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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.
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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.
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Algoritmos , Retardo del Crecimiento Fetal/diagnóstico , Recién Nacido Pequeño para la Edad Gestacional , Ultrasonografía Prenatal , Adulto , Femenino , Humanos , Valor Predictivo de las Pruebas , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
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.
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Aspirina/uso terapéutico , Retardo del Crecimiento Fetal/prevención & control , Factor de Crecimiento Placentario/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Preeclampsia/prevención & control , Proteína Plasmática A Asociada al Embarazo/metabolismo , Arteria Uterina/diagnóstico por imagen , Adulto , Biomarcadores/sangre , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Tamizaje Masivo , Preeclampsia/diagnóstico , Valor Predictivo de las Pruebas , Embarazo , Primer Trimestre del Embarazo , Diagnóstico PrenatalRESUMEN
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.
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Preeclampsia/epidemiología , Diagnóstico Prenatal , Adulto , Algoritmos , Ensayos Clínicos como Asunto , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Guías de Práctica Clínica como Asunto , Preeclampsia/diagnóstico , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
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.
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Factor de Crecimiento Placentario/sangre , Preeclampsia/diagnóstico , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo/metabolismo , Medición de Riesgo/métodos , Arteria Uterina/fisiopatología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Presión Arterial/fisiología , Teorema de Bayes , Biomarcadores/sangre , Femenino , Edad Gestacional , Humanos , Embarazo , Estudios Prospectivos , Flujo Pulsátil/fisiologíaRESUMEN
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.
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Aspirina/uso terapéutico , Tamizaje Masivo/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Preeclampsia/diagnóstico , Preeclampsia/prevención & control , Arteria Uterina/diagnóstico por imagen , Adulto , Algoritmos , Biomarcadores/sangre , Método Doble Ciego , Femenino , Humanos , Factor de Crecimiento Placentario/sangre , Embarazo , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo/metabolismo , Estudios Prospectivos , Proyectos de Investigación , Adulto JovenRESUMEN
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.
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Biomarcadores/sangre , Guías de Práctica Clínica como Asunto , Preeclampsia/diagnóstico , Diagnóstico Prenatal , Femenino , Edad Gestacional , Humanos , Preeclampsia/sangre , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Curva ROC , Medición de Riesgo , Sociedades Médicas , Reino Unido , Estados UnidosRESUMEN
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.
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Inhibidores de la Aromatasa/uso terapéutico , Trastornos del Crecimiento/tratamiento farmacológico , Leuprolida/uso terapéutico , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Anastrozol , Estatura/efectos de los fármacos , Densidad Ósea , Estudios de Casos y Controles , Niño , Femenino , Estudios de Seguimiento , Hormona Liberadora de Gonadotropina/metabolismo , Grecia/epidemiología , Trastornos del Crecimiento/epidemiología , Humanos , Pronóstico , Estudios Prospectivos , Pubertad Precoz , Maduración Sexual/efectos de los fármacosRESUMEN
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.
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Síndrome de Hipersensibilidad a Medicamentos/etiología , Febuxostat/efectos adversos , Supresores de la Gota/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
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.
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Cartílago Articular/patología , Condrocitos/patología , Osteoartritis/patología , Ribonucleasa III/fisiología , Animales , Artritis Experimental/enzimología , Artritis Experimental/genética , Artritis Experimental/patología , Enfermedades del Desarrollo Óseo/enzimología , Enfermedades del Desarrollo Óseo/genética , Enfermedades del Desarrollo Óseo/patología , Muerte Celular/genética , Muerte Celular/fisiología , Femenino , Eliminación de Gen , Placa de Crecimiento/patología , Masculino , Ratones Noqueados , Ratones Transgénicos , MicroARNs/genética , Osteoartritis/enzimología , Osteoartritis/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/fisiología , Ribonucleasa III/deficiencia , Ribonucleasa III/genética , TamoxifenoRESUMEN
Acne vulgaris, a chronic inflammatory skin disease with a high prevalence worldwide, necessitates reliable preclinical models for both understanding its pathogenesis and evaluating potential anti-acne therapies. This study aims to establish a robust mouse model using intracutaneous injection of Cutibacterium acnes bacterial suspension. Three hairless mouse strains (SKH-hr1, SKH-hr2 brown, and SKH-hr2 + ApoE) were systematically compared to ascertain the stains most closely resembling acne in humans. Various assessments, including photo documentation, biophysical evaluation, blood analysis, and histopathology, were conducted. Despite all strains exhibiting acne-like lesions, SKH-hr1 mice emerged as the most suitable model, demonstrating the most satisfactory results across multiple criteria. This research underscores the significance of employing hairless mice strains as models in acne studies to enhance and facilitate the development of effective therapeutic interventions.
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Acné Vulgar , Modelos Animales de Enfermedad , Ratones Pelados , Animales , Acné Vulgar/microbiología , Ratones , Propionibacterium acnes , Femenino , Piel/microbiología , Piel/patología , Masculino , Propionibacteriaceae/patogenicidadAsunto(s)
Hemangioma/diagnóstico por imagen , Hemangioma/cirugía , Coagulación con Láser , Enfermedades Placentarias/cirugía , Complicaciones Neoplásicas del Embarazo/cirugía , Ultrasonografía Intervencional , Adulto , Femenino , Hemangioma/irrigación sanguínea , Humanos , Enfermedades Placentarias/diagnóstico por imagen , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico por imagen , Resultado del TratamientoRESUMEN
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.
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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.
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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.
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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.
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Arteria Celíaca , Arteria Hepática , Adulto , Angiografía , Aorta Abdominal/diagnóstico por imagen , Arteria Celíaca/diagnóstico por imagen , Femenino , Humanos , Arteria EsplénicaAsunto(s)
Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico por imagen , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico por imagen , Anciano , Diagnóstico Precoz , Humanos , Masculino , UltrasonografíaRESUMEN
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.
Asunto(s)
Metales Pesados/análisis , Olea , Eliminación de Residuos , Ceniza del Carbón , Incineración , SueloRESUMEN
Little is known about in vivo menisci loads and displacements in the knee during strenuous activities. A new method that combines high-speed kinematics measured with biplane dynamic Roentgen stereogrammetric analysis (DRSA) and a subject-specific finite element (FE) model for studying in vivo meniscal behavior is presented here. Further model calibration in a very controlled uniaxial low and high-rate compression loading condition is presented by comparing the model behavior against the measured high-accuracy menisci DRSA kinematics and direct tibio-femoral pressure measurement from a K-scan sensor. It is apparent that certain model aspects such as removing of the pressure sensor from the model can result in relatively large errors (14%) in contact parameters that are not reflected in the change of the measured meniscal kinematics. Changing mesh size to 1mm by 1mm elements increased the magnitude of all but one of the contact variables by up to 45%. This local validation using accurate localized patient-specific geometry and meniscal kinematics was needed to enhance model fidelity at the level of contact between menisci and cartilage.
Asunto(s)
Imagenología Tridimensional/métodos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiología , Meniscos Tibiales/fisiología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Adulto , Módulo de Elasticidad , Análisis de Elementos Finitos , Humanos , Masculino , Meniscos Tibiales/diagnóstico por imagen , Presión , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estrés MecánicoRESUMEN
Ceramides are the most important intercellular lipids of the stratum corneum, regulating the barrier function of the skin and participating as second signal messenger in stress-induced apoptosis. The high lipophilicity of ceramides presents a pharmacological problem. In order to overcome this problem two lipophilic delivery systems were used for the incorporation of the ceramides: (1) nanoemulsions (NE) and (2) solid lipid nanoparticles (SLN). The influence of the incorporation of ceramides on the particle shape, size and Polydispersity Index was investigated by photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). The results showed that NE can incorporate larger amounts of ceramides than SLN (up to 23.2% and 5% of lipid matrix, respectively) without any significant alteration on the morphology of the dispersed particles. The incorporation of higher amounts of ceramides into SLN, leads to anisometric platelet-like formations that are known to be caused by the transition of triglycerides from alpha- to beta-mesomorph. The results of this study can be useful for the design of appropriate delivery systems and for further pharmacological evaluations.