Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra)

The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography–mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERa and ERß). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERa. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17ß-estradiol (E2). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20–60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERa or ERß subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E2, not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERa-selective antagonism, similar to the ERa-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E2 by approximately 80% at 6¿×¿10-6 M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERa

Automated coronary artery calcification scoring in non-gated chest CT: Agreement and reliability

Objective: To determine the agreement and reliability of fully automated coronary artery calcium (CAC) scoring in a lung cancer screening population. Materials and Methods: 1793 low-dose chest CT scans were analyzed (non-contrast-enhanced, non-gated). To establish the reference standard for CAC, first automated calcium scoring was performed using a preliminary version of a method employing coronary calcium atlas and machine learning approach. Thereafter, each scan was inspected by one of four trained raters. When needed, the raters corrected initially automaticity-identified results. In addition, an independent observer subsequently inspected manually corrected results and discarded scans with gross segmentation errors. Subsequently, fully automatic coronary calcium scoring was performed. Agatston score, CAC volume and number of calcifications were computed. Agreement was determined by calculating proportion of agreement and examining Bland-Altman plots. Reliability was determined by calculating linearly weighted kappa (κ) for Agatston strata and intraclass correlation coefficient (ICC) for continuous values. Results: 44 (2.5%) scans were excluded due to metal artifacts or gross segmentation errors. In the remaining 1749 scans, median Agatston score was 39.6 (P25-P75:0-345.9), median volume score was 60.4 mm3 (P25-P75:0-361.4) and median number of calcifications was 2 (P25-P75:0-4) for the automated scores. The k demonstrated very good reliability (0.85) for Agatston risk categories between the automated and reference scores. The Bland-Altman plots showed underestimation of calcium score values by automated quantification. Median difference was 2.5 (p25-p75:0.0-53.2) for Agatston score, 7.6 (p25-p75:0.0-94.4) for CAC volume and 1 (p25-p75:0-5) for number of calcifications. The ICC was very good for Agatston score (0.90), very good for calcium volume (0.88) and good for number of calcifications (0.64). Discussion: Fully automated coron

Expression of the insulin-like growth factor (IGF) system and steroidgenic enzymes in canine testis tumors

Testis tumors occur frequently in dogs. The main types of tumors are Sertoli cell tumors, seminomas, and Leydig cell tumors. Mixed tumors and bilateral occurrence of tumors may be encountered frequently. To elucidate the possible relationship between the insulin-like growth factor (IGF) system and the development of different types of testis tumors in dogs, the expression of insulin-like growth factor-I and II (IGF-I and IGF-II), their type I receptor (IGF-IR), and their binding proteins (IGFBPs) was examined. In addition the expression of the steroidogenic enzymes p450-aromatase and 5α-reductase type I and type II, and the androgen receptor (AR) was investigated by a semiquantitative reverse-transcriptase PCR (RT-PCR). Both normal testes and testes with tumors were studied. In normal testes a clear expression of IGF-I, IGF-II, IGF-IR, IGFBP2, IGFBP4 and IGFBP5 was found. Expression of IGFBP1 and IGFBP3 was weak. There was also clear expression of the steroidogenic enzymes 5α-reductase, aromatase, and the AR. Quantification of RT-PCR products revealed significantly less expression of IGFBP1, IGF-I, and 5α-reductase type I in Sertoli cell tumors and seminomas. Leydig cell tumors and mixed tumors had a significantly higher expression of IGFBP4 and IGF-IR than normal testes. The expression of aromatase was lower in seminomas and in mixed tumors. The expression of AR, IGF-II and IGFBP2, IGFBP3, IGFBP5, and 5α-reductase type II did not differ among the different types of tumors. It was concluded that Sertoli cell tumors and seminomas have a comparable expression of the IGF system while Leydig cell tumors have a different pattern, suggesting difference in pathobiology among these types of tumors

Using self-regulation assessment to explore associations between self-regulation, participation and health-related quality of life in a rehabilitation population

Objective: Self-regulation, participation and health-related quality of life are important rehabilitation outcomes. The aim of this study was to explore associations between these outcomes in a multi-diagnostic and heterogenic group of former rehabilitation patients.Methods: This cross-sectional survey used the Self-Regulation Assessment (SeRA), Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) and the Patient-Reported-Outcome-Measurement-System (PROMIS) ability and PROMIS satisfaction with participation in social roles, and the EuroQol-5L-5D and PROMIS-10 Global Health. Regression analyses, controlling for demographic and condition-related factors, were performed.Results: Respondents (n=563) had a mean age of 56.5 (standard deviation (SD) 12.7) years. The largest diagnostic groups were chronic pain disorder and brain injury. In addition to demographic and condition-related factors, self-regulation subscales explained 0–15% of the variance in participation outcome scores, and 0–22% of the variance in HRQoL outcome scores. Self-regulation subscales explained up to 22% of the variance in satisfaction subscales of participation (USER-Participation and PROMIS) and the mental health subscale of the PROMIS-10. Self-regulation subscales explained up to 11% of the restriction and frequency subscales of participation (USER-Participation) and the physical health subscale of the PROMIS-10.Conclusion: Self-regulation is more strongly associated with outcomes such as satisfaction with participation and mental health compared with outcomes such as restrictions in participation and physical health.</p

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: A multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Trial registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675. EudraCT-registration number: 2015-003220-31

Clinically SUspected ScaPhoid fracturE: treatment with supportive bandage or CasT? 'Study protocol of a multicenter randomized controlled trial' (SUSPECT study)

Introduction Some scaphoid fractures become visible on radiographs weeks after a trauma which makes normal radiographs directly after trauma unreliable. Untreated scaphoid fractures can lead to scaphoid non-union progressing to osteoarthritis. Therefore, the general treatment for patients with a clinically suspected scaphoid fracture and normal initial radiographs is immobilisation with below-elbow cast for 2 weeks. However, most of these patients are treated unnecessarily because eventually less than 10% of them are diagnosed with an occult scaphoid fracture. To reduce overtreatment and costs as a result of unnecessary cast treatment in patients with a clinically suspected scaphoid fracture and normal initial radiographs, we designed a study to compare below-elbow cast treatment with supportive bandage treatment. We hypothesise that the functional outcome after 3 months is not inferior in patients treated with supportive bandage compared to patients treated with below-elbow cast, but with lower costs in the supportive bandage group. Methods and analysis The SUSPECT study is an open-labelled multicentre randomised controlled trial with non-inferiority design. A total of 180 adult patients with a clinically suspected scaphoid fracture and normal initial radiographs are randomised between two groups: 3 days of supportive bandage or 2 weeks of below-elbow cast. We aim to evaluate the functional outcome and cost-effectiveness of both treatments. The primary outcome is the functional outcome after 3 months, assessed with the Quick Disability of the Arm, Shoulder and Hand score. Secondary outcomes include functional outcome, recovery of function, pain, patient satisfaction, quality of life and cost-effectiveness measured by medical consumption, absence from work or decreased productivity. Ethics and dissemination The Medical Ethics Committee of the Erasmus MC Medical Centre, Rotterdam, approved the study protocol (MEC-2017-504). We plan to present the results after completion of the study at (inter)national conferences and publish in general peer-reviewed journals