Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder

Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort

Introduction: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. Methods: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. Results: During a median follow-up of 28.7 months (IQR 25.2–33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. Conclusion: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.</p

The formation and evolution of binary systems. III. Low-mass binaries in the Praesepe cluster

With the aim of investigating the binary population of the 700 Myr old Praesepe cluster, we have observed 149 G and K-type cluster members using adaptive optics. We detected 26 binary systems with an angular separation ranging from less than 0.08 to 3.3 arcsec (15-600 AU). After correcting for detection biases, we derive a binary frequency (BF) in the logP (days) range from 4.4 to 6.9 of 25.3 +/- 5.4%, which is similar to that of field G-type dwarfs (23.8%, Duquennoy & Mayor 1991). This result, complemented by similar ones obtained for the 2 Myr old star forming cluster IC 348 (Paper II) and the 120 Myr old Pleiades open cluster (Paper I), indicates that the fraction of long-period binaries does not significantly evolve over the lifetime of galactic open clusters. We compare the distribution of cluster binaries to the binary populations of star forming regions, most notably Orion and Taurus, to critically review current ideas regarding the binary formation process. We conclude that it is still unclear whether the lower binary fraction observed in young clusters compared to T associations is purely the result of the early dynamical disruption of primordial binaries in dense clusters or whether it reflects intrinsically different modes of star formation in clusters and associations. We also note that if Taurus binaries result from the dynamical decay of small-N protostellar aggregates, one would predict the existence of a yet to be found dispersed population of mostly single substellar objects in the Taurus cloud.Comment: 10 pages, 3 figure

Immunopathogenesis and Immune Modulation of Venezuelan Equine Encephalitis Virus-Induced Disease in the Mouse

AbstractThe course of Venezuelan equine encephalitis (VEE) disease in immunodeficient and immunologically normal mice was compared to define the role of the immune system in this disease process. Immunocompetent mice infected with VEE exhibited a biphasic illness characterized by an early self-limiting lymphoid phase and a fatal CNS phase. The lymphoid phase of the illness was characterized by extensive viral replication within spleen, thymus, Peyer's patches, and lymph nodes, was accompanied by a high-titered serum viremia, and resolved with the production of VEE-specific IgM class antibody at 72 h postinfection (p.i.). Immunocompetent animals survived an average of 6.8 ± 1.2 days before succumbing to fulminant encephalitis. In contrast, SCID mice infected with VEE showed a persistent replication of virus throughout all organs tested beginning at 24 h p.i. VEE-infected SCID mice exhibited a severe spongiform encephalopathy with 100% mortality and an average survival time of 8.9 ± 0.9 days. These studies indicated that the characteristic organ tropism of VEE in the mouse is due in large part to an early anti-viral state, the establishment of which is dependent upon the presence of an intact immune system. Finally, the CNS pathology in a VEE-infected mouse had a significant immunologic component. However, in contrast to other neurovirulent alphaviruses, VEE was directly cytopathic for the cells of the CNS, even in the absence of an immune response

Dutch Outcome in Implantable Cardioverter-Defibrillator Therapy:Implantable Cardioverter-Defibrillator-Related Complications in a Contemporary Primary Prevention Cohort

Background One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications. Conclusions One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits

Validation of circulating steroid hormone measurements across different matrices by liquid chromatography–tandem mass spectrometry

Background: Steroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias

When people co-occur with good or bad events: graded effects of relational qualifiers on evaluative conditioning

Studies on evaluative conditioning show that a change in liking can occur whenever stimuli are paired. Such instances of attitude change are known to depend on the type of relation established between stimuli (e.g., “Bob is a friend of Mike” vs. “Bob is an enemy of Mike”). Research has so far only compared assimilative and contrastive relational qualifiers (e.g., friend vs. enemy). For the first time, we compared the effect of non-oppositional qualifiers on attitude change in a EC procedure (e.g., “Bob causes Positive Outcomes” vs. “Bob predicts Positive Outcomes”). Differential effects of non-oppositional relational qualifiers were observed on explicit and implicit evaluations. We discuss the implications of our findings for attitude research, theories of attitude change, and for optimizing evaluative conditioning for changing attitudes in applied settings

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT)

Background Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. Methods/design The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up i

Accretion of chemically fractionated material on a wide binary with a blue straggler

The components of the wide binary HIP64030=HD 113984 show a large (about 0.25 dex) iron content difference (Desidera et al.~2006 A&A 454, 581). The positions of the components on the color magnitude diagram suggest that the primary is a blue straggler. We studied the abundance difference of several elements besides iron, and we searched for stellar and substellar companions around the components to unveil the origin of the observed iron difference. A line-by-line differential abundance analysis for several elements was performed, while suitable spectral synthesis was performed for C, N, and Li. High precision radial velocities obtained with the iodine cell were combined with available literature data. The analysis of additional elements shows that the abundance difference for the elements studied increases with increasing condensation temperature, suggesting that accretion of chemically fractionated material might have occurred in the system. Alteration of C and N likely due to CNO processing is also observed. We also show that the primary is a spectroscopic binary with a period of 445 days and moderate eccentricity. The minimum mass of the companion is 0.17 Msun. Two scenarios were explored to explain the observed abundance pattern. In the first, all abundance anomalies arise on the blue straggler. If this is the case, the dust-gas separation may have been occurred in a circumbinary disk around the blue straggler and its expected white dwarf companion, as observed in several RV Tauri and post AGB binaries. In the second scenario, accretion of dust-rich material occurred on the secondary. This would also explain the anomalous carbon isotopic ratio of the secondary. Such a scenario requires that a substantial amount of mass lost by the central binary has been accreted by the wide component