Pregnancy-associated placental protein-A (PAPP-A) is a metalloprotease which circulates as an hetero-tetramer in maternal blood. Its maternal serum concentration in fetal trisomy 21 is decreased ...during the first trimester, so that PAPP-A is a useful screening biomarker. However, the regulation of PAPP-A placental secretion is unclear. We therefore investigated the secretion of PAPP-A in pregnancies complicated by fetal aneuploidies, both in vivo and in vitro.
Maternal serum collected between 10 WG and 33 WG during 7014 normal pregnancies and 96 pregnancies complicated by fetal trisomy 21, 18, and 13 were assayed for PAPP-A using the Immulite 2000xpi system®. The pregnancies were monitored using ultrasound scanning, fetal karyotyping and placental analysis. Villous cytotrophoblasts were isolated from normal and trisomic placenta and cultured to investigate PAPP-A secretion in vitro (n=6).
An increased nuchal translucency during the first trimester is a common feature of many chromosomal defect but each aneuploidy has its own syndromic pattern of abnormalities detectable at the prenatal ultrasound scanning and confirmed at the fetal examination thereafter. PAPP-A levels rise throughout normal pregnancy whereas in trisomy 21, PAPP-A levels were significantly decreased, but only during the first trimester. PAPP-A levels were decreased in trisomy 13 and sharply in trisomy 18, whatever the gestational age. In vitro, PAPP-A secretion was decreased in aneuploidy, and associated with decreased hCG secretion in Trisomy 21 and 18. These biochemical profiles did not appear to be linked to any specific histological lesions affecting the placenta.
These profiles may reflect different quantitative and qualitative placental dysfunctions in the context of these aneuploidies.
Background
The videoconference‐based neuropsychological assessment, also called teleneuropsychology, is a promising tool for the diagnosis and follow‐up of individuals living in underserved areas, ...care facilities or other institutions, and even emigrants. This kind of consultation has proved particularly useful during the COVID‐19 pandemic, suggesting how it could be used more systematically. This study is the first to explore the reliability of neuropsychological teleassessment in France.
Method
In the e‐COG study, we included 150 older memory‐complainers, with an MMSE>20, seeking medical advice at a memory clinic (Pitié‐Salpêtrière Hospital) or at the Aloïs Memory Network, both based in Paris, France. At baseline, all participants underwent a comprehensive face‐to‐face neuropsychological assessment. After 4 months, the participants were randomized, so that half of them performed another face‐to‐face assessment, and the other half a teleassessment. For the teleassessment, the examiner used a MacBook Pro system with internet connection, microphone and speaker. The patient was with an assistant with no training in neuropsychology, who intervened during certain tests requiring material handling or physical contact. Two cameras were installed, one to film the entire room, and the other to film what the participant wrote or drew. We compared (i) face‐to‐face versus teleassessment scores using t‐tests and Chi2 tests (or Fisher Exact test when relevant); (ii) scores at assessment 1 versus 2, according to the administration method, using Paired t‐tests and MacNemar tests (or Bowker test when relevant).
Result
Demographic characteristics of the sample are shown in Table 1. The two assessments 4 months apart yielded overall stable scores, regardless of the method of administration (Face‐to‐Face or Video). Very few tests showed significant differences between the two assessments, but the effect size was very weak (all Cohen's d ≤ 0.35). The STAI‐Y‐A score, measuring the level of anxiety felt at the moment, was slightly but non‐significantly higher in the Face‐to‐Face (versus Video) condition (p=0.07), and therefore it seems that the remote assessment does not induce greater anxiety in the patient.
Conclusion
Neuropsychological teleassessment is a valid and promising tool that could be incorporated into the diagnostic and follow‐up processes of patients with suspected or full‐blown cognitive impairment.
Abstract
Background
The videoconference‐based neuropsychological assessment, also called teleneuropsychology, is a promising tool for the diagnosis and follow‐up of individuals living in underserved ...areas, care facilities or other institutions, and even emigrants. This kind of consultation has proved particularly useful during the COVID‐19 pandemic, suggesting how it could be used more systematically. This study is the first to explore the reliability of neuropsychological teleassessment in France.
Method
In the e‐COG study, we included 150 older memory‐complainers, with an MMSE>20, seeking medical advice at a memory clinic (Pitié‐Salpêtrière Hospital) or at the Aloïs Memory Network, both based in Paris, France. At baseline, all participants underwent a comprehensive face‐to‐face neuropsychological assessment. After 4 months, the participants were randomized, so that half of them performed another face‐to‐face assessment, and the other half a teleassessment. For the teleassessment, the examiner used a MacBook Pro system with internet connection, microphone and speaker. The patient was with an assistant with no training in neuropsychology, who intervened during certain tests requiring material handling or physical contact. Two cameras were installed, one to film the entire room, and the other to film what the participant wrote or drew. We compared (i) face‐to‐face versus teleassessment scores using t‐tests and Chi
2
tests (or Fisher Exact test when relevant); (ii) scores at assessment 1 versus 2, according to the administration method, using Paired t‐tests and MacNemar tests (or Bowker test when relevant).
Result
Demographic characteristics of the sample are shown in Table 1. The two assessments 4 months apart yielded overall stable scores, regardless of the method of administration (Face‐to‐Face or Video). Very few tests showed significant differences between the two assessments, but the effect size was very weak (all Cohen's d ≤ 0.35). The STAI‐Y‐A score, measuring the level of anxiety felt at the moment, was slightly but non‐significantly higher in the Face‐to‐Face (versus Video) condition (p=0.07), and therefore it seems that the remote assessment does not induce greater anxiety in the patient.
Conclusion
Neuropsychological teleassessment is a valid and promising tool that could be incorporated into the diagnostic and follow‐up processes of patients with suspected or full‐blown cognitive impairment.
The 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines for the evaluation of left ventricular diastolic function reported a new ...algorithm to assess diastolic function and to estimate left ventricular filling pressure (LVFP). At least five to six different parameters were necessary to conclude, each of them with their own inter-observer variability. This article examines the reproducibility of each parameter of the algorithm and its influence on the final decision of the clinician. Echocardiographic exams of 12 non-selected patients without any known cardiac disease or follow-up but addressed to the hospital for symptoms were analyzed by two readers (one junior and one senior) in five French cardiologic tertiary centers. Inter-observer reproducibility at each step of the algorithm and final decision were analyzed. There was mild agreement on the final decision. The main reasons of discrepancy were disagreement on the significance of mitral annular calcifications and measured values that are just around the cut-off (despite good reproducibility, a slight variation could lead to misclassification of a dichotomous choice between a normal measure and a pathologic measure). Without considering performance, this multicentric French study puts forward limits to the actual algorithm recommended for LVFP pattern assessment. Agreement is excellent in caricatural (easy) cases (left ventricular pressure clearly normal or clearly elevated) but a great discordance exists in the gray zone. Improvement in the algorithm and in the method for LVFP determination is proposed.
Human amniotic membrane (hAM) is considered as an attractive biological scaffold for tissue engineering. For this application, hAM has been mainly processed using cryopreservation, lyophilization ...and/or decellularization. However, no study has formally compared the influence of these treatments on hAM properties. The aim of this study was to develop a new decellularization-preservation process of hAM, and to compare it with other conventional treatments (fresh, cryopreserved and lyophilized).
The hAM was decellularized (D-hAM) using an enzymatic method followed by a detergent decellularization method, and was then lyophilized and gamma-sterilized. Decellularization was assessed using DNA staining and quantification. D-hAM was compared to fresh (F-hAM), cryopreserved (C-hAM) and lyophilized/gamma-sterilized (L-hAM) hAM. Their cytotoxicity on human bone marrow mesenchymal stem cells (hBMSCs) and their biocompatibility in a rat subcutaneous model were also evaluated.
The protocol was effective as judged by the absence of nuclei staining and the residual DNA lower than 50 ng/mg. Histological staining showed a disruption of the D-hAM architecture, and its thickness was 84% lower than fresh hAM (p < 0.001). Despite this, the labeling of type IV and type V collagen, elastin and laminin were preserved on D-hAM. Maximal force before rupture of D-hAM was 92% higher than C-hAM and L-hAM (p < 0.01), and D-hAM was 37% more stretchable than F-hAM (p < 0.05). None of the four hAM were cytotoxic, and D-hAM was the most suitable scaffold for hBMSCs proliferation. Finally, D-hAM was well integrated in vivo.
In conclusion, this new hAM decellularization process appears promising for tissue engineering applications.
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•The human amniotic membrane (hAM) is widely used in the field of tissue engineering.•The various methods used for hAM storage/preservation have never been compared.•Comparison of four popular preservation methods of hAM for tissue engineering applications•Development of a novel and simple decellularization-preservation process of hAM
Retiring From the Family Business Gagnè, Marylène; Wrosch, Carsten; Brun de Pontet, Stephanie
Family business review,
12/2011, Volume:
24, Issue:
4
Journal Article
Peer reviewed
A longitudinal study of family business leaders nearing retirement age examined the effects of goal adjustment capacities (disengagement and reengagement) on retirement planning. Goal disengagement ...predicted taking concrete steps to prepare retirement, whereas goal reengagement was related to having positive retirement expectations. Family business leaders with high goal reengagement capacities who trusted their successor’s abilities set an earlier retirement date than others. Leaders with poor goal disengagement capacities who did not trust their successor were unable to improve their retirement expectations over time. This study shows the importance of psychological variables in the retirement planning process of family business leaders.
Objectives To validate and evaluate an integrated protocol for non‐invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting, using the semiconductor sequencing ...technology, Ion Proton. Methods This prospective cohort study included 2505 pregnant women from seven academic genetic laboratories (695 high risk pregnancies in a validation study and 1810 pregnancies with a risk higher than 1/250 without ultrasound anomalies, in a real NIPS clinical setting). Cell free DNA from plasma samples was sequenced using Ion Proton sequencer, and sequencing data were analyzed using the open‐access software WISECONDOR. Performance metrics for detection of trisomies 21, 18 and 13, were calculated based on either fetal karyotype result or clinical data collected at birth. We also evaluated the failure rate and compared three methods of fetal fraction quantification (RASSF1A assay, DEFRAG and SANEFALCON software). Results Sensitivities and specificities were: 98.3% (95%CI: 93.5 ‐ 99.7) and 99.9% (95%CI: 99.4 ‐ 100) for T21, 96.7% (95%CI: 80.9 ‐ 99.8) and 100% (95%CI: 99.6 ‐ 100) for T18, 94.1% (95%CI: 69.2 ‐ 99.7) and 100% (95%CI: 99.6 ‐ 100) for T13. Our failure rate was 1.2% at first and as low as 0.6% after re‐testing some of the failed samples. Fetal fraction estimation by RASSF1A assay was consistent with DEFRAG results, both of which are adequate for routine diagnosis. Conclusions We describe one of the largest studies evaluating the Ion Proton based NIPS and the first clinical study reporting pregnancy outcome in a large set of patients. We demonstrate that this platform is highly efficient in detecting the three most common trisomies. Our protocol is robust and can be easily implemented in any medical genetics laboratory.
We aimed to compare different methods for semi-quantitative analysis of cardiac retention of bone tracers in patients with cardiac transthyretin amyloidosis (ATTR).
Data from 67 patients with ATTR ...who underwent both conventional whole-body scan and a CZT myocardial SPECT (DSPECT, Spectrum Dynamics) 3 h after injection of
Tc-labeled bone tracer were analyzed. Visual scoring of cardiac retention was performed on whole-body scan according to Perugini 4-point grading system from 0 (no uptake) to 3 (strong cardiac uptake with mild/absent bone uptake). A planar heart-to-background (H:B) ratio was calculated using whole-body scan (wb-H:B). CZT SPECT was quantified using three methods: planar H:B ratio calculated from anterior reprojection (ant-H:B), left anterior oblique reprojection (LAO-H:B), and 3D-H:B ratio calculated from transaxial slices as mean counts in a VOI encompassing the heart divided by background VOI in the contralateral lung. Interventricular septal thickness was obtained using echocardiography.
H:Bs obtained from planar and reprojected data were not statistically different (wb-H:B, 2.05 ± 0.64, ant-H:B, 1.97 ± 0.61, LAO-H:B, 2.06 ± 0.64, all p = ns). However, 3D-H:B was increased compared to planar H:Bs (3D-H:B, 4.06 ± 1.77, all p < 0.0001 vs. wb-H:B, ant-H:B, and LAO-H:B). Bland-Altman plots demonstrated that the difference between 3D and planar H:Bs increased with the mean value of myocardial uptake. 3D-H:B was best correlated to septal thickness (r = 0.45, p < 0.001). Finally, abnormal right ventricular uptake was associated with higher values of cardiac retention.
3D semi-quantitative analysis of CZT SPECT optimized the assessment of
Tc-labeled bone tracer myocardial uptake in patients with cardiac amyloidosis.
The purpose of the study was to describe the pattern of
Tc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin ...cardiac amyloidosis (TTR-CA).
Fifty patients with TTR-CA underwent
Tc- hydroxymethylene-diphosphonate (
Tc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images.
The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial
Tc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184).
These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.
Quantitative assessment of valve regurgitation using volumetric method by comparing right and left ventricular stroke volumes is still under investigations.
To investigate the accuracy of equilibrium ...radionuclide ventriculography (ERV) for the quantification of tricuspid regurgitation (TR) severity.
Thirty-three patients (25 men; mean age 63±10 years) who underwent both ERV and transthoracic echocardiography (TTE) studies within 2 weeks for right ventricular systolic function assessment were eligible for inclusion. Patients with significant mitral regurgitation by TTE were excluded of the study. TR was calculated using the proximal isovelocity surface area (PISA) method from TTE and the volumetric method (right ventricular stroke volume minus left ventricular stroke stroke volume) from ERV.
TR tended to be higher using the ERV volumetric method as compared to PISA method (48±36 vs. 43±31ml, respectively; P=0.06). There was a significant correlation between TR as assess by ERV and by TTE (r=0.8, P<0.001; Fig. 1). Intraclass correlation coefficient between TTE and ERV for TR quantification was 0.9 (P<0.001).
TR assessment using the ERV correlates well with PISA from TTE in patients referred for right ventricular systolic function assessment.
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