Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy

Bacterial pathogens cause severe infections worldwide in livestock and in humans, and antibiotic resistance further increases the importance of prophylactic vaccines. Inactivated bacterial vaccines (bacterins) are usually produced via incubation of the pathogen with chemicals such as formaldehyde, which is time consuming and may cause loss of immunogenicity due to the modification of structural components. We evaluated low-energy electron irradiation (LEEI) as an alternative method to generate a bacterin. Rodentibacter pneumotropicus, an invasive Gram-negative murine pathogen, was inactivated with LEEI and formaldehyde. LEEI resulted in high antigen conservation, and LPS activity was significantly better maintained when compared with formaldehyde treatment. Immunization of mice with LEEI-inactivated R. pneumotropicus elicited a strong immune response with no detectable bacterial burden upon sublethal challenge. The results of this study suggest the inactivation of bacteria with LEEI as an alternative, fast and efficient method to generate bacterial vaccines with increased efficacy

Coexistence of adenomyosis uteri and endometrial cancer is associated with an improved prognosis compared with endometrial cancer only

The present study aimed to identify differences in protein expression in cases of endometrioid endometrial cancer (EEC) with and without coexisting adenomyosis uteri (AM), and to evaluate the histopathological and prognostic distinctions. The total cohort included 22 patients in Group A (patients with concomitant AM and EEC) and 35 patients in Group B (patients affected only by EEC). Evaluation of the following factors was performed: Tumour grade, International Federation of Gynaecology and Obstetrics (FIGO) stage, survival, and expression of estrogen receptor beta (ER beta), glycodelin and inhibin beta B. Group A (AM and EEC) was associated with a lower tumour grade (G1, 90.9 vs. 45.7%;P=0.001) and a lower FIGO stage (FIGO stage I, 100 vs. 80%;P=0.002) compared with Group B (EEC only). In the survival analysis, Group A was associated with a significantly higher 5-year survival rate (95 vs. 82%;P=0.024) than Group B. In addition, the expression of ER beta in Group A was significantly higher (P<0.001), whereas the expression of glycodelin is significantly lower (P=0.028), compared with Group B. The results of the present study indicate that the presence of AM in cases of EEC may be a positive prognostic factor

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire

Purpose: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. Methods: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach’s α, and intra-class correlation coefficient). Results: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68–0.92) and test–retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. Conclusion: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.publishedVersio

Social Deprivation Is Associated With Lower Access to Pre-emptive Kidney Transplantation and More Urgent-Start Dialysis in the Pediatric Population

Introduction Socioeconomic status (SES) is recognized as an important determinant of kidney health. We aimed to evaluate the association of social deprivation with different indicators at kidney replacement therapy (KRT) initiation in the French pediatric metropolitan population. Methods All patients with end-stage kidney disease (ESKD) who started KRT before 20 years old in France between 2002 and 2015 were included. We investigated different indicators at KRT initiation, which are as follows: KRT modality (dialysis vs. pre-emptive transplantation), late referral to a nephrologist, and dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD], urgent vs. planned start of dialysis, use of catheter vs. use of fistula for HD vascular access). An ecological index (European Deprivation Index [EDI]) was used as a proxy for social deprivation. Results A total of 1115 patients were included (males 59%, median age at dialysis 14.4 years, glomerular/vascular diseases 36.8%). The most deprived group represented 38.7% of the patients, suggesting pediatric patients with ESKD come from a more socially deprived background. The most deprived group was more likely to initiate KRT with dialysis versus kidney transplantation. Among patients on HD, the odds of starting treatment in emergency with a catheter was >2-fold higher for the most deprived compared with the least deprived children (adjusted odds ratio [aOR] 2.35, 95% CI 1.16–4.78). Conclusion Children from the most deprived area have lower access to pre-emptive transplantation, have lower access to PD, tend to be late referred to a nephrologist, and have more urgent initiation of HD with a catheter

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Letters into exile: narratological strategies and identity-forming storytelling in the post-war correspondence of the Ernst Levin Collection (1946-1962)

This thesis aims to contribute to the field of epistolary research, research on ego-documents as well as cultural and literary studies of the fin de siècle, the interbellum period and the post-World War Two era in Germany. In my thesis I conduct a textual analysis of a lengthy correspondence and thus aim to further fill this gap in working with letters. I examine the correspondence of painter Max Unold (1885-1964) and writer Reinhard Koester (1885-1956) with the Jewish neurologist Ernst Levin (1887-1975) and his wife Anicuta Belau (1886-1965) who emigrated to Edinburgh in 1933 and 1938. The approach of undertaking a close reading analysis of letters has been undervalued in research. Letters have often been conceptualised as historical documents. While there is considerable merit to such work, it neglects the carefully crafted linguistic properties of such texts. Whilst a small number of previous works have taken on the approach of analysing the language of letters in order to gain insights into the writers’ communicative goals, their sentiments and cultural frames, this thesis aims to further map out the use of linguistic tools. I develop a new way of working with letters that provides insights into the writing patterns, literary devices, and linguistic strategies that letter writers use and what they seek to achieve by this. As I work with letters sent to those in exile by those who were not persecuted in the Third Reich and remained in Germany, I further make an original contribution to research by offering a different perspective on ‘migrant letters’. A close reading of the letter corpus identifies the strategies used by the letter writers and additionally discloses where these are borrowed from stylistically. My analysis illustrates how the letters function as platform for identity performances. With the thematic orientation of the individual chapters on spaces, the body, and the process of ageing, I also contribute to the linguistic discourse on these themes. Moreover, the focus on these topoi is valuable in further refining the dynamic and linguistic construction of the postwar friendship between Jewish émigrés and their friends who participated in the perpetuation of the Third Reich

Modulation de l'activité des neurones entériques par le GABA et les polyamines

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF