A pilot study comparing the DuoFertility(®) monitor with ultrasound in infertile women.

BACKGROUND: The purpose of this study was to assess the accuracy of ovulation detection by the DuoFertility(®) monitor compared with transvaginal ultrasound in infertile women with regular menstrual cycles. METHODS: Eight infertile patients, aged 27-40 years, with a body mass index of 19-29, regular menses, normal ovaries on pelvic ultrasound scan, and normal early follicular luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were recruited from infertility clinics in primary and secondary care for this pilot, prospective, observational study. The patients were asked to use the DuoFertility monitor for the whole cycle, with investigators and patients blind to DuoFertility data. Daily urine LH monitoring commenced on cycle day 8, with daily transvaginal ultrasound following the first positive LH until ovulation was observed. Ovulation was further confirmed by serum progesterone. The main outcome measure was detection of ovulation by the DuoFertility monitor, and correlation between day of ovulation assessed by DuoFertility and ultrasound. RESULTS: DuoFertility identified ovulation as having occurred within one day of that determined via ultrasound in all cycles. The sensitivity of ovulation detection was 100% (95% confidence interval 82-100). The specificity could not be concluded from the data. CONCLUSION: In infertile women with regular cycles, the DuoFertility monitor appears to accurately identify ovulatory cycles and the day of ovulation

Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1)

Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described

Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary?

© 2016 Hamshere et al. Background: AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR). Methods: CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers. Results: 85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 ± 3.21 %, 95 % limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001. Conclusions: AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians

Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom

Aims: Understanding the spectrum of disease, symptom burden and natural history are essential for the management of children with hypertrophic cardiomyopathy (HCM). The effect of changing screening practices over time has not previously been studied. This study describes the clinical characteristics and outcomes of childhood HCM over four decades in a well-characterized United Kingdom cohort. Methods and results: Six hundred and eighty-seven patients with HCM presented at a median age of 5.2 years (range 0-16). Aetiology was: non-syndromic (n = 433, 63%), RASopathy (n = 126, 18.3%), Friedreich's ataxia (n = 59, 8.6%) or inborn errors of metabolism (IEM) (n = 64, 9%). In infants (n = 159, 23%) underlying aetiology was more commonly a RASopathy (42% vs. 11.2%, P < 0.0001) or IEM (18.9% vs. 6.4% P < 0.0001). In those with familial disease, median age of presentation was higher (11 years vs. 6 years, P < 0.0001), 141 (58%) presented <12 years. Freedom from death or transplantation was 90.6% (87.9-92.7%) at 5 years (1.5 per 100 patient years) with no era effect. Mortality was most frequently sudden cardiac death (SCD) (n = 20, 2.9%). Children diagnosed during infancy or with an IEM had a worse prognosis (5-year survival 80.5% or 66.4%). Arrhythmic events occurred at a rate of 1.2 per 100 patient years and were more likely in non-syndromic patients (n = 51, 88%). Conclusion: This national study describes a heterogeneous disease whose outcomes depend on the age of presentation and aetiology. Overall mortality and SCD rates have not changed over time, but they remain higher than in adults with HCM, with events occurring in syndromic and non-syndromic patients

Validation of the WHO Disability Assessment Schedule (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and history of severe maternal morbidity

© 2018 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. Objective: To validate the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item tool against the 36-item version for measuring functioning and disability associated with pregnancy and the occurrence of maternal morbidity. Methods: This is a secondary analysis of the Brazilian retrospective cohort study on long-term repercussions of severe maternal morbidity (SMM) among women who delivered at a tertiary facility (COMMAG study). We compared WHODAS-12 and WHODAS-36 scores of women with and without SMM using measures of central tendency and variability, tests for instruments’ agreement (Bland-Altman plot), confirmatory factor analysis (CFA), and Cronbach alpha coefficient for internal consistency. Results: The COMMAG study enrolled 638 women up to 5 years postpartum. Although the median WHODAS-36 and -12 scores for all women were statistically different (13.04 and 11.76, respectively; P<0.001), there was a strong linear correlation between them. Furthermore, the mean difference and the differences in variance analyses demonstrated agreement of total scores between the two versions. CFA demonstrated how the WHODAS-12 questions are divided into six previously defined factors and Cronbach alpha showed good internal consistency. Conclusion: WHODAS-12 demonstrated agreement with WHODAS-36 for total score and was a good instrument for screening functioning and disability among postpartum women, with and without SMM

The impact of hypertension, hemorrhage, and other maternal morbidities on functioning in the postpartum period as assessed by the WHODAS 2.0 36-item tool

© 2018 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. Objective: To assess the scores of postpartum women using the WHO Disability Assessment Schedule 2.0 36-item tool (WHODAS-36), considering different morbidities. Methods: Secondary analysis of a retrospective cohort of women who delivered at a referral maternity in Brazil and were classified with and without severe maternal morbidity (SMM). WHODAS-36 was used to assess functioning in postpartum women. Percentile distribution of total WHODAS score was compared across three groups: Percentile (P)90. Cases of SMM were categorized and WHODAS-36 score was assessed according to hypertension, hemorrhage, or other conditions. Results: A total of 638 women were enrolled: 64 had mean scores below P90 (41.3). Of women scoring above P>90, those with morbidity had a higher mean score than those without (44.6% vs 36.8%, P=0.879). Women with higher WHODAS-36 scores presented more complications during pregnancy, especially hypertension (47.0% vs 37.5%, P=0.09). Mean scores among women with any complication were higher than those with no morbidity (19.0 vs 14.2, P=0.01). WHODAS-36 scores were higher among women with hypertensive complications (19.9 vs 16.0, P=0.004), but lower among those with hemorrhagic complications (13.8 vs 17.7, P=0.09). Conclusions: Complications during pregnancy, childbirth, and the puerperium increase long-term WHODAS-36 scores, demonstrating a persistent impact on functioning among women, up to 5 years postpartum

A validation study of the European Society of Cardiology guidelines for risk stratification of sudden cardiac death in childhood hypertrophic cardiomyopathy

AIMS: Sudden cardiac death (SCD) is the most common cause of death in children with hypertrophic cardiomyopathy (HCM). The European Society of Cardiology (ESC) recommends consideration of an implantable cardioverter-defibrillator (ICD) if two or more clinical risk factors (RFs) are present, but this approach to risk stratification has not been formally validated. METHODS AND RESULTS: Four hundred and eleven paediatric HCM patients were assessed for four clinical RFs in accordance with current ESC recommendations: severe left ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia, and family history of SCD. The primary endpoint was a composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate ICD therapy, or sustained ventricular tachycardia), defined as a major arrhythmic cardiac event (MACE). Over a follow-up period of 2890 patient years (median 5.5 years), MACE occurred in 21 patients (7.5%) with 0 RFs, 19 (16.8%) with 1 RFs, and 3 (18.8%) with 2 or more RFs. Corresponding incidence rates were 1.13 [95% confidence interval (CI) 0.7-1.73], 2.07 (95% CI 1.25-3.23), and 2.52 (95% CI 0.53-7.35) per 100 patient years at risk. Patients with two or more RFs did not have a higher incidence of MACE (log-rank test P = 0.34), with a positive and negative predictive value of 19% and 90%, respectively. The C-statistic was 0.62 (95% CI 0.52-0.72) at 5 years. CONCLUSIONS: The incidence of MACE is higher for patients with increasing numbers of clinical RFs. However, the current ESC guidelines have a low ability to discriminate between high- and low-risk individuals

Space Telescope and Optical Reverberation Mapping Project. VII. Understanding the Ultraviolet Anomaly in NGC 5548 with X-Ray Spectroscopy

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly

Platelet-Rich Plasma Promotes the Proliferation of Human Muscle Derived Progenitor Cells and Maintains Their Stemness

Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs. © 2013 Li et al