Increasing anti-S antibody testing: a quality improvement initiative with evolving COVID-19 guidelines.

BackgroundCOVID-19 management guidelines are constantly evolving, making them difficult to implement practically. Ronapreve was a neutralising monoclonal antibody introduced into UK COVID-19 guidelines in 2021. It reduces mortality in seronegative patients infected with non-omicron variants. Antibody testing on admission is therefore vital in ensuring patients could be considered for Ronapreve as inpatients.Local problemWe found that on our COVID-19 ward, 31.4% of patients were not having anti-S tests despite fulfilling the other criteria to be eligible for Ronapreve. This was identified as an important target to improve; by not requesting anti-S tests, we were forgoing the opportunity to use an intervention that could improve outcomes.MethodsWe analysed patient records for patients with COVID-19 admitted to our ward over 4 months to observe if awareness of the need to request anti-S increased through conducting plan-do-study-act (PDSA) cycles.InterventionsOur first intervention was an multidisciplinary team (MDT) discussion at our departmental audit meeting highlighting our baseline findings and the importance of anti-S requesting. Our second intervention was to hang printed posters in both the doctors' room and the ward as a visual reminder to staff. Our final intervention was trust-wide communications of updated local COVID-19 guidance that included instructions for anti-S requesting on admission.ResultsOur baseline data showed that only 68.6% of patients with symptomatic COVID-19 were having anti-S antibody tests requested. This increased to 95.0% following our three interventions. There was also a reduction in the amount of anti-S requests being 'added on', from 57.1% to 15.8%.ConclusionsCOVID-19 guidelines are constantly evolving and require interventions that can be quickly and easily implemented to improve adherence. Sustained reminders through different approaches allowed a continued increase in requesting. This agrees with research that suggests a mixture of educational sessions and visual reminders of guidelines increase their application in clinical practice

Non-consensual sharing of private sexually explicit media amongst university students

This research was the first in the U.K. to examine the prevalence and nature of non-consensual sharing of sexually explicit messages, pictures, and videos and to examine if this varies according to gender and by role (i.e. perpetrator, victim or as dual role of perpetrator/victim). In a sample of 391 young adults (aged 18-25 years) questionnaire data on subjective norms, consensual and non-consensual sharing, and their motivations for these behaviors were collected. Perpetration of and victimization through non-consensual sharing was experienced by a substantial number of individuals. There was an association between reporting perpetration of non-consensual sharing and experiencing victimization. An association was also found between reporting being pressured (i.e., coerced) to send sexually explicit material and experiencing victimization of non-consensual sharing, which suggests that these behaviours may form part of a continuum of violence and abuse, potentially within intimate relationships. No association was found between gender and (i) perpetration or (ii) victimization. However, from a gendered perspective, females perceived there was greater social pressure to post messages, pictures and videos, compared with males. Motivations for non-consensual sharing were commonly explained as for fun/a joke, and generally not thought of as problematic, although some victims perceived motivations to be more negative and/or related to revenge/causing distress. Given that this research examined non-consensual sharing across messages, pictures and videos for both victimization and perpetration and found it was both perpetrated and experienced by females and males, this does not support the common perception that this is a male perpetrated behaviour against women. This has implications for education, policy, intervention and prevention, with approaches needing to be inclusive of both males and females when addressing perpetration and victimization

A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere

<div><p>Transcriptional inactivation of the budding yeast centromere has been a widely used tool in studies of chromosome segregation and aneuploidy. In haploid cells when an essential chromosome contains a single conditionally inactivated centromere (<i>GAL-CEN</i>), cell growth rate is slowed and segregation fidelity is reduced; but colony formation is nearly 100%. Pedigree analysis revealed that only 30% of the time both mother and daughter cell inherit the <i>GAL-CEN</i> chromosome. The reduced segregation capacity of the <i>GAL-CEN</i> chromosome is further compromised upon reduction of pericentric cohesin (<i>mcm21∆</i>), as reflected in a further diminishment of the Mif2 kinetochore protein at <i>GAL-CEN</i>. By redistributing cohesin from the nucleolus to the pericentromere (by deleting <i>SIR2</i>), there is increased presence of the kinetochore protein Mif2 at <i>GAL-CEN</i> and restoration of cell viability. These studies identify the ability of cohesin to promote chromosome segregation via kinetochore assembly, in a situation where the centromere has been severely compromised.</p></div

Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels

<div><p>Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of <i>Aedes aegypti</i> (<i>Ae</i>Kir1). Injection of VU573 into the hemolymph of adult female mosquitoes (<i>Ae. aegypti</i>) disrupts the production and excretion of urine in a manner consistent with channel block of <i>Ae</i>Kir1 and renders the mosquitoes incapacitated (flightless or dead) within 24 hours. Moreover, the toxicity of VU573 in mosquitoes (<i>Ae. aegypti</i>) is exacerbated when hemolymph potassium levels are elevated, suggesting that Kir channels are essential for maintenance of whole-animal potassium homeostasis. Our study demonstrates that renal failure is a promising mechanism of action for killing mosquitoes, and motivates the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides.</p></div

Pedigree analysis of <i>mcm21Δ</i>.

<p>G1 cells (<i>mcm21</i>Δ <i>GAL-CEN3</i>) were micromanipulated on YEP-galactose plates and after the first division mothers and daughters were separated and allowed to grow approximately 24 h. Images of microcolonies were photographed. A. Both mother and daughter cells divided multiple times. B. Only mother cells divided multiple times. C. Only mother cell divided and grew into an observable colony. D. Neither mother nor daughter progressed beyond 2–3 divisions.</p

Cohesin concentration in the pericentric region in <i>GAL-CEN3</i>, <i>mcm21Δ</i> and <i>mcm21Δ</i>, <i>sir2Δ</i> mutants.

<p>A. Cells containing <i>GAL-CEN3</i> as the only centromere in chromosome 3 were transferred from lactose to galactose and grown on galactose for over 6 hours to inactivate the centromere. Chromatin immunoprecipitation was performed as described in Snider et al., (2014) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006021#pgen.1006021.ref027" target="_blank">27</a>], using a ChIP grade antibody against GFP to immunoprecipitate the only copy of Smc3 fused to GFP at the C-terminus of Smc3 in the genome. Oligonucleotide primers against <i>CEN3</i> (114,800), 8 kb (Stp22, position 105696..106853), 10 kb (Ilv6, position 104619..105548) and 87 kb (kar4 27929..28936) were utilized. Primers were designed to amplify a 600 bp fragment for each of the 4 reactions. Titrations of template were performed to ensure the analysis was in the linear range of amplification. For <i>GAL-CEN3</i> glucose, the integrated intensity ranged from 5.5 x 10^6 to 6.1 x 10^6 (indicated by glucose text inset in graph)(n = 4). The average was 5.78 x 10^6 ± 2.5 x 10^5 (STD). For GAL-CEN3 galactose, integrated intensity ranged from 1.2 x 10^6 to 3.3 x 10^6 (indicated by galactose text inset in graph)(n = 4). The average was 2.33 x 10^6 ± 8.3 x 10^5 (STD). For <i>STP22</i> (8 kb), <i>ILV6</i> (10 kb) and <i>KAR4</i> (87 kb) the galactose and glucose products ranged from 2.4 x 10^5 to 5.6 x 10^5 (n = 3). There was no significant difference between glucose and galactose grown samples for the 8, 10 or 87 kb products. B. The concentration of Smc3-GFP was determined in <i>GAL-CEN3</i> WT, <i>mcm21</i>∆ and <i>mcm21</i>∆ <i>sir2</i>∆ mutants. The concentration of pericentric cohesin is reduced in <i>mcm21</i>∆ cells (from 30,540 to 18,509 arbitrary fluorescence units). In the double mutant, <i>mcm21</i>∆ <i>sir2</i>∆, the concentration of cohesin in the pericentromere is increased to almost wild-type levels (29,848 vs 30,540). C. Representative images of Smc3-GFP in <i>GAL-CEN3</i> WT (left), <i>mcm21</i>∆ (middle) and <i>mcm21</i>∆ <i>sir2</i>∆ (right). Spindle poles are visualized using Spc29-RFP, cohesin with Smc3-GFP. The rightmost image in each strain is an overlay of the spindle poles with Smc3-GFP. White arrows indicate the cohesin barrel concentrated in the pericentric chromatin between the spindle poles (red). Note the absence of the cohesin barrel in <i>mcm21Δ</i>.</p