Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn study

AIMS/HYPOTHESIS: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. METHODS: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45 degrees fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. RESULTS: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. CONCLUSIONS/INTERPRETATION: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopath

Uniaxial Phase Transition in Si : Ab initio Calculations

Based on a previously proposed thermodynamic analysis, we study the relative stabilities of five Si phases under uniaxial compression using ab initio methods. The five phases are diamond, beta-tin, sh, sc, and hcp structures. The possible phase-transition patterns were investigated by considering the phase transitions between any two chosen phases of the five phases. By analyzing the different conributions to the relative pahse stability, we identified the most important factors in reducing the phase-transition pressures at uniaxial compression. We also show that it is possible to have phase transitions occur only when the phases are under uniaxial compression, in spite of no phase transition when under hydrostatic commpression. Taking all five phases into consideration, the phase diagram at uniaxial compression was constructed for pressures under 20 GPa. The stable phases were found to be diamond, beta-tin and sh structures, i.e. the same as those when under hydrostatic condition. According to the phase diagram, direct phase transition from the diamond to the sh phase is possible if the applied uniaxial pressures, on increasing, satisfy the condition of Px>Pz. Simiilarly, the sh-to-beta-tin transition on increeasing pressures is also possible if the applied uniaxial pressures are varied from the condition of Px>Pz, on which the phase of sh is stable, to that of Px<Pz, on which the beta-tin is stable

EMDR for children with medically related subthreshold PTSD: short-term effects on PTSD, blood-injection-injury phobia, depression and sleep

Background: Paediatric illness, injury and medical procedures are potentially traumatic experiences with a range of possible negative psychosocial consequences. To prevent psychosocial impairment and improve medical adherence, evidence-based psychotherapy should be offered if indicated. Eye movement desensitization and reprocessing (EMDR) has been found to reduce symptoms of posttraumatic stress disorder (PTSD) in adults. The evidence for the use with children is promising. Furthermore, recent studies indicate its effectiveness for the treatment of other psychological symptomatology. However, the effectiveness of EMDR in children with subthreshold PTSD after medically related trauma has not yet been investigated. Objective: Investigating the short-term effectiveness of EMDR on posttraumatic stress, anxiety, depression and sleep problems in children with subthreshold PTSD after hospitalization through a randomized controlled trial (RCT). Method: Following baseline screening of 420 children from various Dutch hospitals, 74 children (4–15 years old) with medically related subthreshold PTSD were randomized to EMDR (n = 37) or care-as-usual (CAU; n = 37). Follow-up assessment took place after M = 9.7 weeks. Generalized Estimating Equation (GEE) analyses were performed to examine the effectiveness of EMDR compared to CAU. Results: Children in both groups improved significantly over time on all outcomes. However, the EMDR group improved significantly more as to child-reported symptoms of blood-injection-injury (BII) phobia and depression, and child-, and parent-reported sleep problems of the child. There was no superior effect of EMDR compared to CAU on subthreshold PTSD symptom reduction. Conclusions: EMDR did not perform better than CAU in reducing PTSD symptoms in a paediatric sample of children with subthreshold PTSD after hospitalization. However, the study results indicate that EMDR might be superior in reducing symptoms of blood-injection-injury phobia, depression and sleep problems

Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene

Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, P(meta)=2.15 × 10(−09)), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10(−06)), and further show it is an eQTL for FNDC1 (P=9.3 × 10(−05)). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM

Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Identifying distinct trajectories of acute otitis media in children: A prospective cohort study

Objectives: To identify possibly distinct acute otitis media (AOM) trajectories in childhood and identify determinants associated with specific AOM trajectories. To explore which child will become prone to recurrent AOM episodes and which will not. Des

Eye movement desensitization and reprocessing (EMDR) in children and adolescents with subthreshold PTSD after medically related trauma: design of a randomized controlled trial.

Background: Three in every 10 children and adolescents admitted to a hospital or undergoing medical treatment develop subthreshold symptoms of posttraumatic stress disorder (PTSD). When untreated, subthreshold PTSD can have a serious impact on psychosocial functioning, quality of life and long-term psychopathology. However, research investigating subthreshold PTSD and its treatment following paediatric medical interventions and/or hospitalization is scarce. Eye Movement Desensitization and Reprocessing (EMDR) is a fast and non-invasive psychosocial treatment for posttraumatic stress complaints. However, the effectiveness of EMDR in paediatric patients with subthreshold PTSD has not previously been systematically investigated. Objective: Describing the design of a randomized controlled trial (RCT) set up to evaluate the effectiveness of EMDR in children with subthreshold PTSD after hospitalization. Method: Children aged 4–15 years who have undergone a one-time (trauma type I) or repeated (trauma type II) hospitalization up to five years ago will be included. Participating children will be first screened with a standardized questionnaire for PTSD-symptoms. Subsequently, children with subthreshold PTSD will be randomly assigned to (1) approximately six sessions of standardized EMDR or (2) care as usual (CAU). Children with full diagnostic PTSD do not participate in the RCT, but are referred for direct treatment. Follow-up measurements will take place after eight weeks and eight months. Discussion: Considering the scarce evidence for the effectiveness of EMDR in children with medically related trauma, clinicans, researchers and children treated in hospitals can benefit from this study. Potential strengths and limitations of this study are discussed. Trial Registration: Netherlands Trial Register NTR580