Neurocognitive functioning following preeclampsia and eclampsia:a long-term follow-up study

ObjectiveWomen who suffered preeclampsia and eclampsia may report subjective cognitive difficulties in daily life, the interpretation of which is cumbersome, because these are affected by emotional factors. Previous studies only included preeclamptic women investigated shortly after pregnancy. We aimed to determine whether these subjective reports of cognitive difficulty could be interpreted as reflecting objective cognitive dysfunction. Therefore, cognitive functioning was assessed using standardized neurocognitive tests in both preeclamptic and eclamptic women several years following the index pregnancy.Study DesignForty-six formerly eclamptic, 51 formerly preeclamptic, and 48 control women who had normotensive pregnancies, age-matched, participated in this study. Average elapsed time since index pregnancy was 7 years. Neurocognitive tests were divided into 6 domains; visual perception, motor functions, working memory, long-term memory, attention, and executive functioning. Subjective cognitive functioning was measured by the Cognitive Failures Questionnaire and anxiety/depression by the Hospital Anxiety and Depression Scale.ResultsBoth preeclamptic and eclamptic women performed worse on the motor functions domain (P < .05), without differences on the other domains. They scored worse on the Cognitive Failures Questionnaire (P < .01), the Hospital Anxiety and Depression Scale anxiety (P < .01), and depression (P < .05) subscales.ConclusionWomen who suffered eclampsia and/or preeclampsia demonstrate no objective cognitive impairment as compared with controls. Contrary to the well-structured test setting, both groups do report more cognitive failures, which are thought to reflect neurocognitive dysfunction in complex, stressful daily-life situations. Such report of cognitive failures may be compounded by anxiety and depression. Future studies should focus on the relationship of neurocognitive functioning with structural cerebral abnormalities

Working mechanisms of the use and acceptability of ecological momentary interventions:A realist evaluation of a guided self-help ecological momentary intervention targeting self-esteem

BackgroundTechnology improves accessibility of psychological interventions for youth. An ecological momentary intervention (EMI) is a digital intervention geared toward intervening in daily life to enhance the generalizability and ecological validity, and to be able to intervene in moments most needed. Identifying working mechanisms of the use of ecological momentary interventions might generate insights to improve interventions.MethodsThe present study investigates the working mechanisms of the use and acceptability of an ecological momentary intervention, named SELFIE, targeting self-esteem in youth exposed to childhood trauma, and evaluates under what circumstances these mechanisms of use and acceptability do or do not come into play. A realist evaluation approach was used for developing initial program theories (data: expert interviews and a stakeholders focus group), and subsequently testing (data: 15 interviews with participants, a focus group with therapists, debriefing questionnaire), and refining them.ResultsThe SELFIE intervention is offered through a smartphone application enabling constant availability of the intervention and thereby increasing accessibility and feasibility. When the intervention was offered on their personal smartphone, this enhanced a sense of privacy and less hesitance in engaging with the app, leading to increased disclosure and active participation. Further, the smartphone application facilitates the practice of skills in daily life, supporting the repeated practice of exercises in different situations leading to the generalizability of the effect. Buffering against technical malfunction seemed important to decrease its possible negative effects.ConclusionsThis study enhanced our understanding of possible working mechanisms in EMIs, such as the constant availability supporting increased accessibility and feasibility, for which the use of the personal smartphone was experienced as a facilitating context. Hereby, the current study contributes to relatively limited research in this field. For the field to move forward, mechanisms of use, and acceptability of EMIs need to be understood. It is strongly recommended that alongside efficacy trials of an EMI on specific target mechanisms, a process evaluation is conducted investigating the working mechanisms of use.Trial registrationThe current paper reports on a realist evaluation within the SELFIE trial (Netherlands Trial Register NL7129 (NTR7475))

Transdiagnostic Ecological Momentary Intervention for Improving Self-Esteem in Youth Exposed to Childhood Adversity:The SELFIE Randomized Clinical Trial

Importance: Targeting low self-esteem in youth exposed to childhood adversity is a promising strategy for preventing adult mental disorders. Ecological momentary interventions (EMIs) allow for the delivery of youth-friendly, adaptive interventions for improving self-esteem, but robust trial-based evidence is pending.Objective: To examine the efficacy of SELFIE, a novel transdiagnostic, blended EMI for improving self-esteem plus care as usual (CAU) compared with CAU only.Design, Setting, and Participants: This was a 2-arm, parallel-group, assessor-blinded, randomized clinical trial conducted from December 2018 to December 2022. The study took place at Dutch secondary mental health services and within the general population and included youth (aged 12-26 years) with low self-esteem (Rosenberg Self-Esteem Scale [RSES] &lt;26) exposed to childhood adversity.Interventions: A novel blended EMI (3 face-to-face sessions, email contacts, app-based, adaptive EMI) plus CAU or CAU only.Main Outcomes and Measures: The primary outcome was RSES self-esteem at postintervention and 6-month follow-up. Secondary outcomes included positive and negative self-esteem, schematic self-beliefs, momentary self-esteem and affect, general psychopathology, quality of life, observer-rated symptoms, and functioning.Results: A total of 174 participants (mean [SD] age, 20.7 [3.1] years; 154 female [89%]) were included in the intention-to-treat sample, who were primarily exposed to childhood emotional abuse or neglect, verbal or indirect bullying, and/or parental conflict. At postintervention, 153 participants (87.9%) and, at follow-up, 140 participants (80.5%), provided primary outcome data. RSES self-esteem was, on average, higher in the experimental condition (blended EMI + CAU) than in the control condition (CAU) across both postintervention and follow-up as a primary outcome (B = 2.32; 95% CI, 1.14-3.50; P &lt; .001; Cohen d-type effect size [hereafter, Cohen d] = 0.54). Small to moderate effect sizes were observed suggestive of beneficial effects on positive (B = 3.85; 95% CI, 1.83-5.88; P &lt; .001; Cohen d = 0.53) and negative (B = −3.78; 95% CI, −6.59 to −0.98; P = .008; Cohen d = −0.38) self-esteem, positive (B = 1.58; 95% CI, 0.41-2.75; P = .008; Cohen d = 0.38) and negative (B = −1.71; 95% CI, −2.93 to −0.48; P = .006; Cohen d = −0.39) schematic self-beliefs, momentary self-esteem (B = 0.29; 95% CI, 0.01-0.57; P = .04; Cohen d = 0.24), momentary positive affect (B = 0.23; 95% CI, 0.01-0.45; P = .04; Cohen d = 0.20), momentary negative affect (B = −0.33; 95% CI, −0.59 to −0.03, P = .01, Cohen d = −0.27), general psychopathology (B = −17.62; 95% CI, −33.03 to −2.21; P = .03; Cohen d = −0.34), and quality of life (B = 1.16; 95% CI, 0.18-2.13; P = .02; Cohen d = 0.33) across postintervention and follow-up. No beneficial effects on symptoms and functioning were observed.Conclusions and Relevance: A transdiagnostic, blended EMI demonstrated efficacy on the primary outcome of self-esteem and signaled beneficial effects on several secondary outcomes. Further work should focus on implementing this novel EMI in routine public mental health provision.Trial Registration Dutch Trial Register Identifier: NL7129(NTR7475

Discontinuing Inappropriate Medication in Nursing Home Residents (DIM-NHR Study):Protocol of a cluster randomised controlled trial

INTRODUCTION: Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents' quality of life. The objective of the 'Discontinuing Inappropriate Medication in Nursing Home Residents' (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. METHODS: A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient's elderly care physician in collaboration with a pharmacist. ANALYSIS: Primary outcomes-the difference in proportion of residents who successfully discontinued inappropriate medication between the intervention and control group at follow-up. Secondary outcomes-undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: Participant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed. TRIAL REGISTRATION NUMBER: This study has been registered at http://www.ClinicalTrials.gov (trial registration number: NCT01876095)

Selection during Early Life Stages and Local Adaptation in Arabidopsis thaliana

Organisms are often adapted to their local environment, but the role of early life stages in adaptive differentiation among populations remains poorly known. The aim of my thesis was to investigate the contribution of early life stages to the magnitude and genetic basis of local adaptation, and to identify the underlying adaptive traits. For this, I used two natural populations of the annual plant Arabidopsis thaliana from Italy and Sweden, and a Recombinant Inbred Line (RIL) population derived from a cross between these populations. By combining greenhouse and field experiments, Quantitative Trait Loci (QTL) mapping, and path analysis, I examined (1) the genetic basis of seed dormancy, (2) the contribution of differential seedling establishment to local adaptation, (3) among-year variation in selection during seedling establishment, (4) direct and indirect effects of seed dormancy and timing of germination on fitness, and (5) the adaptive value of the seed bank. I found that both the level and the genetic basis of seed dormancy were affected by the maternal environment. One major-effect QTL was identified in all maternal environments, which overlaps with the dormancy gene DELAY OF GERMINATION 1 (DOG1). Selection through seedling establishment success contributed strongly to local adaptation and genetic tradeoffs, and varied among years. Variation in seedling establishment and overall fitness among RILs could be explained by genetically based differences in seed dormancy and timing of germination. Seed dormancy affected fitness throughout the life cycle, by affecting the proportion of germinated seeds, and indirectly via effects on timing of germination, plant size and flowering time. My results suggest that a considerable portion of A. thaliana seeds enter the seed bank. I found genetic differences in dormancy cycling behaviour between the two populations, which could contribute to local adaptation. The value of a seed bank should be higher at the Swedish study site than at the Italian study site due to lower rate of seed mortality in the soil. Overall, the results of this thesis demonstrate that early life stages contribute strongly to both the magnitude and the genetics of local adaptation

Data from: Among-year variation in selection during early life stages and the genetic basis of fitness in Arabidopsis thaliana

Incomplete information regarding both selection regimes and the genetic basis of fitness limits our understanding of adaptive evolution. Among-year variation in the genetic basis of fitness is rarely quantified, and estimates of selection are typically based on single components of fitness, thus potentially missing conflicting selection acting during other life-history stages. Here, we examined among-year variation in selection on a key life-history trait and the genetic basis of fitness covering the whole life cycle in the annual plant Arabidopsis thaliana. We planted freshly-matured seeds of >200 recombinant inbred lines (RILs) derived from a cross between two locally-adapted populations (Italy and Sweden), and both parental genotypes at the native site of the Swedish population in three consecutive years. We quantified selection against the nonlocal Italian genotype, mapped quantitative trait loci (QTL) for fitness and its components, and quantified selection on timing of germination during different life stages. In all three years, the local Swedish genotype outperformed the non-local Italian genotype. However, both the contribution of early life stages to relative fitness, and the effects of fitness QTL varied among years. Timing of germination was under conflicting selection through seedling establishment vs. adult survival and fecundity, and both the direction and magnitude of net selection varied among years. Our results demonstrate that selection during early life stages and the genetic basis of fitness can vary markedly among years, emphasizing the need for multi-year studies considering the whole life cycle for a full understanding of natural selection and mechanisms maintaining local adaptation

Effects of primary seed dormancy on lifetime fitness of Arabidopsis thaliana in the field

Background and Aims Seed dormancy determines the environmental niche of plants in seasonal environments, and has consequences for plant performance that potentially go far beyond the seed and seedling stages. In this study, we examined the cascading effects of seed dormancy on the expression of subsequent life-history traits and fitness in the annual herb Arabidopsis thaliana. Methods We planted seeds of &gt;200 recombinant inbred lines (RILs) derived from a cross between two locally adapted populations (Italy and Sweden), and both parental genotypes at the native site of the Swedish population in three consecutive years. We quantified the relationship between primary seed dormancy and the expression of subsequent life-history traits and fitness in the RIL population with path analysis. To examine the effects of differences in dormancy on the relative fitness of the two parental genotypes, we planted dormant seeds during the seed dispersal period and non-dormant seeds during the germination period of the local population. Key Results In the RIL population, strong primary dormancy was associated with high seedling survival, but with low adult survival and fecundity, and path analysis indicated that this could be explained by effects on germination timing, rosette size and flowering start. The relationship between primary seed dormancy and germination proportion varied among years, and this was associated with differences in seasonal changes in soil moisture. The planting of dormant and non-dormant seeds indicated that the lower primary dormancy of the local Swedish genotype contributed to its higher germination proportion in two years and to its higher fecundity in one year. Conclusions Our results show that seed dormancy affects trait expression and fitness components across the life cycle, and suggest that among-year variation in the incidence of drought during the germination period should be considered when predicting the consequences of climatic change for population growth and evolution

Data from: Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana

The genetic basis of seed dormancy, a key life-history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions

QTLanalysis

Script for QTL mapping in

Parents_phenotypes

This file contains data on establishment success, adult survival, fecundity, fitness (number of fruits per planted viable seed), and mean germination time of seedling in plugs planted with the parental genotypes (Italian or Swedish) in the 2012, 2013 and 2014 experiments in Sweden