Low-Grade Endometrial Stromal Sarcoma - a Review

Like other uterine sarcomas, low-grade endometrial stromal sarcomas (LG-ESS) are a very rare tumor entity. In the past, research studies therefore discussed the various different types of the disease in combination. In addition, the classification of endometrial stromal tumors presented difficulties for quite some time so that in earlier studies it was not always possible to precisely distinguish between LG-ESS, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. For LG-ESS, surgery with hysterectomy and adnexectomy is the first-line treatment. The benefits of lymphadenectomy and tumor debulking are unclear. Endocrine therapy with gestagens and aromatase inhibitors is under discussion to provide adjuvant treatment for patients with advanced stages of the disease. As radiotherapy only provides locoregional control, and in view of the usually good prognosis of patients with LG-ESS, its benefits need to be weighed against its side effects. In the case of recurrence, repeat surgery is the first choice. Further research studies viewing LG-ESS as a distinct entity are needed in order to improve treatment options for patients with LG-ESS

Low-Grade Endometrial Stromal Sarcoma - a Review

Like other uterine sarcomas, low-grade endometrial stromal sarcomas (LG-ESS) are a very rare tumor entity. In the past, research studies therefore discussed the various different types of the disease in combination. In addition, the classification of endometrial stromal tumors presented difficulties for quite some time so that in earlier studies it was not always possible to precisely distinguish between LG-ESS, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. For LG-ESS, surgery with hysterectomy and adnexectomy is the first-line treatment. The benefits of lymphadenectomy and tumor debulking are unclear. Endocrine therapy with gestagens and aromatase inhibitors is under discussion to provide adjuvant treatment for patients with advanced stages of the disease. As radiotherapy only provides locoregional control, and in view of the usually good prognosis of patients with LG-ESS, its benefits need to be weighed against its side effects. In the case of recurrence, repeat surgery is the first choice. Further research studies viewing LG-ESS as a distinct entity are needed in order to improve treatment options for patients with LG-ESS

Functional analyses of Pericentrin and Syne-2/Nesprin-2 interaction in ciliogenesis

Pericentrin (Pcnt) is a multifunctional scaffold protein and mutations in the human PCNT gene are associated with several diseases, including ciliopathies. Pcnt plays a crucial role in ciliary development in olfactory receptor neurons, but its function in the photoreceptor-connecting cilium is unknown. We downregulated Pcnt in the retina ex vivo and in vivo via a virus-based RNA interference approach to study Pcnt function in photoreceptors. ShRNA-mediated knockdown of Pcnt impaired the development of the connecting cilium and the outer segment of photoreceptors, and caused a nuclear migration defect. In protein interaction screens, we found that the outer nuclear membrane protein Syne-2 (also known as Nesprin-2) is an interaction partner of Pcnt in photoreceptors. Syne-2 is important for positioning murine photoreceptor cell nuclei and for centrosomal migration during early ciliogenesis. CRISPR/Cas9-mediated knockout of Syne-2 in cell culture led to an overexpression and mislocalization of Pcnt and to ciliogenesis defects. Our findings suggest that the Pcnt–Syne-2 complex is important for ciliogenesis and outer segment formation during retinal development and plays a role in nuclear migration

Knowledge and attitudes regarding medical research studies among patients with breast cancer and gynecological diseases

Background Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients’ point of view. Methods The study included 2546 patients (breast cancer 21.6 %, gynecological cancer 8.3 %, obstetrics 32.7 %, endometriosis 7.8 %, fertility treatment 3.2 %, other benign gynecological illnesses 19.2 %, no information for 7.2 %) in the outpatient clinic (45.2 %) and in the in-patient sector (54.8 %) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital’s quality management system. Results As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6 %), but only a few were also willing to take part in them (58.4 %). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians. Conclusions The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences

<p>Abstract</p> <p>Background</p> <p>In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year.</p> <p>Methods</p> <p>Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses.</p> <p>Results</p> <p>DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up.</p> <p>Conclusions</p> <p>In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found.</p

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Seeing Polycentrically: Examining Governance Situations Using a Polycentricity Lens

Because many types of governance can be polycentric, an observer faces a challenge in trying to identify and understand polycentric governance in actual settings. This chapter adopts the perspective of thinking about polycentricity as a lens through which to view governance situations. We take an inquiry approach, considering how one might determine whether and in what ways a given governance situation demonstrates the characteristics of polycentric governance. We proceed through a series of questions an observer could pose as part of 'seeing polycentrically', i.e., looking at the aspects and dimensions of polycentric governance introduced in Stephan, Marshall, and McGinnis as a way of building an understanding of a governance situation. We attempt to describe why these queries are important and how posing and answering these questions helps in examining and understanding the situation. We close the chapter by considering the challenges of assessing the operation of polycentric governance arrangements

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe