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Abstract Background Extremely preterm infants, defined as those born before 28 weeks’ gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. Methods The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. Discussion Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. Trial registration ( Clinicaltrials.gov ): NCT05604846

Abstract: Introduction: “School engagement” refers to the feelings and thoughts pupils have for school, which, according to theory, can be divided into behavioral, cognitive, and emotional engagement. Previously identified factors predicting school engagement are teacher-student relationship, individual characteristics, emotional stability, and gender. Aim: The current study addresses changes in behavioral, cognitive, and emotional school engagement during the COVID-19 pandemic. It analyzes the effect of previously identified risk factors on self-reported change in school engagement among middle-school students in Finland. Methods: We collected the data in the spring of 2021. Participants were 1,788 Finnish middle-school pupils (age range 12–17) who responded to an online survey during the school day. Results: After we controlled for multiple tests, the results revealed a few significant factors associated with negative changes in school engagement. However, prior anxiety, depression, or externalizing behavior were related to negative changes. Discussion: Pupils with previous risk factors for low engagement or different kinds of struggles in school were more likely to react negatively to the changes brought forth by the pandemic on several engagement outcomes compared to students with few or no risk factors. In the future, should disruptions of normal school routines be necessary, special attention should be given to planning proper support for at-risk students.

There has been a noticeable decline in life satisfaction among adolescents globally in recent years. The present study explored the immediate and long-term effects of a positive psychology intervention course, Study with Strength, on the well-being of students at general upper secondary school in Finland during the pandemic. Based on a partly randomized wait-list control group design, the study included a final sample of 350 students from 10 schools. Self-report measures were used to assess both immediate between-group effects and long-term within-group effects of the intervention on student well-and ill-being. A combination of methods from positive psychology and cognitive therapy were applied, and the course was administered by the participating schools’ own teachers and student-welfare personnel. The findings show that the Study with Strength intervention course enhanced the students’ experiences of positive practices at school, happiness and of positive emotions. However, the effect sizes were small. The intervention did not have any immediate effects on all aspects of well-being, negative emotions, depression, or study-related burnout. The significant, positive changes in students’ well-being in the analysis of long-term effects must be interpreted with caution. The students also reported a positive effect of the intervention both on their personal lives and in their studies. Overall, it appears that the intervention had a small but positive impact, nudging students towards enhanced well-being. The results offer valuable insights into the implementation of positive education on students at general upper secondary school aged 15–19.

Abstract Aims In heart failure with preserved ejection fraction (HFpEF), regional heterogeneity of clinical phenotypes is increasingly recognized, with coronary microvascular dysfunction (CMD) potentially being a common shared feature. We sought to determine the regional differences in clinical characteristics and prevalence of CMD in HFpEF. Methods and results We analysed clinical characteristics and CMD in 202 patients with stable HFpEF (left ventricular ejection fraction ≥40%) in Finland, Singapore, Sweden, and United States in the multicentre PROMIS‐HFpEF study. Patients with unrevascularized macrovascular coronary artery disease were excluded. CMD was assessed using Doppler echocardiography and defined as coronary flow reserve (adenosine‐induced vs. resting flow)

Abstract Background The glycinergic system plays an important inhibitory role in the mouse central nervous system, where glycine controls the excitability of spinal itch- and pain-mediating neurons. Impairments of the glycine receptors can cause motor and sensory deficits. Glycine exerts inhibition through interaction with ligand-gated ion channels composed of alpha and beta subunits. We have investigated the mRNA expression of the glycine receptor alpha 3 (Glra3) subunit in the nervous system as well as in several peripheral organs of female and male mice. Results Single-cell RNA sequencing (scRNA-seq) data analysis on the Zeisel et al. (2018) dataset indicated widespread but low expression of Glra3 in vesicular glutamate transporter 2 (Vglut2, Slc17a6) positive and vesicular inhibitory amino acid transporter (Viaat, Slc32a1)positive neurons of the mouse central nervous system. Highest occurrence of Glra3 expression was identified in the cortex, amygdala, and striatal regions, as well as in the hypothalamus, brainstem and spinal cord. Bulk quantitative real-time-PCR (qRT-PCR) analysis demonstrated Glra3 expression in cortex, amygdala, striatum, hypothalamus, thalamus, pituitary gland, hippocampus, cerebellum, brainstem, and spinal cord. Additionally, male mice expressed higher levels of Glra3 in all investigated brain areas compared with female mice. Lastly, RNAscope spatially validated Glra3 expression in the areas indicated by the single-cell and bulk analyses. Moreover, RNAscope analysis confirmed co-localization of Glra3 with Slc17a6 or Slc32a1 in the central nervous system areas suggested from the single-cell data. Conclusions Glra3 expression is low but widespread in the mouse central nervous system. Clear sex-dependent differences have been identified, indicating higher levels of Glra3 in several telencephalic and diencephalic areas, as well as in cerebellum and brainstem, in male mice compared with female mice.

Abstract Background Non-communicable diseases such as cardiovascular conditions and diabetes are rising in sub-Saharan Africa. Prevention strategies to mitigate non-communicable diseases include improving diet, physical activity, early diagnosis, and long-term management. Early identification of individuals at risk based on risk-score models – such as the Framingham Risk Score (FRS) for 10-year risk of cardiovascular disease and the Finnish type 2 Diabetes risk score (FINDRISC) for type 2 diabetes which are used in high-income settings – have not been well assessed in sub-Saharan Africa. The purpose of this study was to qualitatively assess local knowledge of components of these risk scores in a rural Ugandan setting. Methods Semi-structured qualitative in-depth interviews were conducted with a purposively selected sample of 15 participants who had responded to the FRS and FINDRISC questionnaires and procedures embedded in the Rakai Community Cohort Study. Data were summarized and categorized using content analysis, with support of Atlas.ti. Results Participants described local terms for hypertension (“pulessa”) and type 2 diabetes (“sukaali”). Most participants understood physical activity as leisure physical activity, but when probed would also include physical activity linked to routine farm work. Vegetables were typically described as "plants", “leafy greens”, and “side dish”. Vegetable and fruit consumption was described as varying seasonally, with peak availability in December after the rainy season. Participants perceived themselves to have good knowledge about their family members’ history of type 2 diabetes and hypertension. Conclusions While most items of the FRS and FINDRISC were generally well understood, physical activity needs further clarification. It is important to consider the seasonality of fruits and vegetables, especially in rural resource-poor settings. Current risk scores will need to be locally adapted to estimate the 10-year risk of cardiovascular diseases and type 2 diabetes in this setting.

The 2021 World Health Organization (WHO) grading system of isocitrate dehydrogenase (IDH)‐mutant astrocytomas relies on histological features and the presence of homozygous deletion of the cyclin‐dependent kinase inhibitor 2A and 2B (CDKN2A/B). DNA methylation profiling has become highly relevant in the diagnosis of central nervous system (CNS) tumors including gliomas, and it has been incorporated into routine clinical diagnostics in some countries. In this study, we, therefore, examined the value of DNA methylation‐based classification for prognostication of patients with IDH‐mutant astrocytomas. We analyzed histopathological diagnoses, genome‐wide DNA methylation array data, and chromosomal copy number alteration profiles from a cohort of 385 adult‐type IDH‐mutant astrocytomas, including a local cohort of 127 cases and 258 cases from public repositories. Prognosis based on WHO 2021 CNS criteria (histological grade and CDKN2A/B homozygous deletion status), other relevant chromosomal/gene alterations in IDH‐mutant astrocytomas and DNA methylation‐based subclassification according to the molecular neuropathology classifier were assessed. We demonstrate that DNA methylation‐based classification of IDH‐mutant astrocytomas can be used to predict outcome of the patients equally well as WHO 2021 CNS criteria. In addition, methylation‐based subclassification enabled the identification of IDH‐mutant astrocytoma patients with poor survival among patients with grade 3 tumors and patients with grade 4 tumors with a more favorable outcome. In conclusion, DNA methylation‐based subclassification adds prognostic information for IDH‐mutant astrocytomas that can further refine the current WHO 2021 grading scheme for these patients. [ABSTRACT FROM AUTHOR]