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Previous research indicates worse outcomes for children and young people in out-of-home care compared to their peers. To improve the quality of current residential care, research is needed to deepen our understanding of the key factors and mechanisms that explain the effectiveness of residential care on child level. The aim of this study is to evaluate the short-term (i.e., during care) effectiveness of residential care as a child welfare intervention by different service providers. The study includes two pre-specified primary child-level outcomes 1) psychosocial functioning, assessed through the Strengths and Difficulties Questionnaires (SDQ) including both total difficulties scores and subscales and 2) attainment of individual goals of the child. Secondary outcome measures include improved experiences of emotional warmth and safety (CEWSS-A). Further associations between key characteristics of the residential care unit, the child and outcomes are assessed. The data consist of longitudinal survey data collected from 12-17-year-old children and staff in a total sample of public and private residential care units offering specialized care in three wellbeing services countries in Finland. The baseline (T0) data is collected between 1.4.2025-31.8.2026 with a follow up of 6 and 12 months for each child (T1 and T2). The data is primarily analysed with linear mixed models. Findings explore the short-term effectiveness and change mechanisms of residential care as \"service as usual\" to understand how it should be organised and produced to improve its ability to meet aims during care. The study design embraces the complexity and changeability on different levels of the residential care setting.

Dehydrins are intrinsically disordered plant proteins whose expression is upregulated under conditions of desiccation and cold stress. Their molecular function in ensuring plant survival is not yet known, but several studies suggest their involvement in membrane stabilization. The dehydrins are characterized by a broad repertoire of conserved and repetitive sequences, out of which the archetypical K-segment has been implicated in membrane binding. To elucidate the molecular mechanism of these K-segments, we examined the interaction between lipid membranes and a dehydrin with a basic functional sequence composition: Lti30, comprising only K-segments. Our results show that Lti30 interacts electrostatically with vesicles of both zwitterionic (phosphatidyl choline) and negatively charged phospholipids (phosphatidyl glycerol, phosphatidyl serine, and phosphatidic acid) with a stronger binding to membranes with high negative surface potential. The membrane interaction lowers the temperature of the main lipid phase transition, consistent with Lti30' s proposed role in cold tolerance. Moreover, the membrane binding promotes the assembly of lipid vesicles into large and easily distinguishable aggregates. Using these aggregates as binding markers, we identify three factors that regulate the lipid interaction of Lti30 in vitro: (1) a pH dependent His on/off switch, (2) phosphorylation by protein kinase C, and (3) reversal of membrane binding by proteolytic digest.

Abstract Context Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. Objective To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. Design, Setting and Participants A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. Main Outcome Measures We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. Results Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. Conclusions This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

ObjectiveThe Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Media multitasking is an increasingly prominent behavior in affluent societies. However, it still needs to be established if simultaneous use of several modes of media content has an influence on higher cognitive functions, such as divided attention. In this study, attention shifting was the primary focus, since switching between tasks is assumed to be necessary for media multitasking. Two tasks, the number–letter and local–global task, were used as measures of switching ability. The cognitive reflections task was included to control for possible effects of intelligence. Results from linear regression analyses showed that higher levels of media multitasking was related to lower switching costs in the two attention-shifting tasks. These findings replicate previous findings suggesting that heavy media multitaskers perform better on select measures of task switching. We suggest two possible explanations for our results: media multitasking may practice skills needed for switching between tasks, or high media multitaskers are choosing this style of technology use due to a dominating personality trait in this group.

The dehydrins are a class of drought-induced proteins in plants that lack a fixed three-dimensional structure. Their specific molecular action, as well as the reason for their disordered character, is as yet poorly understood. It has been speculated, however, that the dehydrins are tuned to acquire a biologically active structure only under the conditions in which they normally function (i.e. upon dehydration). To test this hypothesis, we here investigate the effect of reduced water content and macromolecular crowding on three dehydrins from Arabidopsis (Arabidopsis thaliana). As a simplistic model for mimicking cellular dehydration, we used polyethylene glycol, glycerol, and sugars that plants naturally employ as compatible solutes (i.e. sucrose and glucose). Macromolecular crowding was induced by the large polysaccharides Ficoll and dextran. The results show that the dehydrins are remarkably stable in their disordered state and are only modestly affected by the solvent alterations. A notable exception is the dehydrin Cor47, which shows a small, intrinsic increase in helical structure at high concentrations of osmolytes. We also examined the effect of phosphorylation but found no evidence that such posttranslational modifications of the dehydrin sequences modulate their structural response to osmolytes and crowding agents. These results suggest that the dehydrins are highly specialized proteins that have evolved to maintain their disordered character under conditions in which unfolded states of several globular proteins would tend to collapse.

Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10−5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10−8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05–2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.

Purpose The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [ 18 F]THK5317 (also known as (S) -[ 18 F]THK5117) retention in different stages of Alzheimer’s disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. Methods Thirty-three individuals were enrolled, including nine patients with Alzheimer’s disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer’s disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [ 18 F]THK5317, [ 11 C] Pittsburgh compound B ([ 11 C]PIB), and [ 18 F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [ 11 C]PIB-positive ( n  = 11) and MCI [ 11 C]PIB-negative ( n  = 2) groups. Results Test-retest variability for [ 18 F]THK5317-PET was very low (1.17–3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [ 11 C]PIB-positive) and dementia-stage Alzheimer’s disease had significantly higher [ 18 F]THK5317 retention than healthy controls ( p  = 0.002 and p  = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [ 18 F]THK5317 retention and [ 18 F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [ 18 F]THK5317 and [ 11 C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [ 11 C]PIB but high [ 18 F]THK5317 retentions with a different regional distribution from that in Alzheimer’s disease patients. Conclusions The tau-specific PET tracer [ 18 F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

Lifestyle interventions affect patients' risk factors for metabolic syndrome (MeSy), a pre-stage to cardiovascular diseases, diabetes and related complications. An effective lifestyle intervention is the Swedish Björknäs intervention, a 3-year randomized controlled trial in primary care for MeSy patients. To include future disease-related cost and health consequences in a cost-effectiveness analysis, a simulation model was used to estimate the short-term (3-year) and long-term (lifelong) cost-effectiveness of the Björknäs study. A Markov micro-simulation model was used to predict the cost and quality-adjusted life years (QALYs) for MeSy-related diseases based on ten risk factors. Model inputs were levels of individual risk factors at baseline and at the third year. The model estimated short-term and long-term costs and QALYs for the intervention and control groups. The cost-effectiveness of the intervention was assessed using differences-in-differences approach to compare the changes between the groups in the health care and societal perspectives, using a 3% discount rate. A 95% confidence interval (CI), based on bootstrapping, and sensitivity analyses describe the uncertainty in the estimates. In the short-term, costs are predicted to increase over time in both groups, but less in the intervention group, resulting in an average cost saving/reduction of US$-700 (in 2012, US$1=six point five seven SEK) and US$-500, in the societal and health care perspectives. The long-term estimate also predicts increased costs, but considerably less in the intervention group: US$-7,300 (95% CI: US$-19,700 to US$-1,000) in the societal, and US$-1,500 (95% CI: US$-5,400 to US$2,650) in the health care perspective. As intervention costs were US$211 per participant, the intervention would result in cost saving. Furthermore, in the long-term an estimated 0.46 QALYs (95% CI: 0.12 to 0.69) per participant would be gained. The Swedish Björknäs study appears to reduce demands on societal and health care resources and increase health-related quality of life.

Background As the survival rate of preterm infants continues to rise worldwide, more infants are at risk of developing sight-threatening retinopathy of prematurity (ROP). Destructive retinal laser treatment and intravitreal injections of anti-vascular endothelial growth factor (VEGF), factor, which have potential systemic side effects, are necessary to prevent blindness in severe cases of ROP. Off-label use in clinical settings suggests that dexamethasone eye drops, 1 mg/ml, may prevent the progression of ROP to severe disease (Type 1 ROP) requiring treatment. Our current study aims to assess the efficacy and safety of timely administered dexamethasone eye drops to reduce the need for laser or anti-VEGF ROP treatment in preterm infants. Methods In a randomized prospective interventional, multi-centre, double-blinded trial, we plan to include 100 infants with severe ROP born before gestational age 30 weeks in Sweden. Infants will be randomized to intervention with dexamethasone eye drops (1 mg/ml) (n  = 50) or placebo, saline ( n  = 50) until either ROP is resolved or severe ROP (Type 1 ROP) development occurs, fulfilling ROP treatment criteria. Eye drops will be administered one drop per day or every other day, depending on the severity of ROP, with a maximum duration of 12 weeks. The primary objective is to evaluate whether dexamethasone intervention reduces the proportion of infants developing Type 1 ROP compared to infants receiving a placebo. Adverse events and potential side effects will be recorded, such as high intraocular pressure and growth restriction. Levels of cortisol in saliva and glucose in urine will be measured repeatedly. Secondary outcomes will include the timing of ROP progression, the recurrence rate after ROP treatment and retinal morphology. An ophthalmological follow-up will be initiated at 2 and 5.5 years of age, evaluating visual acuity, refractive errors, strabismus, retinal morphology and ophthalmological complications. All outcomes in the study will be compared between the infants receiving dexamethasone intervention and those receiving placebo. Discussion Timely administration of dexamethasone eye drops may prevent severe ROP from progressing to Type 1 ROP, which requires treatment. This study aims to assess the efficacy and safety of dexamethasone intervention to support its clinical use and national guidelines. Trial registration EudraCT, 2020–004933-19, registered in January 2021 and CTIS, 2023–505318-97–00, registered in August 2023. Clinical trial number Not applicable.