Tackling AMR from a multidisciplinary perspective: a primer from education and psychology

Antimicrobial resistance (AMR) is currently one of the most concerning threats in public health. The efforts to tackle the problem require a global One Health approach, using multidisciplinary approaches and a thorough understanding of the topic both by the general public and the experts. Currently, the lack of a shared mental model of the problem, the absence of a sense of responsibility amongst the different actors and a deficient education on the topic burden the efforts to slow down the emergency and spread of antimicrobial resistant infections. We here propose a multidisciplinary approach to tackle the AMR problem, taking into consideration not only the input from the biological and medical sciences but also the input from the social sciences. Specifically, we suggest strategies from education and psychology to increase awareness about antimicrobial resistance and to implement more effective interventions. Finally, we advocate for a comprehensive and a solidaristic model as the only solution for a problem which knows no borders. As such, political will and international cooperation will be key to achieve the desired change in antibiotic resistance trend

Positive selection inhibits plasmid coexistence in bacterial genomes

Plasmids play an important role in bacterial evolution by transferring niche-adaptive functional genes between lineages, thus driving genomic diversification. Bacterial genomes commonly contain multiple, coexisting plasmid replicons, which could fuel adaptation by increasing the range of gene functions available to selection and allowing their recombination. However, plasmid coexistence is difficult to explain because the acquisition of plasmids typically incurs high fitness costs for the host cell. Here, we show that plasmid coexistence was stably maintained without positive selection for plasmid-borne gene functions and was associated with compensatory evolution to reduce fitness costs. In contrast, with positive selection, plasmid coexistence was unstable despite compensatory evolution. Positive selection discriminated between differential fitness benefits of functionally redundant plasmid replicons, retaining only the more beneficial plasmid. These data suggest that while the efficiency of negative selection against plasmid fitness costs declines over time due to compensatory evolution, positive selection to maximize plasmid-derived fitness benefits remains efficient. Our findings help to explain the forces structuring bacterial genomes: coexistence of multiple plasmids in a genome is likely to require either rare positive selection in nature or nonredundancy of accessory gene functions among the coexisting plasmids

Are There Gender Differences in Social Cognition in First-Episode Psychosis?

Altres ajuts: This research was funded by the Instituto de Salud Carlos III (Spanish Government, PI11/01347, PI14/00044, and PI18/00212) by the Fondo Europeo de Desarrollo Regional (FEDER), Health Department of Catalonia, PERIS call (SLT006/17/00231), Progress and Health Foundation of the Andalusian Regional Ministry of Health, grant PI-0634/2011 and PI-0193/ 2014, Obra Social La Caixa (RecerCaixa call 2013), CERCA Programme/Generalitat de Catalunya, Obra Social Sant Joan de Déu (BML) and by FI19/00062 (Ayudas para la contratación de personal predoctoral, Luciana Díaz-Cutraro is a beneficiary of a Predoctoral Training Grant in Health Research).The aim of this study was to explore gender differences in social cognition in a sample of first-episode psychosis (FEP). An observational descriptive study was performed with 191 individuals with FEP. Emotion perception was assessed using the Faces Test, theory of mind was assessed using the Hinting Task, and attributional style was assessed using the Internal, Personal and Situational Attributions Questionnaire. No gender differences were found in any of the social cognitive domains. Our results suggest that men and women with FEP achieve similar performances in social cognition. Therefore, targeting specific needs in social cognition regarding gender may not be required in early interventions for psychosis

Males and females with first episode psychosis present distinct profiles of social cognition and metacognition

Altres ajuts: Royal Society of New Zealand - Marsden (E2987-3648) ; Obra Social La Caixa (RecerCaixa call 2013) ; Obra Social Sant Joan de Déu BML (RTI2018-100927-J-I00) ; Ministerio Regional de Salud AndaluzDeficits in social cognition and metacognition impact the course of psychosis. Sex diferences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with frst-episode psychosis completed a clinical, neuropsychological, social cognitive, and metacognitive assessment. Subsequent latent profle analysis split by sex yielded two clusters common to both sexes (a Homogeneous group, 53% and 79.3%, and an Indecisive group, 18.3% and 8.6% of males and females, respectively), a specifc male profle characterized by presenting jumping to conclusions (28.7%) and a specifc female profle characterized by cognitive biases (12.1%). Males and females in the homogeneous profle seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological defcits. Females with cognitive biases were younger and had lower self-esteem. These results suggest that males and females may beneft from specifc targeted treatment and highlights the need to consider sex when planning interventions

Persons with first episode psychosis have distinct profiles of social cognition and metacognition

Altres ajuts: Obra Social La Caixa (RecerCaixa call 2013), by the Agencia Estatal de Investigación (AEI, Spain). Junta de Andalucía: PI-0634/2011; PI-0193/2014.Subjects with first-episode psychosis experience substantial deficits in social cognition and metacognition. Although previous studies have investigated the role of profiles of individuals in social cognition and metacognition in chronic schizophrenia, profiling subjects with first-episode psychosis in both domains remains to be investigated. We used latent profile analysis to derive profiles of the abilities in 174 persons with first-episode psychosis using the Beck's Cognitive Insight Scale, the Faces Test, the Hinting Task, the Internal, Personal and Situational Attributions Questionnaire, and the Beads Task. Participants received a clinical assessment and a neuropsychological assessment. The best-fitting model was selected according to the Bayesian information criterion (BIC). We assessed the importance of the variables via a classification tree (CART). We derived three clusters with distinct profiles. The first profile (33.3%) comprised individuals with low social cognition. The second profile (60.9%) comprised individuals that had more proneness to present jumping to conclusions. The third profile (5.7%) presented a heterogeneous profile of metacognitive deficits. Persons with lower social cognition presented worse clinical and neuropsychological features than cluster 2 and cluster 3. Cluster 3 presented significantly worst functioning. Our results suggest that individuals with FEP present distinct profiles that concur with specific clinical, neuropsychological, and functional challenges. Each subgroup may benefit from different interventions

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Altres ajuts: PERIS call (grant no. SLT006/17/00231); the Progress and Health Foundation of the Andalusian Regional Ministry of Health (grant no. PI-0634/2011 and PI-0193/2014); Obra Social La Caixa (RecerCaixa call 2013); CERCA Programme/Generalitat de Catalunya; Obra Social Sant Joan de Déu (BML); and FI19/00062 (Ayudas para la Contratación de Personal Predoctoral).A protective effect has traditionally been attributed to estrogen in psychotic disorders. The aim of this study was to investigate cumulative lifetime estrogen by assessing the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and the age of menarche, measuring their effects on symptoms, cognition, social cognition, and metacognition. As it was not possible to directly measure cumulative estrogen levels over the lifetime of a patient, the study sample was composed of 42 women with first-episode psychosis; estrogen levels were inferred by the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and menarche. All patients were assessed with a battery of questionnaires using the BDI, PSYRATS, PANSS, STROOP, TAVEC, WSCT, IPSAQ, and BCIS questionnaires. The results related to menstrual cycle length showed a relationship with memory; specifically, shorter cycles with semantic strategies (p = 0.046) and longer cycles with serial strategies in the short term (p = 0.005) as well as in the long term (p = 0.031). The results also showed a relationship with perseverative errors (p = 0.035) and self-certainty (p = 0.049). Only personalized bias (p = 0.030) was found to be significant in relation to the age at menarche. When analyzing the differences in years of difference between the age at menarche and the onset of psychotic symptoms, the results indicated lower scores in women with a smaller difference between both events in memory (short-term (p = 0.050), long-term (p = 0.024), intrusions (p = 0.013), and recognition (p = 0.043)) and non-perseverative errors (p = 0.024). No relationship was found between symptoms and menstrual characteristics. The investigatory outcomes seem to indicate a relationship between estrogen cumulative effects and the memory domain. More in-depth investigations in the field are necessary in order to improve personalized treatment in women with psychosis

Heterogeneity in Response to MCT and Psychoeducation : A Feasibility Study Using Latent Class Mixed Models in First-Episode Psychosis

Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatments

Performance Evaluation of the Dual Ring MAMMI breast PET

[Otros] MAMMI is a dedicated breast positron emission tomograph (PET) based on monolythic LYSO crystals, with a transaxial field of view (FOV) of 170 mm. It has been upgraded by adding a second ring of detectors that extends the axial FOV from 40 mm to 94.4 mm, in order to improve its sensitivity and reduce the acquisition time. In this work we present the performance evaluation of the dual ring MAMMI breast PET and a discussion about the contribution of the addition of a second ring of detectors, the compensation of the detector blur and the increase of the scintillator thickness. Experimental measurements suggested on NEMA NU 4-2008 and NEMA NU 2-2007 have been conveniently adapted to the dimensions of the MAMMI. The addition of the second ring of detectors leads to a rise of the sensitivity from 1.8% to 3.6%. The spatial resolution at one-fourth of the axial FOV (1.5 mm axial, 1.6 mm tangential, 1.7 mm radial) is slightly better than that measured at the axial center (1.9 mm axial, 1.8 mm tangential and radial), because of the 14 mm gap in between detection rings. The results obtained after the evaluation reflect a substantial performance improvement, specially in the absolute sensitivity, because of the changes introduced in the MAMMI PET.This work was supported in part bythe Spanish Plan Nacional de Investigacion Científica, Desarrollo e Innovación Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013Soriano, A.; Sánchez, F.; Carrilero, V.; Pardo, A.; Vidal San Sebastian, LF.; Vazquez, C.; Barbera, J.... (2013). Performance Evaluation of the Dual Ring MAMMI breast PET. IEEE. 1-4. https://doi.org/10.1109/NSSMIC.2013.6829103S1

periscope: sub-genomic RNA identification in SARS-CoV-2 genomic sequencing data

We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L which is located in the 5’ UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5’ end of all sgRNA. We applied periscope to 1,155 SARS-CoV-2 genomes from Sheffield, UK and validated our findings using orthogonal datasets and in vitro cell systems. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sgRNA. We were able to detect all canonical sgRNAs at expected abundances, with the exception of ORF10. A number of recurrent non-canonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/− cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing datasets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA