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Background: Assisted reproductive technology (ART) has been associated with increased risks for growth disturbance, disrupted imprinting as well as cardiovascular and metabolic disorders. However, the molecular mechanisms and whether they are a result of the ART procedures or the underlying subfertility are unknown., Methods: We performed genome-wide DNA methylation (EPIC Illumina microarrays) and gene expression (mRNA sequencing) analyses for a total of 80 ART and 77 control placentas. The separate analyses for placentas from different ART procedures and sexes were performed. To separate the effects of ART procedures and subfertility, 11 placentas from natural conception of subfertile couples and 12 from intrauterine insemination treatments were included., Results: Here we show that ART-associated changes in the placenta enriche in the pathways of hormonal regulation, insulin secretion, neuronal development, and vascularization. Observed decreased number of stromal cells as well as downregulated TRIM28 and NOTCH3 expressions in ART placentas indicate impaired angiogenesis and growth. DNA methylation changes in the imprinted regions and downregulation of TRIM28 suggest defective stabilization of the imprinting. Furthermore, downregulated expression of imprinted endocrine signaling molecule DLK1 associates with both ART and subfertility., Conclusions: Decreased expressions of TRIM28, NOTCH3, and DLK1 bring forth potential mechanisms for several phenotypic features associated with ART. Our results support previous procedure specific findings: the changes associated with growth and metabolism link more prominently to the fresh embryo transfer with smaller placentas and newborns, than to the frozen embryo transfer with larger placentas and newborns. Furthermore, since the observed changes associate also with subfertility, they offer a precious insight to the molecular background of infertility., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/objective: The roles of overall diet quality in linking genetic background with anthropometric measures are unclear, particularly regarding the recently developed Planetary Health Diet (PHD). This study aims to determine if the PHD mediates or moderates the relationship between genetic susceptibility to obesity and anthropometric measures., Subjects/methods: The study involved 2942 individuals from a Finnish population-based cohort (54% women, mean age 53 (SD ± 13) years). Habitual diet was assessed using a validated 130-item food frequency questionnaire, and the PHD Score (total score range 0-13 points) was adapted for Finnish food culture to evaluate diet quality. Genetic susceptibility to obesity was evaluated with a polygenic risk score (PRS) based on one million single nucleotide polymorphisms associated with body mass index (BMI). Baseline anthropometrics included weight, height, waist circumference (WC), and body fat percentage, with changes in these measures tracked over 7 years. A five-step multiple linear regression model and multivariable logistic regression with interaction terms were used to assess the mediating and moderating effects of the PHD. These analyses were also replicated in another Finnish cohort study (2 834 participants)., Results: PRS for BMI was positively associated with baseline BMI and changes in anthropometric measures, except waist circumference (p = 0.12). Significant associations were observed for baseline BMI and WC (p < 0.001), changes in BMI and WC (p = 0.01), and body fat percentage change (p = 0.05). However, the PHD (average score 3.8 points) did not mediate or moderate these relationships. These findings were consistent in the replication cohort., Conclusion: Diet quality assessed with the PHD did not mediate or moderate the associations between genetic susceptibility to obesity and anthropometric measures. This lack of effect may be partly due to low adherence to the PHD and the older age of participants ( > 50 years) at baseline., (© 2024. The Author(s).)

Minkowski space is shown to be globally stable as a solution to the massive Einstein-Vlasov system. The proof is based on a harmonic gauge in which the equations reduce to a system of quasilinear wave equations for the metric, satisfying the weak null condition, coupled to a transport equation for the Vlasov particle distribution function. Central to the proof is a collection of vector fields used to control the particle distribution function, a function of both spacetime and momentum variables. The vector fields are derived using a general procedure, are adapted to the geometry of the solution and reduce to the generators of the symmetries of Minkowski space when restricted to acting on spacetime functions. Moreover, when specialising to the case of vacuum, the proof provides a simplification of previous stability works., (© The Author(s) 2019.)

Background: Immunological studies have indicated that the effectiveness of AS03 adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix) may be of longer duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty-nine percent of children 6 months-18 years of age in Stockholm County received at least one dose of Pandemrix during the 2009 pandemic. We studied the effectiveness of the vaccine during the influenza seasons 2010-2011 and 2012-2013 in children hospitalized with virologically confirmed influenza. The season 2011-2012 was not included, since influenza A(H3N2) was the predominant circulating strain., Methods: In a retrospective case-control study using a modified test-negative design we compared the percentage vaccinated with Pandemrix among children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those diagnosed with influenza A(H3N2) or influenza B (controls) during the two seasons. We excluded children born after July 1, 2009, since only children who were 6 months of age or older received the pandemic vaccine in October-December 2009., Results: During the 2010-2011 season, 3/16 (19%) of children diagnosed with influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or influenza B had been vaccinated with Pandemrix in 2009. The odds ratio, after adjustment for sex, age and underlying diseases, for becoming a case when vaccinated with Pandemrix was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of 91.7%. During the season 2012-2013, there was no difference between the two groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with influenza A(H1N1)pdm09 had been vaccinated with Pandemrix in 2009., Conclusion: The AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix) was effective in preventing hospital admission for influenza A(H1N1)pdm09 in children during at least two seasons., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We studied the effectiveness of the AS03-adjuvanted monovalent vaccine (Pandemrix(®)) for the prevention of severe pandemic influenza A(H1N1)pdm09 in children, in 2009. All children hospitalized for influenza-like illness in Stockholm County during the peak of the pandemic were included. We compared the frequency of vaccinated children between influenza A(H1N1)pdm09 PCR positive cases and PCR negative controls in a retrospective case-control study. 95 cases and 177 controls were identified. About half of the children in both groups were between 6 months and 2 years of age. Only 1/95 (1%) cases had been vaccinated more than 14 days prior to admission, compared to 23/177 controls (13%), corresponding to a vaccine effectiveness, adjusted for co-morbid conditions, of 91% (95% confidence interval [CI] 30-99). In contrast, the risk for being a case was significantly higher among children vaccinated between 1 and 14 days prior to hospitalization, than among those who were non-vaccinated 13/95 vs. 7/177 (OR 3.6, 95% CI 1.4-9.5). We conclude that a single dose of adjuvanted vaccine was highly protective against hospitalization for influenza A(H1N1)pdm09 in children 6 month to 17 years. The reason for the increased rate of hospitalizations with confirmed influenza in children just following immunization is unclear and should be studied further., (Copyright © 2012 Elsevier Ltd. All rights reserved.)