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1.
Ultrasound Obstet Gynecol ; 62(4): 540-551, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37204929

ABSTRACT

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

2.
IEEE Comput Graph Appl ; 41(5): 99-103, 2021.
Article in English | MEDLINE | ID: mdl-34506271

ABSTRACT

Rayground is a novel online framework for fast prototyping and interactive demonstration of ray tracing algorithms. It aims to set the ground for the online development of ray-traced visualization algorithms in an accessible manner for everyone, stripping off the mechanics that get in the way of creativity and the understanding of the core concepts. Due to the COVID-19 pandemic, remote teaching and online coursework have taken center stage. In this work, we demonstrate how Rayground can incorporate advanced instructive rendering media during online lectures as well as offer attractive student assignments in an engaging, hands-on manner. We cover things to consider when building or porting methods to this new development platform, best practices in remote teaching and learning activities, and time-tested assessment and grading strategies suitable for fully online university courses.

3.
Folia Morphol (Warsz) ; 80(3): 718-721, 2021.
Article in English | MEDLINE | ID: mdl-32827311

ABSTRACT

Vascular anatomical variations of the abdomen are very common. Awareness of these variations is of paramount importance in clinical practice mainly in achieving best results in minimal invasive or surgical vascular procedures. From surgical point of view, the preoperative knowledge of vascular anatomy and the relations to the surrounding structures and tissues aims to minimise inadvertent complications. Agenesis of the coeliac trunk is one of the rare anatomical variations of the abdominal aorta. Limited number of cases have been reported in the medical literature, most of which are based on angiographic and cadaveric studies of adult humans. In this paper, we report a case of absence of the coeliac trunk that has been detected as an incidental radiological finding in a female patient who was admitted with abdominal pain.


Subject(s)
Celiac Artery , Hepatic Artery , Adult , Angiography , Aorta, Abdominal/diagnostic imaging , Celiac Artery/diagnostic imaging , Female , Humans , Splenic Artery
4.
Environ Pollut ; 266(Pt 2): 115136, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32650203

ABSTRACT

In compliance to European Union directives to reuse urban wastes as secondary fuels, the aim of present work was to investigate and control the environmental impact from disposal of ashes generated by combustion of a bio-solid, an olive by-product and their blend. Two waste materials were admixed with the ash and their performance as potential stabilizers was assessed. Metals and ions leached through a soil were measured. The results showed that dissolution of some alkaline substances raised the pH of water effluents, decreasing the extractability of heavy metals from the ashes. In some cases Cr and As leached reached hazardous levels. Upon addition of waste materials to ash, the concentration of Cr in liquid extracts was reduced by 35-97%, while that of Cu and As by 100%. All heavy metal values measured in the leachates were decreased to values below legislation limits. The mineralogy, the chemistry and the pH of solids involved were key factors for the retention of elements.


Subject(s)
Metals, Heavy/analysis , Olea , Refuse Disposal , Coal Ash , Incineration , Soil
5.
Ultrasound Obstet Gynecol ; 53(1): 55-61, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29573501

ABSTRACT

OBJECTIVE: To develop a first-trimester or combined first- and second-trimester screening algorithm for the prediction of small-for-gestational age (SGA) and late fetal growth restriction (FGR). METHODS: This was a retrospective study of women with singleton pregnancy, who underwent routine first-, second- and third-trimester ultrasound assessment. Late FGR was defined, at ≥ 32 weeks' gestation in the absence of congenital anomalies, as either (i) estimated fetal weight (EFW) or birth weight (BW) < 3rd centile, or (ii) EFW < 10th centile and either uterine artery mean pulsatility index (UtA-PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile. Neonates with BW < 10th centile, regardless of prenatal parameters, were defined as SGA. The predictive effectiveness of maternal and first- and second-trimester factors was tested using logistic regression and receiver-operating characteristics curve analyses. RESULTS: A total of 3520 fetuses were included (late FGR, n = 109 (3.1%); SGA, n = 292 (8.3%)). Of the late FGR cases, 56 (1.6%) fulfilled the antenatal criteria (EFW < 3rd centile or EFW < 10th centile plus abnormal UtA-PI or CPR) and were defined as prenatally detected late FGR. A first-trimester screening model (comprising conception method, smoking status, maternal height, pregnancy-associated plasma protein-A (PAPP-A) and UtA-PI) could predict 50.0% of the prenatally diagnosed and 36.7% of the overall late FGR fetuses for a 10% false-positive rate (FPR). A model combining first- and second-trimester screening parameters (conception method, smoking status, PAPP-A, second- trimester EFW, head circumference/abdominal circumference ratio and UtA-PI) could predict 78.6% of the prenatally detected, and 59.6% of the overall late FGR fetuses, for a 10% FPR (area under the curve 0.901 (95% CI, 0.856-0.947) and 0.855 (95% CI, 0.818-0.891), respectively). The prediction of SGA was suboptimal for both first-trimester and combined screening. CONCLUSIONS: A simple model combining maternal and first- and second-trimester predictors can detect 60% of fetuses that will develop late FGR, and 79% of those fetuses that will be classified prenatally as late FGR, for a 10% FPR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Algorithms , Fetal Growth Retardation/diagnosis , Infant, Small for Gestational Age , Ultrasonography, Prenatal , Adult , Female , Humans , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Retrospective Studies
6.
Ultrasound Obstet Gynecol ; 52(2): 186-195, 2018 08.
Article in English | MEDLINE | ID: mdl-29896812

ABSTRACT

OBJECTIVE: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated. RESULTS: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively. CONCLUSION: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.


Subject(s)
Placenta Growth Factor/blood , Pre-Eclampsia/diagnosis , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/metabolism , Risk Assessment/methods , Uterine Artery/physiopathology , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Arterial Pressure/physiology , Bayes Theorem , Biomarkers/blood , Female , Gestational Age , Humans , Pregnancy , Prospective Studies , Pulsatile Flow/physiology
7.
Ultrasound Obstet Gynecol ; 52(1): 52-59, 2018 07.
Article in English | MEDLINE | ID: mdl-29704277

ABSTRACT

OBJECTIVES: To examine the effect of first-trimester screening for pre-eclampsia (PE) on the prediction of delivering a small-for-gestational-age (SGA) neonate and the effect of prophylactic use of aspirin on the prevention of SGA. METHODS: The data for this study were derived from two multicenter studies. In SPREE, we investigated the performance of screening for PE by a combination of maternal characteristics and biomarkers at 11-13 weeks' gestation. In ASPRE, women with a singleton pregnancy identified by combined screening as being at high risk for preterm PE (> 1 in 100) participated in a trial of aspirin (150 mg/day from 11-14 until 36 weeks' gestation) compared to placebo. In this study, we used the data from the ASPRE trial to estimate the effect of aspirin on the incidence of SGA with birth weight < 10th , < 5th and < 3rd percentile for gestational age. We also used the data from SPREE to estimate the proportion of SGA in the pregnancies with a risk for preterm PE of > 1 in 100. RESULTS: In SPREE, screening for preterm PE by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor identified a high-risk group that contained about 46% of SGA neonates < 10th percentile born at < 37 weeks' gestation (preterm) and 56% of those born at < 32 weeks (early); the overall screen-positive rate was 12.2% (2014 of 16 451 pregnancies). In the ASPRE trial, use of aspirin reduced the overall incidence of SGA < 10th percentile by about 40% in babies born at < 37 weeks' gestation and by about 70% in babies born at < 32 weeks; in babies born at ≥ 37 weeks, aspirin did not have a significant effect on incidence of SGA. The aspirin-related decrease in incidence of SGA was mainly due to its incidence decreasing in pregnancies with PE, for which the decrease was about 70% in babies born at < 37 weeks' gestation and about 90% in babies born at < 32 weeks. On the basis of these results, it was estimated that first-trimester screening for preterm PE and use of aspirin in the high-risk group would potentially reduce the incidence of preterm and early SGA by about 20% and 40%, respectively. CONCLUSION: First-trimester screening for PE by the combined test identifies a high proportion of cases of preterm SGA that can be prevented by the prophylactic use of aspirin. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.


Subject(s)
Aspirin/therapeutic use , Fetal Growth Retardation/prevention & control , Placenta Growth Factor/blood , Platelet Aggregation Inhibitors/therapeutic use , Pre-Eclampsia/prevention & control , Pregnancy-Associated Plasma Protein-A/metabolism , Uterine Artery/diagnostic imaging , Adult , Biomarkers/blood , Female , Fetal Growth Retardation/diagnosis , Gestational Age , Humans , Infant, Newborn , Infant, Small for Gestational Age , Mass Screening , Pre-Eclampsia/diagnosis , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First , Prenatal Diagnosis
8.
Ultrasound Obstet Gynecol ; 51(6): 738-742, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29380918

ABSTRACT

OBJECTIVE: To report the incidence of preterm pre-eclampsia (PE) in women who are screen positive according to the criteria of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), and compare the incidence with that in those who are screen positive or screen negative by The Fetal Medicine Foundation (FMF) algorithm. METHODS: This was a secondary analysis of data from the ASPRE study. The study population consisted of women with singleton pregnancy who underwent prospective screening for preterm PE by means of the FMF algorithm, which combines maternal factors and biomarkers at 11-13 weeks' gestation. The incidence of preterm PE in women fulfilling the NICE and ACOG criteria was estimated; in these patients the incidence of preterm PE was then calculated in those who were screen negative relative to those who were screen positive by the FMF algorithm. RESULTS: A total of 34 573 women with singleton pregnancy delivering at ≥ 24 weeks' gestation underwent prospective screening for preterm PE, of which 239 (0.7%) cases developed preterm PE. At least one of the ACOG criteria was fulfilled in 22 287 (64.5%) pregnancies and the incidence of preterm PE was 0.97% (95% CI, 0.85-1.11%); in the subgroup that was screen positive by the FMF algorithm the incidence of preterm PE was 4.80% (95% CI, 4.14-5.55%), and in those that were screen negative it was 0.25% (95% CI, 0.18-0.33%), with a relative incidence in FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In 1392 (4.0%) pregnancies, at least one of the NICE high-risk criteria was fulfilled, and in this group the incidence of preterm PE was 5.17% (95% CI, 4.13-6.46%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93-10.89%) and 0.65% (95% CI, 0.25-1.67%), respectively, and the relative incidence was 0.075 (95% CI, 0.028-0.205). In 2360 (6.8%) pregnancies fulfilling at least two of the NICE moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28-2.35%); in the subgroups of screen positive and screen negative by the FMF algorithm the incidence was 4.91% (95% CI, 3.54-6.79%) and 0.42% (95% CI, 0.20-0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192). CONCLUSION: In women who are screen positive for preterm PE by the ACOG or NICE criteria but screen negative by the FMF algorithm, the risk of preterm PE is reduced to within or below background levels. The results provide further evidence to support the personalized risk-based screening method that combines maternal factors and biomarkers. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Pre-Eclampsia/epidemiology , Prenatal Diagnosis , Adult , Algorithms , Clinical Trials as Topic , Europe/epidemiology , Female , Humans , Incidence , Practice Guidelines as Topic , Pre-Eclampsia/diagnosis , Pregnancy , Pregnancy Trimester, First , Prospective Studies , Risk Factors
10.
Ultrasound Obstet Gynecol ; 50(4): 492-495, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28741785

ABSTRACT

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Aspirin/therapeutic use , Mass Screening/methods , Platelet Aggregation Inhibitors/therapeutic use , Pre-Eclampsia/diagnosis , Pre-Eclampsia/prevention & control , Uterine Artery/diagnostic imaging , Adult , Algorithms , Biomarkers/blood , Double-Blind Method , Female , Humans , Placenta Growth Factor/blood , Pregnancy , Pregnancy Trimester, First , Pregnancy-Associated Plasma Protein-A/metabolism , Prospective Studies , Research Design , Young Adult
11.
Ultrasound Obstet Gynecol ; 49(6): 756-760, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28295782

ABSTRACT

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Biomarkers/blood , Practice Guidelines as Topic , Pre-Eclampsia/diagnosis , Prenatal Diagnosis , Female , Gestational Age , Humans , Pre-Eclampsia/blood , Pregnancy , Pregnancy Trimester, First , Prospective Studies , ROC Curve , Risk Assessment , Societies, Medical , United Kingdom , United States
12.
Eur Ann Allergy Clin Immunol ; 48(6): 251-255, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27852432

ABSTRACT

Febuxostat is a xanthine oxidase inhibitor that during the last years has successfully replaced allopurinol treatment in patients with chronic kidney disease (CKD) and hyperuricemia. Several adverse events have been observed during therapy with febuxostat. DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome induced by febuxostat has been poorly described, mainly in patient with CKD who previously developed allopurinol hypersensitivity syndrome. DRESS syndrome is characterized by manifold cutaneous reactions and systemic disorders with potential devastating consequences. The underlying pathogenetic mechanisms remain unidentified, though immune responses are often complicated. P-i concept can partially explain the phenomenon. The role of renal insufficiency appears to be crucial and further investigation is required. The present article describes the case of a CKD patient that developed febuxostat-related DRESS syndrome.


Subject(s)
Drug Hypersensitivity Syndrome/etiology , Febuxostat/adverse effects , Gout Suppressants/adverse effects , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/drug therapy
13.
J Endocrinol Invest ; 39(4): 439-46, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26507391

ABSTRACT

PURPOSE: Aromatase inhibitors have been used to increase predicted adult height (PAH) in boys but in girls only in McCune-Albright syndrome. We investigated whether anastrozole combined with leuprorelin for up to 2 years is safe and effective in improving PAH in girls with early puberty and compromised growth, compared to leuprorelin alone. METHODS: The "GAIL" study: girls treated with an aromatase inhibitor and an LHRH analogue, ISRCTN11469487, was a 7-year prospective phase IIa study with parallel design, performed at Athens Medical Center (C-A), and Attikon University Hospital, Athens, Greece (C-B). Forty girls, consecutively referred for early puberty (onset 7.5-9 years) with a PAH <-2 or >1.5 SD lower than their target height (TH), were included. Twenty started on leuprorelin sc/im 0.3 mg/kg/month plus anastrozole 1 mg/d p.o. (group-A, C-A) and 20 on leuprorelin (group-B, C-B) for 2 years or until the age of 10 years. Groups did not differ in age, height, BMI, bone age advancement (BAA), and distance of PAH from TH. Follow-up was at 6, 12, 18, and 24 m. RESULTS: Reduction in BAA was significantly higher in group-A compared to group-B already by 6 m. Despite the transiently significant decrease in height velocity in group-A, gain in PAH SD was almost double by 12 and 18 m vs group-B and reached the maximum of +1.21 ± 0.45 (7.51 cm) vs +0.31 ± 0.37 (1.92 cm, p = 0.001) in group-B at 24 m. Group-A had no clinical or biochemical hyperandrogenism, unchanged normal bone density, and lumbar spine X-rays. CONCLUSION: The co-administration of anastrozole with leuprorelin safely improves PAH in girls with compromised growth.


Subject(s)
Aromatase Inhibitors/therapeutic use , Growth Disorders/drug therapy , Leuprolide/therapeutic use , Nitriles/therapeutic use , Triazoles/therapeutic use , Anastrozole , Body Height/drug effects , Bone Density , Case-Control Studies , Child , Female , Follow-Up Studies , Gonadotropin-Releasing Hormone/metabolism , Greece/epidemiology , Growth Disorders/epidemiology , Humans , Prognosis , Prospective Studies , Puberty, Precocious , Sexual Maturation/drug effects
15.
Osteoarthritis Cartilage ; 23(7): 1214-20, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25707934

ABSTRACT

OBJECTIVE: In growth plate chondrocytes, loss of Dicer, a microRNA (miRNA)-processing enzyme, causes defects in proliferation and differentiation, leading to a lethal skeletal dysplasia. However roles of miRNAs in articular chondrocytes have not been defined in vivo. To investigate the role of miRNAs in articular chondrocytes and to explore the possibility of generating a novel mouse osteoarthritis (OA) model caused by intrinsic cellular dysfunction, we ablated Drosha, another essential enzyme for miRNA biogenesis, exclusively in articular chondrocytes of postnatal mice. DESIGN: First, to confirm that the essential role of miRNAs in skeletal development, we ablated the miRNA biogenesis pathway by deleting Drosha or DGCR8 in growth plate chondrocytes. Next, to investigate the role of miRNAs in articular cartilage, we deleted Drosha using Prg4-CreER(T) transgenic mice expressing a tamoxifen-activated Cre recombinase (CreER(T)) exclusively in articular chondrocytes. Tamoxifen was injected at postnatal days, 7, 14, 21, and 28 to ablate Drosha. RESULTS: Deletion of Drosha or DGCR8 in growth plate chondrocytes caused a lethal skeletal defect similar to that of Dicer deletion, confirming the essential role of miRNAs in normal skeletogenesis. Early postnatal Drosha deletion in articular chondrocytes significantly increased cell death and decreased Safranin-O staining. Mild OA-like changes, including surface erosion and cleft formation, were found in male mice at 6 months of age; however such changes in females were not observed even at 9 months of age. CONCLUSIONS: Early postnatal Drosha deficiency induces articular chondrocyte death and can cause a mild OA-like pathology.


Subject(s)
Cartilage, Articular/pathology , Chondrocytes/pathology , Osteoarthritis/pathology , Ribonuclease III/physiology , Animals , Arthritis, Experimental/enzymology , Arthritis, Experimental/genetics , Arthritis, Experimental/pathology , Bone Diseases, Developmental/enzymology , Bone Diseases, Developmental/genetics , Bone Diseases, Developmental/pathology , Cell Death/genetics , Cell Death/physiology , Female , Gene Deletion , Growth Plate/pathology , Male , Mice, Knockout , Mice, Transgenic , MicroRNAs/genetics , Osteoarthritis/enzymology , Osteoarthritis/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/physiology , Ribonuclease III/deficiency , Ribonuclease III/genetics , Tamoxifen
16.
Nanotechnology ; 22(20): 205708, 2011 May 20.
Article in English | MEDLINE | ID: mdl-21444948

ABSTRACT

This work presents a novel characterization methodology for the dielectric charging phenomenon in electrostatically driven MEMS devices using Kelvin probe force microscopy (KPFM). It has been used to study plasma-enhanced chemical vapor deposition (PECVD) silicon nitride thin films in view of application in electrostatic capacitive RF MEMS switches. The proposed technique takes the advantage of the atomic force microscope (AFM) tip to simulate charge injection through asperities, and then the induced surface potential is measured. The impact of bias amplitude, bias polarity, and bias duration employed during charge injection has been explored. The influence of various parameters on the charging/discharging processes has been investigated: dielectric film thickness, SiN(x) material deposition conditions, and under layers. Fourier transform infrared spectroscopy (FT-IR) and x-ray photoelectron spectroscopy (XPS) material characterization techniques have been used to determine the chemical bonds and compositions, respectively, of the SiN(x) films being investigated. The required samples for this technique consist only of thin dielectric films deposited over planar substrates, and no photolithography steps are required. Therefore, the proposed methodology provides a low cost and quite fast solution compared to other available characterization techniques of actual MEMS switches. Finally, the comparison between the KPFM results and the discharge current transients (DCT) measurements shows a quite good agreement.

17.
J Colloid Interface Sci ; 358(1): 1-13, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21444091

ABSTRACT

In this work, for the first time different stiction mechanisms in electrostatic micro-electromechanical systems (MEMS) switches were studied. In these devices stiction can be caused by two main mechanisms: dielectric charging and meniscus formation resulting from the adsorbed water film between the switch bridge and the dielectric layer. The effect of each mechanism and their interaction were investigated by measuring the adhesive and friction forces under different electrical stress conditions and relative humidity levels. An atomic force microscope (AFM) was used to perform force-distance and friction measurements on the nanoscale. A novel technique was proposed to measure the induced surface potential over the dielectric surface and was used to explain the obtained adhesive and friction results. The evolution of adhesive force with time was monitored in order to study the charging/discharging processes in the dielectric film. The assessment methodology is employed for application in RF-MEMS switches and could be extended to other electrostatic MEMS devices. The study provides an in-depth understanding of different stiction mechanisms, and explanation for the literature reported device level measurements for electrostatic capacitive MEMS switches.

18.
Nanotechnology ; 22(3): 035705, 2011 Jan 21.
Article in English | MEDLINE | ID: mdl-21149964

ABSTRACT

In this paper, we investigate the impact of environment gases and relative humidity on dielectric charging phenomenon in electrostatically actuated micro- and nano-electromechanical systems (MEMS and NEMS). The research is based on surface potential measurements using Kelvin probe force microscopy (KPFM). Plasma-enhanced chemical vapor deposition (PECVD) silicon nitride films were investigated in view of applications in electrostatic capacitive RF MEMS switches. Charges were injected through the atomic force microscope (AFM) tip, and the induced surface potential was measured using KPFM. Experiments have been performed in air and in nitrogen environments, both under different relative humidity levels ranging from 0.02% to 40%. The impact of oxygen gas and hydrocarbon contaminants has been studied for the first time by using different gas purifiers in both air and nitrogen lines. Voltage pulses with different bias amplitudes have been applied during the charge injection step under all investigated environmental conditions in order to investigate the effect of bias amplitude. The investigation reveals a deeper understanding of charging and discharging processes and could further lead to improved operating environment conditions in order to minimize the dielectric charging. Finally, the nanoscale KPFM results obtained in this study show a good correlation with the device level measurements for capacitive MEMS switches reported in the literature.

19.
J Biomech ; 43(5): 871-8, 2010 Mar 22.
Article in English | MEDLINE | ID: mdl-20047746

ABSTRACT

The design, construction, and fitting of artificial limbs remain to this day an art, dependent on the accumulated expertise of the practitioner/prosthetist. Socket fitting is cost ineffective, time consuming, and a source of inconvenience for the amputee. Stump-skin slippage within the socket can cause discomfort, internal limb pain, and eventually skin ulcers as a result of excessive pressure and shear within the socket. This study presents a new method of assessment of three-dimensional (3D) socket-stump kinematics/slippage of strenuous activities using Biplane Dynamic Roentgen Stereogrammetric Analysis instrumentation. Ten below knee amputees participated in the study. A more holistic representation of the downward slippage trend of all proximal side skin markers with respect to the socket, and an even more characteristic and of higher magnitude downward-and anterioposterior slippage (maximum slippage: 151 mm for the fast-stop task and 19 mm for the step-down task) between the distal markers after impact, was possible for both tasks for all amputees. Displacement between skin-to-skin marker pairs reached maximum values of approximately 10mm for the step-down trials and up to 24 mm for the fast stop trials. Maximum skin strain was dependent on the position of the skin markers. Distally positioned skin marker pairs demonstrated mainly anterioposterior displacement between each other (maximum relative strain: 13-14%). Maximum relative strain for the proximal markers was 8-10%. This highly accurate, in-vivo, patient-specific, unobtrusive dynamic information, presented using 3D visualization tools that were up to now unavailable to the clinician-prosthetist, can significantly impact the iterative cycle of socket fitting and evaluation.


Subject(s)
Amputation Stumps/diagnostic imaging , Amputation Stumps/physiopathology , Artificial Limbs , Physical Exertion , Tibia/diagnostic imaging , Tibia/physiopathology , Tomography, X-Ray Computed/methods , Computer Simulation , Elastic Modulus , Equipment Failure Analysis , Female , Humans , Imaging, Three-Dimensional/methods , Male , Models, Biological , Motion , Prosthesis Design , Shear Strength , Stress, Mechanical
20.
Toxicol Ind Health ; 25(4-5): 231-9, 2009.
Article in English | MEDLINE | ID: mdl-19651792

ABSTRACT

Inhaled tobacco smoke comes in direct contact with few organs such as mouth, lungs, and stomach. Cigarette smoke (CS) in lungs has been extensively studied. However, limited data exist on its effect on skin, and there are no long-term experimental studies suggesting toxic effects on skin. Even though it is generally accepted that CS is among the main factors of skin aging, the number of experimental studies showing this aging effect is limited. We hereby studied the effect of long-term exposure to CS on the skin of hairless mice in combination with or without ultraviolet (UV) light. In addition, we investigated potential skin protection by a potent antioxidant namely procyanidine-rich French maritime pine bark extract (PBE) pycnogenol. Male and female hairless SKH-2 mice were exposed for 10 months to tobacco smoke and/or UV light in vivo, and their effects on skin were investigated. Some biophysical parameters such as development of erythema, transepidermal water loss (TEWL), and skin elasticity were measured. The results show that UV and CS may be acting synergistically, as shown by the enhanced TEWL, erythema values, epitheliomas, and squamous cell carcinomas (SCCs) observed, whereas PBE seems to protect skin against SCC.


Subject(s)
Skin/drug effects , Skin/radiation effects , Tobacco Smoke Pollution/adverse effects , Ultraviolet Rays/adverse effects , Animals , Antioxidants/pharmacology , Carcinoma/etiology , Carcinoma, Squamous Cell/etiology , Elasticity , Erythema/etiology , Female , Flavonoids/pharmacology , Male , Melanins , Mice , Mice, Hairless , Plant Extracts , Sex Factors , Skin Neoplasms/etiology , Time Factors , Water Loss, Insensible/drug effects , Water Loss, Insensible/radiation effects
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