Project description:The exponential increase in the numbers of isolates of Carbapenem-Resistant Enterobacteriaceae (CRE) creates the need for using novel therapeutic approaches to save the lives of patients. Fosfomycin has long been considered a rational option for the treatment of CRE to be used as part of a combined therapy scheme. However, the assessment of fosfomycin susceptibility in the laboratory presents a great challenge due to the discrepancies found between different methodologies. Thus, our goal was to evaluate fosfomycin susceptibility in a group of 150 Enterobacteriaceae bacterial isolates using agar dilution as the gold standard technique to compare the results with those obtained by disk diffusion. We found a fosfomycin susceptibility of 79.3% in general terms. By comparing both methodologies, we reported a categorical agreement of 96% without Very Major Errors (VMEs) or Major Errors (MEs) and 4% of minor Errors (mEs). Our results suggest that fosfomycin could provide a rational alternative treatment for those patients that are infected by a Multidrug-Resistant (MDR) microorganism that is currently untreatable and that the disk diffusion and classical agar dilution techniques are adequate to assess the resistance profile of CRE to fosfomycin.
Project description:ObjectivesTo investigate factors associated with anger or confronting others due to COVID-19.DesignOnline cross-sectional survey.SettingData were collected between 17 and 20 July 2020.ParticipantsA total of 2237 participants living in the UK aged 16-75 years.Main outcome measuresReporting having had arguments, felt angry or fallen out with others because of COVID-19. Reporting having confronted or reported someone to the authorities, or that you had been confronted or reported to the authorities, for not wearing a face covering; not keeping your distance from others or being in too large a group; or alternatively following recommended measures too carefully. We used logistic regression analyses to identify factors associated with anger and confrontation.ResultsMost participants reported having had arguments, feeling angry or fallen out with others because of COVID-19 (56%, n = 1255). Twenty-two percent (n = 500) of participants reported that they had confronted or reported someone. Fourteen percent (n = 304) of participants reported that they had been confronted or reported by someone. Confronting someone, having been confronted and feeling angry or having had arguments were strongly associated with each other. Anger and confrontation were associated with younger age, greater likelihood of experiencing significant financial difficulties due to the pandemic, greater perceived risk of COVID-19 and getting information about COVID-19 from social media.ConclusionsMeasures put in place to prevent the spread of COVID-19 have caused considerable strain. Increased support, clear messaging on the rationale for easing restrictions and combatting misinformation on social media may all help decrease tension.
Project description:The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5'end until an ATG codon with a specific nucleotide (nt) context surrounding it is recognized (Kozak rule). According to this model, ATG codons upstream to the beginning of the ORF should affect translation. We perform for the first time, a genome-wide statistical analysis, uncovering a new, more comprehensive and quantitative, set of initiation rules for improving the cost of translation and its efficiency. Analyzing dozens of eukaryotic genomes, we find that in all frames there is a universal trend of selection for low numbers of ATG codons; specifically, 16-27 codons upstream, but also 5-11 codons downstream of the START ATG, include less ATG codons than expected. We further suggest that there is selection for anti optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and fidelity of translation initiation is encoded in the 5'UTR as required by the scanning model, but also at the beginning of the ORF. The observed nt patterns suggest that in all the analyzed organisms the pre-initiation complex often misses the START ATG of the ORF, and may start translation from an alternative initiation start-site. Thus, to prevent the translation of undesired proteins, there is selection for nucleotide sequences with low affinity to the pre-initiation complex near the beginning of the ORF. With the new suggested rules we were able to obtain a twice higher correlation with ribosomal density and protein levels in comparison to the Kozak rule alone (e.g. for protein levels r=0.7 vs. r=0.31; p<10(-12)).
Project description:Although song development in songbirds has been much studied as an analogue of language development in humans, the development of vocal interaction rules has been relatively neglected in both groups. Duetting avian species provide an ideal model to address the acquisition of interaction rules as duet structure involves time and pattern-specific relationships among the vocalizations from different individuals. In this study, we address the development of the most striking properties of duets: the specific answering rules that individuals use to link their own phrase types to those of their partners (duet codes) and precise temporal coordination. By performing two removal experiments in canebrake wrens (Cantorchilus zeledoni), we show that individuals use a fixed phrase repertoire to create new phrase pairings when they acquire a new partner. Furthermore, immediately after pairing, individuals perform duets with poor coordination and poor duet code adherence, but both aspects improve with time. These results indicate that individuals need a learning period to be able to perform well-coordinated duets that follow a consistent duet code. We conclude that both duet coordination and duet code adherence are honest indicators of pair-bond duration.
Project description:Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically.
Project description:Differences in emotion experience and emotion expression between patients with schizophrenia and the healthy population have long been the focus of research and clinical attention. However, few empirical studies have addressed this topic using art-making as a tool of emotion expression. This study explores the differences in brain mechanism during the process of expressing anger between patients with schizophrenia and healthy participants using pictographic psychological techniques. We used functional near-infrared spectroscopy to fully detect changes in frontal cortex activity among participants in two groups-schizophrenia and healthy-during the process of experiencing and expressing anger. The results showed that there were no differences in the experience of anger between the two groups. In the process of anger expression, the dorsolateral prefrontal cortex, frontal pole, and other regions showed significant negative activation among patients with schizophrenia, which was significantly different from that of the healthy group. There were significant differences between patients with schizophrenia and the healthy group in the drawing features, drawing contents, and the ability to describe the contents of their drawings. Moreover, the effect size of the latter was greater than those of the former two. In terms of emotion expression, the drawing data and brain activation data were significantly correlated in each group; however, the correlation patterns differed between groups.
Project description:Everyday beliefs often organize and guide motivations, goals, and behaviors, and, as such, may also differentially motivate individuals to value and attend to emotion-related cues of others. In this way, the beliefs that individuals hold may affect the socioemotional skills that they develop. To test the role of emotion-related beliefs specific to anger, we examined an educational context in which beliefs could vary and have implications for individuals' skill. Specifically, we studied 43 teachers' beliefs about students' anger in the school setting as well as their ability to recognize expressions of anger in children's faces in a dynamic emotion recognition task. Results revealed that, even when controlling for teachers' age and gender, teachers' belief that children's anger was useful and valuable in the school setting was associated with teachers' accuracy at recognizing anger expressions in children's faces. The belief that children's anger was harmful and not conducive to learning, however, was not associated with teachers' accuracy at recognizing children's anger expressions. These findings suggest that certain everyday beliefs matter for predicting skill in recognizing specific emotion-related cues.
Project description:BackgroundResearchers should examine existing evidence to determine the need for a new study. It is unknown whether developers evaluate existing evidence to justify new cardiovascular clinical prediction rules (CPRs).ObjectiveWe aimed to assess whether authors of cardiovascular CPRs cited existing CPRs, why some authors did not cite existing CPRs, and why they thought existing CPRs were insufficient.MethodDerivation studies of cardiovascular CPRs from the International Register of Clinical Prediction Rules for Primary Care were evaluated. We reviewed the introduction sections to determine whether existing CPRs were cited. Using thematic content analysis, the stated reasons for determining existing cardiovascular CPRs insufficient were explored. Study authors were surveyed via e-mail and post. We asked whether they were aware of any existing cardiovascular CPRs at the time of derivation, how they searched for existing CPRs, and whether they thought it was important to cite existing CPRs.ResultsOf 85 derivation studies included, 48 (56.5%) cited existing CPRs, 33 (38.8%) did not cite any CPR, and four (4.7%) declared there was none to cite. Content analysis identified five categories of existing CPRs insufficiency related to: (1) derivation (5 studies; 11.4% of 44), (2) construct (31 studies; 70.5%), (3) performance (10 studies; 22.7%), (4) transferability (13 studies; 29.5%), and (5) evidence (8 studies; 18.2%). Authors of 54 derivation studies (71.1% of 76 authors contacted) responded to the survey. Twenty-five authors (46.3%) reported they were aware of existing CPR at the time of derivation. Twenty-nine authors (53.7%) declared they conducted a systematic search to identify existing CPRs. Most authors (90.7%) indicated citing existing CPRs was important.ConclusionCardiovascular CPRs are often developed without citing existing CPRs although most authors agree it is important. Common justifications for new CPRs concerned construct, including choice of predictor variables or relevance of outcomes. Developers should clearly justify why new CPRs are needed with reference to existing CPRs to avoid unnecessary duplication.
Project description:To ascertain the frequency of self-reported anger and depression in levetiracetam (LEV). We compared patients with epilepsy (PWE) taking LEV with PWE taking other antiepileptic drugs (AEDs). All PWE and controls submitted information to the UK AED register. We analysed the data of 418 PWE and 41 control participants. 158 participants took LEV in monotherapy or as part of polypharmacotherapy, 260 PWE took other AED. All PWE and controls completed the Liverpool Adverse Event Profile (LAEP) which includes items on anger and depression quantified on a four-point Likert scale, with 1 indicating that there was never a problem; 2, rarely a problem; 3, sometimes a problem and 4, always or often a problem. 49% of PWE on LEV and 39% on AED other than LEV reported anger as sometimes or always being a problem (p=0.042). 48% of PWE on LEV and 45% on AED other than LEV reported depression as sometimes or always being a problem (p=0.584). 7% of control participants reported anger as sometimes being a problem and 93% reported anger as never or rarely being a problem. Depression was never a problem in 75% of controls and rarely a problem in 25%. Anger and depression were more frequently reported as a problem by PWE than by control participants. Our observational register of self-reported symptoms suggested anger being more often a problem in patients taking LEV than in PWE taking other AED. PWE should be informed about this potential problem of LEV.