latest developments and the increasing impact of new catalysts. These are, namely, anti-immigration and the rise of the populist and radical right across Central and Eastern Europe. This chapter hints that the more systematic cooperation between academic experts in nationalism and academic experts in the populist and radical right will enable: (a) the former to assess more accurately the degree to which new variables such as Euroscepticism and anti-immigrant trends can reshape ethnopolitics, both as a living reality and a field of study, across Central and Eastern Europe; (b) the latter to formulate new interpretative models about how (right-wing) populist and Eurosceptic actors embed their agendas inside the pre-existing political cultures of nationalism and particularistic identity and memory politics. This chapter introduces and outlines the ethnosymbolic approach as well as the triadic and quadratic configurations of ethnopolitics. Then, it proceeds into a more empirical assessment of the applicability of these theoretical approaches in a series of case studies during the 1990s, as well as the more recent emergence of new catalysts and the ensuing necessity to update and upgrade the existing theoretical models

Mobile/portable transuranic waste characterization systems at Los Alamos National Laboratory and a model for their use complex-wide

Los Alamos National Laboratory has implemented mobile and portable characterization and repackaging systems to characterize TRU waste in storage for ultimate shipment and disposal at the Waste Isolation Pilot Plant (WIPP) near Carlsbad, NM. These mobile systems are being used to characterize and repackage waste to meet the full requirements of the WIPP Waste Acceptance Criteria (WAC) and the WIPP Characterization Quality Assurance Program Plan (QAPP). Mobile and portable characterization and repackaging systems are being used to supplement the capabilities and throughputs of existing facilities. Utilization of mobile systems is a key factor that is enabling LANL to: (1) reduce its TRU waste work-off schedule from 36 years to 8.5 years; (2) eliminate the need to construct a $70M+ TRU waste characterization facility; (3) have waste certified for shipment to WIPP when WIPP opens; (4) continue to ship TRU waste to WIPP at the rate of 5000 drums per year; and, (5) reduce overall costs by more than$200M. Aggressive implementation of mobile and portable systems throughout the DOE complex through a centralized-distributed services model will result in similar advantages complex-wide

Mobile/portable transuranic waste characterization systems at Los Alamos National Laboratory and a model for their use complex-wide

Los Alamos National Laboratory (LANL) has implemented mobile and portable characterization and repackaging systems to characterize transuranic (TRU) waste in storage for ultimate shipment and disposal at the Waste Isolation Pilot Plant (WIPP) near Carlsbad, NM. These mobile systems are being used to characterize and repackage waste to meet the full requirements of the WIPP Waste Acceptance Criteria (WAC) and the WIPP Characterization Quality Assurance Program Plan (QAPP). Mobile and portable characterization and repackaging systems are being used to supplement the capabilities and throughputs of existing facilities. Utilization of mobile systems is a key factor that is enabling LANL to (1) reduce its TRU waste work-off schedule from 36 years to 8.5 years; (2) eliminate the need to construct a $70M+ TRU waste characterization facility; (3) have waste certified for shipment to WIPP when WIPP opens; (4) continue to ship TRU waste to WIPP at the rate of 5000 drums per year; and (5) reduce overall costs by more than$200M. Aggressive implementation of mobile and portable systems throughout the Department of Energy complex through a centralized-distributed services model will result in similar advantages complex-wide