Helsen C.,Molecular Endocrinology Laboratory |
Kerkhofs S.,Molecular Endocrinology Laboratory |
Clinckemalie L.,Molecular Endocrinology Laboratory |
Spans L.,Molecular Endocrinology Laboratory |
And 4 more authors.
Molecular and Cellular Endocrinology
The gene family of nuclear receptors is characterized by the presence of a typical, well conserved DNA-binding domain. In general, two zinc coordinating modules are folded such that an α-helix is inserted in the major groove of the DNA-helix displaying a sequence similar to one of two hexameric consensus motifs. Both zinc molecules coordinate four cysteines. Although the DNA-binding domains as well as the hormone response elements are very similar, each nuclear receptor will affect transcription of a specific set of target genes. This is in part due to some important receptor-specific variations on the general theme of DNA interaction.For most nuclear receptors, the DNA-binding domain dimerizes on DNA, which explains why most hormone response elements consist of a repeat of two hexamers. The hexamer dimers can be organized either as direct, inverted or everted repeats with spacers of varying lengths. The DNA can be bound by homodimers, heterodimers and for some orphan receptors, as monomer.Another key element for DNA binding by nuclear receptors is the carboxy-terminal extension of the DNA-binding domain extending into the hinge region. This part not only co-determines sequence specificity, but also affects other functions of the receptors like nuclear translocation, intranuclear mobility and transactivation potential. Moreover, allosteric signals passing through towards other receptor domains, explain why to some extent, the DNA elements can also be considered as controlling ligands. © 2011 Elsevier Ireland Ltd. Source
Dunselman G.A.J.,Maastricht University |
Vermeulen N.,European Society of Human Reproduction and Embryology |
Becker C.,University of Oxford |
Calhaz-Jorge C.,University of Lisbon |
And 10 more authors.
STUDY QUESTIONWhat is the optimal management of women with endometriosis based on the best available evidence in the literature?SUMMARY ANSWERUsing the structured methodology of the Manual for ESHRE Guideline Development, 83 recommendations were formulated that answered the 22 key questions on optimal management of women with endometriosis.WHAT IS KNOWN ALREADYThe European Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis and treatment of endometriosis (2005) has been a reference point for best clinical care in endometriosis for years, but this guideline was in need of updating.STUDY DESIGN, SIZE, DURATIONThis guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline.PARTICIPANTS/MATERIALS, SETTING, METHODSNA.MAIN RESULTS AND THE ROLE OF CHANCEThe guideline provides 83 recommendations on diagnosis of endometriosis and on the treatment of endometriosis-associated pain and infertility, on the management of women in whom the disease is found incidentally (without pain or infertility), on prevention of recurrence of disease and/or painful symptoms, on treatment of menopausal symptoms in patients with a history of endometriosis and on the possible association of endometriosis and malignancy.LIMITATIONS, REASONS FOR CAUTIONWe identified several areas in care of women with endometriosis for which robust evidence is lacking. These areas were addressed by formulating good practice points (GPP), based on the expert opinion of the guideline group members.WIDER IMPLICATIONS OF THE FINDINGSSince 32 out of the 83 recommendations for the management of women with endometriosis could not be based on high level evidence and therefore were GPP, the guideline group formulated research recommendations to guide future research with the aim of increasing the body of evidence. © 2014 The Author. Source
Van Moerkercke W.,University Hospitals Leuven |
Verhamme M.,Herestraat |
Doubel P.,University Hospitals Leuven |
Meeus G.,University Hospitals Leuven |
And 2 more authors.
Acta Gastro-Enterologica Belgica
In a review of the literature concerning autoimmune pancreatitis we had special interest for the concept of IgG4-related pa - thology as a systemic disease with several clinical manifestations. In general, IgG4-positivity can not only be found in the pancreas, but also at the level of the kidneys, extrahepatic biliary ducts, gallbladder, lungs, salivary glands, lacrimal glands, retroperitoneal tissue, ureters, prostate, meninges and lymph nodes. IgG4 seems to be a central key player in the pathophysiology of this disease. Source
Vriesendorp P.A.,Erasmus University Rotterdam |
Schinkel A.F.L.,Erasmus University Rotterdam |
Van Cleemput J.,Herestraat |
Willems R.,Herestraat |
And 6 more authors.
American Heart Journal
Background Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM), but this can be prevented by an implantable cardioverter-defibrillator (ICD). The aim of this study is to evaluate HCM patients with ICDs for primary or secondary prevention of SCD. Methods The study population consisted of all HCM patients with an ICD in 2 tertiary referral clinics. End points during follow-up were total and cardiac mortality, appropriate and inappropriate ICD intervention, and device-related complications. Cox-regression analysis was performed to identify predictors of outcome. Results ICDs were implanted in 134 patients with HCM (mean age 44 ± 17 years, 34% women, 4.2 ± 4.8 years follow-up). Annualized cardiac mortality rate was 3.4% per year and associated with New York Heart Association class III or IV (HR 5.2 [2.0-14, P =.002]) and cardiac resynchronization therapy (HR 6.3 [2.1-20, P =.02]). Appropriate ICD interventions occurred in 38 patients (6.8%/year) and was associated with implantation for secondary prevention of SCD (HR 4.0 [1.8-9.1], P =.001) and male gender (HR 3.3 [1.2-9.0], P =.02). Inappropriate ICD intervention occurred in 21 patients (3.7%/year) and in 20 patients device related complications were documented (3.6%/year). Conclusion ICDs successfully abort life-threatening arrhythmias in HCM patients at increased risk of SCD with an annualized intervention rate of 6.8% per year. End-stage heart failure is the main cause of mortality in these patients. The annualized rate of inappropriate ICD intervention was 3.7% per year, whereas device-related complications occurred 3.6% per year. © 2013 Mosby, Inc. Source
Hermans H.,Herestraat |
Vanassche T.,Herestraat |
Herijgers P.,Catholic University of Leuven |
Meuris B.,Catholic University of Leuven |
And 3 more authors.
Cardiology in Review
Heart valve prostheses carry a risk for thrombosis and require an antithrombotic strategy to prevent stroke, systemic embolism, and prosthetic valve thrombosis. Contemporary randomized trials to guide the clinician on the optimal anticoagulant treatment are scarce, and the validity of the historical data for current recommendations can be questioned in view of the changes in valve prostheses, the patient population, and antithrombotic therapies. This limited evidence from clinical trials translates into divergent recommendations from the different scientific societies on the optimal intensity of oral anticoagulation and on the indication for antiplatelet therapy. The availability of new antithrombotic agents and the unclear thrombotic risk of the currently used prostheses underscore the need to redefine antithrombotic treatment in patients with heart valve prostheses. Copyright © 2012 Lippincott Williams & Wilkins. Source