ABSTRACT
Insomnia Disorder is the most prevalent sleep disorder, and it involves both sleep difficulties and daytime complaints. The neural underpinnings of Insomnia Disorder are poorly understood. Several existing neuroimaging studies focused on local measures and specific regions of interests, which makes it difficult to judge their whole-brain significance. We therefore here applied a data-driven approach to assess differences in whole-brain structural connectivity between adults with Insomnia Disorder and matched controls without sleep complaints. We used diffusion tensor imaging and probabilistic tractography to assess whole-brain structural connectivity, and examined group differences using network-based statistics. The results revealed a significant difference in the structural connectivity of the two groups (p = .014). Participants with Insomnia Disorder showed reduced connectivity in a sub-network that included mainly fronto-subcortical connections with the insula as a key region. By taking a whole-brain network perspective, our study enables the integration of previous inconsistent findings. Our results reveal that reduced structural connectivity of the left insula and the connections between frontal and subcortical regions are central neurobiological features of Insomnia Disorder. The importance of these areas for interoception, emotional processing, stress responses and the generation of slow-wave sleep may help guide the development of neurobiology-based models of the prevalent condition of Insomnia Disorder.
Subject(s)
Diffusion Tensor Imaging/methods , Neural Pathways/physiopathology , Sleep Initiation and Maintenance Disorders/physiopathology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Ewing's sarcoma (EWS) is a highly malignant cancer in children, adolescents and young adults. The chemotherapy required to treat female EWS patients may cause primary ovarian insufficiency and infertility as a side effect. Cryopreservation of ovarian tissue before the start of chemotherapy can potentially preserve fertility. When the patient has been cured and primary ovarian insufficiency has developed, transplantation of frozen/thawed ovarian tissue can restore ovarian function. The tissue is usually collected before chemotherapy is initiated, and malignant cells may contaminate the stored ovarian tissue, potentially causing recrudescence of the original cancer after transplantation. The risk of EWS metastasizing to the ovary is probably low but has not been studied in great detail. This review describes the available evidence on the risk of malignant cell contamination in the ovaries of EWS patients and presents a new case of malignant cells in an ovarian biopsy from a girl with EWS.
Subject(s)
Cryopreservation , Infertility, Female/etiology , Infertility, Female/therapy , Ovary/transplantation , Sarcoma, Ewing/complications , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Female , Humans , Neoplasm Recurrence, Local , Neoplasm Seeding , Ovarian Neoplasms/secondary , Radiotherapy/adverse effects , Risk , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/pathologyABSTRACT
Some women suffering from leukemia require bone marrow transplantation to be cured. Bone marrow transplantation is associated with a high risk of sterility, and some patients are offered fertility preservation by cryopreservation of the ovarian cortex. Transplantation of the ovarian cortex to women cured of leukemia who became menopausal is currently not performed because of the risk of introducing the disease. In this study, individual pieces of ovarian cortex intended for reimplantation from 25 patients with leukemia were transplanted to each of 25 nude mice for 20 weeks. The ovarian cortex was examined before and after transplantation by histology and immunohistochemistry, and RT-quantitative PCR (in the 7 patients with a known marker). Seventeen patients had the ovarian cortex retrieved when they were in complete remission. Before transplantation, 4 of 7 pieces (2 from patients in complete remission) of ovarian cortex had a positive RT-quantitative PCR. After transplantation, none of the mice revealed any sign of disease, neither in the pieces of ovarian cortex transplanted nor in any of the murine organs evaluated. Thus, the ovaries from patients in complete remission do not appear to contain viable malignant cells contrasting ovarian tissue retrieved before treatment.