Antibiotics Shaping Bacterial Genome: Deletion of an IS91 Flanked Virulence Determinant upon Exposure to Subinhibitory Antibiotic Concentrations

The nucleoid-associated proteins Hha and YdgT repress the expression of the toxin α-hemolysin. An Escherichia coli mutant lacking these proteins overexpresses the toxin α-hemolysin encoded in the multicopy recombinant plasmid pANN202-312R. Unexpectedly, we could observe that this mutant generated clones that no further produced hemolysin (Hly-). Generation of Hly- clones was dependent upon the presence in the culture medium of the antibiotic kanamycin (km), a marker of the hha allele (hha::Tn5). Detailed analysis of different Hly- clones evidenced that recombination between partial IS91 sequences that flank the hly operon had occurred. A fluctuation test evidenced that the presence of km in the culture medium was underlying the generation of these clones. A decrease of the km concentration from 25 mg/l to 12.5 mg/l abolished the appearance of Hly- derivatives. We considered as a working hypothesis that, when producing high levels of the toxin (combination of the hha ydgT mutations with the presence of the multicopy hemolytic plasmid pANN202-312R), the concentration of km of 25 mg/l resulted subinhibitory and stimulated the recombination between adjacent IS91 flanking sequences. To further test this hypothesis, we analyzed the effect of subinhibitory km concentrations in the wild type E. coli strain MG1655 harboring the parental low copy number plasmid pHly152. At a km concentration of 5 mg/l, subinhibitory for strain MG1655 (pHly152), generation of Hly- clones could be readily detected. Similar results were also obtained when, instead of km, ampicillin was used. IS91 is flanking several virulence determinants in different enteric bacterial pathogenic strains from E. coli and Shigella. The results presented here evidence that stress generated by exposure to subinhibitory antibiotic concentrations may result in rearrangements of the bacterial genome. Whereas some of these rearrangements may be deleterious, others may generate genotypes with increased virulence, which may resume infection

Efficacy of a self-applied online program to promote resilience and coping skills in university students in four Spanish-speaking countries: study protocol for a randomized controlled trial

Background: There is evidence of a high prevalence of depression and anxiety in university students. Therefore, college time is a key period where prevention of mental disorders through interventions that promote resilience and mental health can be relevant. Currently, there are interventions available, but these are insufficient for those who need them. Online interventions are tools that can facilitate global accessibility and are easy for young people to use. CORE (Cultivating Our Resilience) is a self-administered online program, based on Ryff’s psychological well-being model, to promote resilience and coping skills in university students at risk of developing symptoms of depression or anxiety. The objective is to evaluate the effectiveness of this intervention protocol in comparison with an active control condition targeting healthy lifestyle, and a waiting list control condition. The study will be conducted in four populations of Spanish-speaking university students (Spain, Argentina, Colombia, and Mexico). Methods: The study design is a randomized controlled trial (RCT). At least 324 university students will be randomly assigned to three conditions: 1) CORE, a 6-week training program to improve resilience; 2) HLP, a 6-week training to promote a healthy lifestyle; and 3) WL, waiting list control condition. The primary outcome measure will be the Connor-Davidson resilience scale. Additionally, measures of anxiety, depression, quality of life and socio-demographic variables (age, sex, incomes, marital status, among others) will be collected. Participants will be evaluated at pre-treatment, after each module, 6 weeks after allocation, and at 3-month follow-up. Intention-to-treat and per-protocol analyses will be performed. Discussion: The results of this study will contribute to research on Internet-administered interventions and the implementation of a protocol that includes a series of components designed to improve resilience and coping skills, increase psychological well-being, and prevent depression and anxiety disorders in Spanish-speaking university students. In addition, avenues will be opened up for new research on the effectiveness of these interventions focused on the prevention and promotion of mental health in Spanish-speaking countries

Aplicaciones en la región de Murcia de la información de ocupación de suelo en España (SIOSE)

Finalizadas las tareas del proyecto del Sistema de Información de Ocupación del Suelo en España (SIOSE), se plantea el aprovechamiento de la información obtenida de las múltiples bases de datos geográficas. En esta nueva fase, se ha propuesto desarrollar herramientas que faciliten la explotación de dichas bases de datos geográficas, mediante un conjunto de aplicaciones software. Además, y como un primer paso hacia la integración dentro de una infraestructura de datos espaciales (IDE) regional, ofrecer servicios basados en los estándares de publicación de información espacial en internet según el Open Geospatial Consortium (OGC), que permitan la visualización y consul- ta de los datos elaborados, con el objetivo de su difusión con el mayor grado posible.With the project completed, the information system of land use in Spain (SIOSE) takes the opportunity to use the information obtained from multiple geographic databases. In this new phase, it is proposed to develop tools that facilitate the work of these geographic databases through a set of software applications. In addition, as a first step towards integration into a regional spatial data infrastructure (SDI), providing standards-based services for spatial information published online by the Open Geospatial Consortium (OGC) which enable visualization and query the data produced with the aim of its distribution with the greatest possible degree

Decision making impairment: A shared vulnerability in obesity, gambling disorder and substance use disorders?

Introduction: Addictions are associated with decision making impairments. The present study explores decision making in Substance use disorder (SUD), Gambling disorder (GD) and Obesity (OB) when assessed by Iowa Gambling Task (IGT) and compares them with healthy controls (HC). Methods: For the aims of this study, 591 participants (194 HC, 178 GD, 113 OB, 106 SUD) were assessed according to DSM criteria, completed a sociodemographic interview and conducted the IGT. Results: SUD, GD and OB present impaired decision making when compared to the HC in the overall task and task learning, however no differences are found for the overall performance in the IGT among the clinical groups. Results also reveal some specific learning across the task patterns within the clinical groups: OB maintains negative scores until the third set where learning starts but with a less extend to HC, SUD presents an early learning followed by a progressive although slow improvement and GD presents more random choices with no learning. Conclusions: Decision making impairments are present in the studied clinical samples and they display individual differences in the task learning. Results can help understanding the underlying mechanisms of OB and addiction behaviors as well as improve current clinical treatments

Differential Regulation of Horizontally Acquired and Core Genome Genes by the Bacterial Modulator H-NS

Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic