Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors

Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein nanoparticle (aNP) that stably incorporates siRNA into its core. We then created a comprehensive library of aNP formulations and extensively characterized their physicochemical properties and in vitro performance. From this library, we selected eight representative aNP-siRNA formulations and evaluated their ability to silence lysosomal-associated membrane protein 1 (Lamp1) expression in immune cell subsets in mice after intravenous administration. Using the most effective aNP identified from the screening process, we tested the platform’s potential for therapeutic gene silencing in a syngeneic murine tumour model. We also demonstrated the aNP platform’s suitability for splice-switching with antisense oligonucleotides and for protein production with messenger RNA by myeloid progenitor cells in the bone marrow. Our data indicate that the aNP platform holds translational potential for delivering various types of nucleic acid therapeutics to myeloid cells and their progenitors

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

The development of the Russian domestic gas market: historical perspective, current developments and strategy for the future

The European gas market has been in a process of liberalization for the last decade. To European policy makers, Russia is mostly viewed as an exporter of natural gas. However, the Russian domestic gas market has also seen several developments in recent years. This paper will provide an overview of the most important developments and regulatory changes on the domestic Russian gas market. The overview reveals the development of the market starting from the 1900s but with a particular emphasis on the period 2000-2017. The paper concludes with a section about the expected future developments on the domestic gas market in Russia

The development of the Russian domestic gas market: historical perspective, current developments and strategy for the future

The European gas market has been in a process of liberalization for the last decade. To European policy makers, Russia is mostly viewed as an exporter of natural gas. However, the Russian domestic gas market has also seen several developments in recent years. This paper will provide an overview of the most important developments and regulatory changes on the domestic Russian gas market. The overview reveals the development of the market starting from the 1900s but with a particular emphasis on the period 2000-2017. The paper concludes with a section about the expected future developments on the domestic gas market in Russia

Adolescent's Willingness to Adopt a More Plant-Based Diet: A Theory-Based Interview Study

A plant-based diet is more sustainable, and research suggests that adolescents obtain health benefits from adopting a more plant-based diet (e.g., improved weight control, increased cardiovascular health). However, it is still unclear what factors promote/hinder their intention to attain such a dietary habit. The aim of the present study was to examine factors affecting adolescents' willingness to consume more plant-based foods. In a theory-based interview study, using the Reasoned Action Approach as framework, adolescents were interviewed concerning their reasons for their (un)willingness to adopt a more plant-based diet. A total of 11 adolescents (15/16 years old; 7 girls, 4 boys) were recruited and interviewed at two secondary schools in the Dutch Province of Limburg, the Netherlands. None of the interviewees reported being vegan/vegetarian/flexitarian. The interviewed adolescents overall expressed little interest in adopting a more plant-based diet. They appeared to have little knowledge of what would comprise a more plant-based diet and showed a lack of awareness of the benefits for personal and planet health. Further, most participants indicated lacking skills to prepare plant-based meals. Despite that, they felt confident they would be able to consume a much more plant-based diet for a definite period. Most importantly, the low intention to consume more plant-based food options was explained by the perceived (or expected) poor taste of these foods. We conclude that education on the plant-based diet (i.e., increasing awareness of the benefits, and skills to procure or prepare a plant-based meal) might increase both knowledge and plant-based food familiarity. The latter being important as food familiarity is key in promoting its acceptance

Cognitive subtypes of mathematics learning difficulties in primary education

It has been asserted that children with mathematics learning difficulties (MLD) constitute a heterogeneous group. To date, most researchers have investigated differences between predefined MLD subtypes. Specifically MLD children are frequently categorized a priori into groups based on the presence or absence of an additional disorder, such as a reading disorder, to examine cognitive differences between MLD subtypes. In the current study 226 third to six grade children (M age=131 months) with MLD completed a selection of number specific and general cognitive measures. The data driven approach was used to identify the extent to which performance of the MLD children on these measures could be clustered into distinct groups. In particular, after conducting a factor analysis, a 200 times repeated K-means clustering approach was used to classify the children's performance. Results revealed six distinguishable clusters of MLD children, specifically (a) a weak mental number line group, (b) weak ANS group, (c) spatial difficulties group, (d) access deficit group, (e) no numerical cognitive deficit group and (f) a garden-variety group. These findings imply that different cognitive subtypes of MLD exist and that these can be derived from data-driven approaches to classification. These findings strengthen the notion that MLD is a heterogeneous disorder, which has implications for the way in which intervention may be tailored for individuals within the different subtypes

The variability in the effect of additional education on different mathematics skills in primary school - A regression discontinuity analysis

This paper explores the variability in the effect of an additional year of education on different basic mathematical skills, which are taught to children and explicitly repeated at different points in time during elementary school. In addition, the role of child specific characteristics and the role of the school is addressed. Using a regression discontinuity approach, we estimate the local education effect for a range of successive elementary school grade cohorts at six schools in the Netherlands, while including child specific characteristics and school fixed effects. The results indicate that the effect of education is contingent upon the mathematical skills and grade levels studied. A significant education effect is observed the year after children have first learned a mathematical skill and in the last year of primary school, which can be explained by the additional focus that is being put on elementary mathematics skills in these years. Furthermore, the outcomes suggest that children’s multiplication skills are significantly lower if their school emphasizes child centered, natural learning and multigrade teaching instead of traditional classroom learning

The differential effect of a non-compulsory basic mathematics skills practice tool across achievement subgroups and mathematical skills practice tools across achievement subgroups and mathematics domains - a randomized field experiment

This paper examines the differential effect of a computerized, non-compulsory supplementary practice tool in a sample of first-year secondary students (N = 355) using an experimental design. Additionally, students’ practice behavior and its association with teacher factors were investigated. The results show that the practice tool was variably effective across the skill distribution of children and distinct mathematics domains (numbers, proportions and measurement). The practice tool proved particularly effective for low-achievers, who significantly benefited from the practice tool in all mathematics domains. For middle-achievers benefits were only observed in the domain of proportions. Furthermore, it is shown that a significant part of the variance in students’ practice behavior is explained by teacher factors. Therefore, the results indicate that for maximum efficiency students may be given selective access to domains and teachers need to incentivize the students to practice on a regular basis

The impact of the nutri-score on food choice: A choice experiment in a Dutch supermarket

Front-of-package (FOP) nutrition labels are placed on products to help consumers make healthy food choices. A lab-in-field experiment was conducted to test the effectiveness of two FOP labels in promoting healthy food choices among Dutch consumers, and to examine whether dieters and health conscious shoppers are more likely to use the FOP labels. In addition, it was examined whether the placement of relatively "good" FOP label scores on products might inadvertently lead to increases in serving sizes. Participants (N = 300) consisted of Dutch consumers shopping for groceries in a local supermarket. They were randomly assigned to one of three conditions (Nutri-score, Multiple Traffic Light (MTL) label, or no label control condition), presented with six different (labeled) cereals, and asked to make a choice. Next, participants were shown a product with a relatively good label score and selected their desired serving size. The results show that the Nutri-score promotes choice of the healthiest cereal. Dieting behaviour and health conscious shopping did not moderate this effect, and the labels did not affect serving size selection. Overall, the study provides evidence for the Nutri-score to promote healthy food choices among Dutch consumers