Induction of Cell Stress in Neurons from Transgenic Mice Expressing Yellow Fluorescent Protein: Implications for Neurodegeneration Research

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Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci.

Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation and 1p/19q co-deletion. These data allowed definition of five molecular subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild-type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple-negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only (TERT promoter mutated, IDH wild-type, 1p/19q wild-type). Most glioma risk loci showed subtype specificity: (1) the 8q24.21 SNP for triple-positive glioma; (2) 5p15.33, 9p21.3, 17p13.1 and 20q13.33 SNPs for TERT-only glioma; (3) 1q44, 2q33.3, 3p14.1, 11q21, 11q23.3, 14q12, and 15q24.2 SNPs for IDH mutated glioma. To link risk SNPs to target candidate genes we analysed Hi-C and gene expression data, highlighting the potential role of IDH1 at 2q33.3, MYC at 8q24.21 and STMN3 at 20q13.33. Our observations provide further insight into the nature of susceptibility to glioma

Parents' psychological adjustment in families of children with Spina Bifida: a meta-analysis

BACKGROUND: Spina Bifida (SB) is the second most common birth defect worldwide. Since the chances of survival in children with severe SB-forms have increased, medical care has shifted its emphasis from life-saving interventions to fostering the quality of life for these children and their families. Little is known, however, about the impact of SB on family adjustment. Reviewers have struggled to synthesize the few contradictory studies available. In this systematic review a new attempt was made to summarize the findings by using meta-analysis and by delimiting the scope of review to one concept of family adjustment: Parents' psychological adjustment. The questions addressed were: (a) do parents of children with SB have more psychological distress than controls? (b) do mothers and fathers differ? and (c) which factors correlate with variations in psychological adjustment? METHODS: PsycInfo, Medline, and reference lists were scanned. Thirty-three relevant studies were identified of which 15 were eligible for meta-analysis. RESULTS: SB had a negative medium-large effect on parents' psychological adjustment. The effect was more heterogeneous for mothers than for fathers. In the reviewed studies child factors (age, conduct problems, emotional problems, and mental retardation), parent factors (SES, hope, appraised stress, coping, and parenting competence), family factors (family income, partner relationship, and family climate), and environmental factors (social support) were found to be associated with variations in parents' psychological adjustment. CONCLUSION: Meta-analysis proved to be helpful in organizing studies. Clinical implications indicate a need to be especially alert to psychological suffering in mothers of children with SB. Future research should increase sample sizes through multi-center collaborations

Feasibility, safety and cost-effectiveness of transjugular liver biopsy following major surgery in patients with haemophilia.

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of patients with haemophilia became infected with the hepatitis C virus. Although transjugular liver biopsy can be safely performed in these patients, the procedure is associated with a significant financial burden mainly related to replacement therapy with clotting factor. The purpose of this study was to evaluate the feasibility and safety of transjugular liver biopsy in patients with haemophilia substituted with clotting factor concentrates for major surgical procedures. Over the last 5 years, transjugular liver biopsy was performed in nine patients with haemophilia within 1-10 days after orthopaedic (7), thoracic (1) or abdominal surgery (1). All patients had abnormal liver function tests and persistent hepatitis C viraemia. At the time of the biopsy, patients received recombinant factor VIII delivered by dose-adjusted continuous infusion through a central catheter inserted preoperatively in the left internal jugular (n = 8) or in an ante-cubital vein (n = 1). Before the biopsy, basal FVIII levels were raised to 80-100% by a bolus infusion and maintained above 80% for 24 h. The biopsy was informative in all cases. Only one patient developed an episode of supraventricular dysrhythmia. No bleeding or infectious complications were observed. When compared with elective liver biopsy performed outside the postsurgical period, the cost-savings per biopsy were 19 875 +/- 2660 euro. This study shows that intensive replacement therapy required by surgical procedures provides a safe and cost-effective opportunity for transjugular liver biopsy in patients with haemophilia and active hepatitis C

Development of an animal model of autoimmune thyroid eye disease.

In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we have examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroiditis with considerable follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in controls. None of the NOD animals developed any orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the receptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose tissue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital changes or thyroiditis were observed in control BALB/c mice. We have induced orbital pathology having many parallels with human TED, only in BALB/c mice, suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for the development of TED.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe