Chronic viral disease constitutes a major global health problem, with several hundred million people affected and an associated elevated number of deaths. An increasing number of disorders caused by ...human flaviviruses are related to their capacity to establish a persistent infection. Here we show that Usutu virus (USUV), an emerging zoonotic flavivirus linked to sporadic neurologic disease in humans, can establish a persistent infection in cell culture. Two independent lineages of Vero cells surviving USUV lytic infection were cultured over 82 days (41 cell transfers) without any apparent cytopathology crisis associated. We found elevated titers in the supernatant of these cells, with modest fluctuations during passages but no overall tendency towards increased or decreased infectivity. In addition to full-length genomes, viral RNA isolated from these cells at passage 40 revealed the presence of defective genomes, containing different deletions at the 5' end. These truncated transcripts were all predicted to encode shorter polyprotein products lacking membrane and envelope structural proteins, and most of non-structural protein 1. Treatment with different broad-range antiviral nucleosides revealed that USUV is sensitive to these compounds in the context of a persistent infection, in agreement with previous observations during lytic infections. The exposure of infected cells to prolonged treatment (10 days) with favipiravir and/or ribavirin resulted in the complete clearance of infectivity in the cellular supernatants (decrease of ~5 log
in virus titers and RNA levels), although modest changes in intracellular viral RNA levels were recorded (<2 log
decrease). Drug withdrawal after treatment day 10 resulted in a relapse in virus titers. These results encourage the use of persistently-infected cultures as a surrogate system in the identification of improved antivirals against flaviviral chronic disease.
This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR)
clinical isolates obtained from a 2015 ...Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (
= 101) of the XDR isolates, distantly followed by ST244 (
= 16), ST253 (
= 12), ST235 (
= 8), and ST111 (
= 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (
= 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of
mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
Aims
To identify and synthesize evidence on the use of action research methods in mental health nursing care.
Design
Systematic review.
Data Sources
CINAHL, Web of Science, PubMed and Scopus ...databases were searched in January 2021.
Review Methods
Data were selected using the updated Preferred Reporting Items for Systematic Reviews and Meta‐Analysis framework. Two reviewers independently conducted the study selection, and quality appraisal using Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, data extraction and data analysis procedures.
Results
Sixteen studies, half of which used participatory action research, were included in this review. Nurses, along with other stakeholders, were an active part of the action research process. The main topics of interest addressed were categorized as improving the adoption of a person‐centred approach to care and improving decision‐making procedures. The use of action research helped the participants to identify the meaning they attached to the topic of interest to be improved. Moreover, this method helped to identify needs and strategies for improving care. The studies concurred that the use of action research enabled participants to gain awareness, improve attitudes and acquire knowledge. In addition, it enabled participants to gain confidence and security in the group context, as key aspects of their empowerment.
Conclusion
This review shows the usefulness of action research in any mental health nursing context, contributing to the improvement of care at both the individual and collective levels.
Impact
This paper demonstrates the use of the action research method in the field of mental health nursing. Its use has improved the clinical practice of nurses as well as that of teams in both community and hospital settings, addressing issues of the person‐centred approach to care and decision‐making procedures.
Pepino mosaic virus (PepMV) (family Alphaflexiviridae, genus Potexvirus) is a mechanically transmitted tomato pathogen that, over the last decade, has evolved from emerging to endemic worldwide. ...Here, two heat-shock cognate (Hsc70) isoforms were identified as part of the coat protein (CP)/Hsc70 complex in vivo, following full-length PepMV and CP agroinoculation. PepMV accumulation was severely reduced in Hsp70 virus-induced gene silenced and in quercetin-treated Nicotiana benthamiana plants. Similarly, in vitro-transcribed as well as virion RNA input levels were reduced in quercetin-treated protoplasts, suggesting an essential role for Hsp70 in PepMV replication. As for Potato virus X, the PepMV CP and triple gene-block protein 1 (TGBp1) self-associate and interact with each other in vitro but, unlike in the prototype, both PepMV proteins represent suppressors of transgene-induced RNA silencing with different modes of action; CP is a more efficient suppressor of RNA silencing, sequesters the silencing signal by preventing its spread to neighboring cells and its systemic movement. Here, we provide evidence for additional roles of the PepMV CP and host-encoded Hsp70 in viral infection, the first as a truly multifunctional protein able to specifically bind to a host chaperone and to counterattack an RNA-based defense mechanism, and the latter as an essential factor for PepMV infection.
We have recently shown that α-C-galactosylceramide (α-C-GalCer) stimulates invariant natural killer T (iNKT) cells and preferentially induces a T helper 1 (Th1)-type response in mice. However, ...α-C-GalCer was found to be a rather weak ligand against human iNKT cells in vitro. Therefore, in this study, we sought to identify a compound that displays a strong stimulatory activity against human iNKT cells, by determining the biological activities of several C-glycoside analogues. From the in vitro screening assays, we found that almost all C-glycoside analogues, which have an E-alkene linker between sugar and lipid moieties, are able to activate human iNKT cells and to induce the maturation and activation of human dendritic cells through iNKT-cell activation. In summary, although α-galactosylceramide (α-GalCer) remains the strongest iNKT-cell ligand, our study identified E-alkene-linked C-glycoside analogues as potent human iNKT-cell stimulants, and indicated that these analogues could be used as a therapeutic agent in the future for diseases resolved by Th1-type responses.
Few cases have been reported to date, in which a massive rhabdomyolysis causes a cardiac arrest in a male adult suffering from undiagnosed McArdle disease. Veno‐arterial extracorporeal membrane ...oxygenation and cytokine adsorption filter (CytoSorb®) were required to reach a complete and successful recovery.
The high failure rate of innovation projects motivates us to understand the perceptions about resistances and barriers of the main stakeholders to improving success rates.
This study aims to analyze ...the readiness for change in the implementation of a 3D printing project in a Catalan tertiary hospital prior to its implementation.
We used a web-based, voluntary, and anonymous survey using the Normalization Measurement Development questionnaire (NoMAD) to gather views and perceptions from a selected group of health care professionals at Germans Trias i Pujol University Hospital.
In this study, 58 professionals, including heads of service (n=30, 51%), doctors (n=18, 31%), nurses (n=7, 12%), and support staff (n=3, 5%), responded to the questionnaire. All groups saw the value of the project and were willing to enroll and support it. Respondents reported the highest scores (out of 5) in cognitive participation (mean 4.45, SD 0.04), coherence (mean 3.72, SD 0.13), and reflective monitoring (mean 3.80, SD 0.25). The weakest score was in collective action (mean 3.52, SD 0.12). There were no statistically significant differences in scores among professions in the survey.
The 3D printing project implementation should pay attention to preparing, defining, sharing, and supporting the operational work involved in its use and implementation. It should also understand, assess, and communicate the ways in which the new set of practices can affect the users and others around them. We suggest that health officers and politicians consider this experience as a solid ground toward the development of a more efficient health innovation system and as a catalyst for transformation.
Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This ...study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically ...excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (
< 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the
(
/
) gene, rs35286811, emerged as significantly associated with CVA symptomatology (
= 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (
< 0.0001), and significantly higher in carriers of the rs35286811 risk allele (
< 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (
< 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces
as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.
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