A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Widespread signatures of positive selection for cGAS and OAS1 across the primate lineage.

<p>Phylogenetic analyses of cGAS <b>(A,B)</b> and OAS1 <b>(C,D)</b> were carried out using sequences from 22 matching primate species. <b>(A)</b> A species tree displaying sampled primate sequences for cGAS with dN/dS (ω) values obtained from free-ratio analyses (PAML[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref045" target="_blank">45</a>], see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#sec013" target="_blank">Methods</a>) indicated above each branch. ω values > 1 or at least 3 nonsynonymous: 0 synonymous amino acid changes are labeled in red with the corresponding branch (red branch). <b>(B)</b> cGAS gene structure with annotated domains and catalytic residues (below). Amino acid sites with statistically significant ω values obtained from NSsites (PAML [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref044" target="_blank">44</a>]), FUBAR, and MEME (HyPhy [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref046" target="_blank">46</a>]) are indicated above the gene. <b>(C)</b> ω values for OAS1 across primate evolution. The species tree is labeled as described for the cGAS tree. <b>(D)</b> OAS1 gene structure with amino acids displaying statistical significant ω values. Actual amino acid residue refers to human reference sequence. Catalytic amino acid residues for both cGAS and OAS1 are indicated within the gene diagram.</p

Proposed models for shared and distinct modes of adaptation for cGAS and OAS proteins in primates.

<p>An ancestral protein (red) with template independent polymerase activity was challenged by pathogens (green), which led to gene duplications and divergence resulting in ancestral cGAS (blue) and ancestral OAS (yellow). cGAS and OAS likely faced shared and distinct inhibitors encoded by pathogens (colored hexagons). Extensive positive selection of cGAS and OAS resulted in a variety of substitutions that evade inhibition by pathogens. For cGAS, sampling of amino acid substitutions on protein surfaces (gray stars) and the expression of spliceforms that may produce molecular mimics or cGAS variant proteins that evade antagonism could provide diverse mechanisms of escape from pathogen-encoded inhibitors. Some OAS genes also fix amino acid substitutions (gray stars) and may also evade pathogens via duplications and gene fusion events evident in OAS2 and OAS3.</p

Evolutionary histories vary across the OAS gene family in primates.

<p>Phylogenetic analyses of OAS1, OAS2, OAS3, and OASL were carried out using sequences from 11 matching primate species. <b>(A)</b> Gene structures of the OAS gene family members in primates. NTase (red) and OAS1-C (gray) domains are indicated. For OASL the ubiquitin-like domains (yellow) are also indicated. Amino acid sites with statistically significant ω values obtained from NSsites (PAML [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref044" target="_blank">44</a>]), FUBAR, and MEME (HyPhy [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref045" target="_blank">45</a>]) are indicated above the gene. <b>(B)</b> Primate species trees with ω values obtained from free-ratio analyses in PAML [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005203#pgen.1005203.ref044" target="_blank">44</a>] for each lineage. dN/dS values and lineages with ω > 1 or at least 3 nonsynonymous:0 synonymous amino acid substitutions are highlighted in red.</p

cGAS and OAS1 act in parallel innate defense signaling pathways.

<p><b>(A)</b> Model of cGAS signaling. Upon detection and binding of cytoplasmic DNA from viruses (green), cGAS (blue) dimerizes and generates cGAMP, which in turn activates STING signaling (TBK1-IRF3) to promote transcription of interferon beta. <b>(B)</b> Model of OAS signaling. Upon detection and binding of double-stranded RNA in the cytoplasm from viruses (green), OAS synthesizes 2–5 oligoadenylate, which activates RNase L and leads to the destruction of viral and cellular RNAs.</p

Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films

The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.D.R. acknowledges the fellowship funded by the Autonomic Community of Madrid (CAM). J.T, M.C, J.M and D.R acknowledge financial support by Spanish Ministry of Science (MEC) under grant No. TEC2006-10316 and CAM under grant No. 200550M056. C.B. acknowledges funding provided by MEC under grant No. BIO2007-67523. Work at Centro de Astrobiología was supported by European Union (EU), Instituto Nacional de Técnica Aeroespacial (INTA), MEC and CAM. All the authors acknowledge A. Cebollada, J.M. García-Martín, J. García, J.L. Costa-Kramer, M. Arroyo-Hernández and J.V. Anguita for their assistance in the gold deposition on the cantilevers.Peer reviewe