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Drinking water quality can be compromised by endocrine-disrupting chemicals (EDCs). Three phenolic compounds [bisphenol A (BPA), nonylphenol (NP), and 4-octylphenol (OP)] and three hormones [17ß-estradiol (E2), estrone (E1), and 17α-ethinylestradiol (EE2)] were analyzed as EDCs potentially occurring in source and drinking water from three full-scale drinking water treatment plants (DWTPs) in the Romagna area (Italy) by a combined approach of HPLC-MS/MS target analysis and effect-based tests for estrogenicity and genotoxicity. The EDC removal efficiency was evaluated at different steps along the treatment process in the most advanced DWTP. NP prevailed in all samples, followed by BPA. Sporadic contamination by OP and E1/E2 appeared only in the source waters; EE2 was never detected. No estrogenic or genotoxic activity was found, except for two samples showing estrogenicity well below the effect-based trigger value suggested for drinking water safety (0.9 ng/L EEQ). BPA and NP levels were largely below the threshold value; however, increases were observed after the intermediate steps of the treatment chain. The good quality of the water relied on the last step, i.e. the activated carbon filtration. DWTPs may represent an extra source of EDCs and monitoring chemical occurrence at all steps of the process is advisable to improve efficiency.
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The rapid expansion of home health care has raised many unresolved issues and will have far-reaching consequences that can only be overcome with a holistic approach to help build and use collective intelligence in a structured, systemic way to anticipate developments. In this frame, the set of issues covered by the human factors research field will significantly impact the safety, quality, and effectiveness of home health care. However, only with a gaze of strategic foresight will we be capable of exploring, anticipating, and shaping the future. A group of researchers from the Italian Society of Ergonomics and Human Factors (SIE) has developed a road map to help all the stakeholders involved in this process.
A Strategic Foresight study was conducted to define a preferred scenario of home care in the next 20 years. A hybrid survey method called Human-Centred Foresight was applied. The results achieved in the study show a possible scenario of home care that can define medium- and long-term goals from today until 2041.
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OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 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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Placenta Accreta , Placenta Previa , Cesárea , Femenino , Humanos , Placenta/diagnóstico por imagen , Placenta/patología , Placenta Accreta/diagnóstico por imagen , Placenta Accreta/patología , Placenta Previa/diagnóstico por imagen , Placenta Previa/patología , Embarazo , Tercer Trimestre del Embarazo , Diagnóstico Prenatal , Estudios Prospectivos , Estudios Retrospectivos , Ultrasonografía Prenatal/métodosRESUMEN
AIM: To identify, in vitro, the best fruit juice to use as oral contrast agent in magnetic resonance cholangiopancreatography (MRCP) and to test, in vivo, the best natural juice and the new parameters in MRCP sequences identified in vitro. MATERIALS AND METHODS: The in vitro evaluations consisted of measuring the T2 values of a pure solution of manganese (Mn) and iron (Fe) at different concentrations, measuring the content of Mn and Fe in five commercial juices and their T2 relaxation times, and identifying the optimal juice dilution for suppressing the gastrointestinal fluid signal. The new parameters of MRCP sequences were tested in vivo. RESULTS: Manganese alone strongly influenced the shortening of the T2 values (p=0.004). The T2 value with an echo time (TE) of ≥1,000 ms enabled sufficient intestinal fluid suppression in the case of high juice dilution. A flip angle of 90° maximised the differences between the high signal from static fluids, such as the bile and the fluid in the gastrointestinal tract, using fast imaging employing steady-state acquisition (FIESTA) sequences (p<0.001). CONCLUSION: The shortening of the T2 relaxation time depended only on the Mn concentration. All the commercial juices had an Mn concentration sufficient to suppress the gastrointestinal fluid signal using long TE sequences. The oral ingestion of commercial juice before MRCP was enough to suppress the signal from the gastrointestinal fluids, regardless of its dilution after ingestion. When using FIESTA sequences, a flip angle of 90° allowed the best suppression of gastrointestinal fluid signals.
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Pancreatocolangiografía por Resonancia Magnética/métodos , Medios de Contraste/administración & dosificación , Jugos de Frutas y Vegetales , Administración Oral , Medios de Contraste/química , Humanos , Técnicas In Vitro , Hierro/química , Manganeso/químicaRESUMEN
BACKGROUND: Metal plates are the fixation devices used most frequently to proximal humeral fractures (PHFs). However, in recent years carbon fiber-reinforced polyetheretherketone (CFR-PEEK) plates have become increasingly common. This study compares the clinical and radiographic outcomes of 42 Neer three- and four-part PHFs treated with CFR-PEEK or metal (titanium) plates. MATERIALS AND METHODS: Forty-two PHF patients were managed with CFR-PEEK plates (n = 21, males/females 9/12; mean age 57.4 years; mean follow-up 30.7 months; CFR-PEEK group) or metal plates (n = 21; males/females 7/14; mean age 55.8 years; mean follow-up 52.7 months; Metal group). Active shoulder mobility (anterior elevation, lateral elevation, external rotation, and internal rotation), the Constant-Murley Score, the Simple Shoulder Test Score, and the pain score were recorded. Preoperative computed tomography scans and X-rays were obtained. Postoperative fracture healing and displacement, tuberosity resorption and/or malposition, hardware position, and cortical thinning (CT) under the plate were assessed radiographically. RESULTS: Shoulder mobility, clinical, and pain scores were similar in both patient groups. CT was significantly greater in CFR-PEEK patients (mean difference, 1.14 mm; p = 0.0003). In both groups, incomplete or poor calcar reduction was associated to a significantly higher complication rate, especially stiffness and muscle weakness (p = 0.016). The rate of tuberosity resorption was significantly higher in the Metal group (p = 0.040). Two patients required revision to a hemiarthroplasty (CFR-PEEK) and reverse arthroplasty (Metal group). CONCLUSIONS: CFR-PEEK plates provide a viable alternative to conventional titanium plates in PHFs, ensuring similar clinical outcomes and a lower rate of tuberosity resorption, but they involve higher stress shielding under the plate.
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Placas Óseas , Fibra de Carbono , Cetonas , Polietilenglicoles , Fracturas del Hombro/cirugía , Titanio , Adulto , Anciano , Benzofenonas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polímeros , Diseño de Prótesis , Estudios Retrospectivos , Fracturas del Hombro/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Muscle quality is defined as the force generated by each volumetric unit of muscle tissue. No consensus exists on an optimal measure of muscle quality, impeding comparison across studies and implementation in clinical settings. It is unknown whether muscle quality measures that rely on complex and expensive tests, such as isokinetic dynamometry and computerized tomography correlate with lower extremity performance (LEP) any better than measures derived from simpler and less expensive tests, such as grip strength (Grip) and appendicular lean mass (ALM) assessed by DXA. Additionally, whether muscle quality is more strongly associated with LEP than strength has not been fully tested. OBJECTIVES: This study compares the concurrent validity of alternative measures of muscle quality and characterizes their relationship with LEP. We also whether muscle quality correlates more strongly with LEP than strength alone. DESIGN: Cross-sectional analysis. SETTING: Community. PARTICIPANTS: 365 men and 345 women 65 years of age and older in the Baltimore Longitudinal Study of Aging. MEASURES: Thigh cross-sectional area (TCSA), isokinetic and isometric knee extension strength (ID), BMI adjusted ALM (ALMBMI) from DXA, and Grip. Concurrent validity was assessed as the percent variance of different measures of LEP explained by each muscle quality measure. In addition, we compared LEP relationships between each measure of strength and its correspondent value of muscle quality. Confidence intervals for differences in percent variance were calculated by bootstrapping. RESULTS: Grip/ALMBMI explained as much variance as ID/TCSA across all LEP measures in women and most in men. Across all LEP measures, strength explained as much variance of LEP as muscle quality. CONCLUSIONS: Grip/ALMBMI and ID/TCSA measures had similar correlations with LEP. Muscle quality did not outperform strength. Although evaluating muscle quality may be useful to assess age-related mechanisms of change in muscle strength, measures of strength alone may suffice to understand the relationship between muscle and LEP.
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Ejercicio Físico , Anciano Frágil/estadística & datos numéricos , Extremidad Inferior/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Evaluación Geriátrica/métodos , Humanos , Estudios Longitudinales , Masculino , Análisis de Regresión , Características de la ResidenciaRESUMEN
Landscape genetics aims to investigate functional connectivity among wild populations by evaluating the impact of landscape features on gene flow. Genetic distances among populations or individuals are generally better explained by least-cost path (LCP) distances derived from resistance surfaces than by simple Euclidean distances. Resistance surfaces reflect the cost for an organism to move through particular landscape elements. However, determining the effects of landscape types on movements is challenging. Because of a general lack of empirical data on movements, resistance surfaces mostly rely on expert knowledge. Habitat-suitability models potentially provide a more objective method to estimate resistance surfaces than expert opinions, but they have rarely been applied in landscape genetics so far. We compared LCP distances based on expert knowledge with LCP distances derived from habitat-suitability models to evaluate their performance in landscape genetics. We related all LCP distances to genetic distances in linear mixed effect models on an empirical data set of wolves (Canis lupus) from Italy. All LCP distances showed highly significant (P ≤ 0.0001) standardized ß coefficients and R 2 values, but LCPs from habitat-suitability models generally showed higher values than those resulting from expert knowledge. Moreover, all LCP distances better explained genetic distances than Euclidean distances, irrespective of the approaches used. Considering our results, we encourage researchers in landscape genetics to use resistance surfaces based on habitat suitability which performed better than expert-based LCPs in explaining patterns of gene flow and functional connectivity.
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Ecosistema , Genética de Población , Flujo Génico , Modelos Lineales , Modelos TeóricosRESUMEN
The return of the wolf in its historical range is raising social conflicts with local communities for the perceived potential threat to people safety. In this study we applied molecular methods to solve an unusual case of wolf attack towards a man in the Northern Italian Apennines. We analysed seven biological samples, collected from the clothes of the injured man, using mtDNA sequences, the Amelogenin gene, 39 unlinked autosomal and four Y-linked microsatellites. Results indicated that the aggression was conducted by a male dog and not by a wolf nor a wolf x dog hybrid. Our findings were later confirmed by the victim, who confessed he had been attacked by the guard dog of a neighbour. The genetic profile of the owned dog perfectly matched with that identified from the samples previously collected. Our results prove once again that the wolf does not currently represent a risk for human safety in developed countries, whereas most animal aggressions are carried out by its domestic relative, the dog.
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Mordeduras y Picaduras , Dermatoglifia del ADN , ADN Mitocondrial/genética , Perros/genética , Especificidad de la Especie , Lobos/genética , Amelogenina/genética , Animales , Vestuario , Humanos , Masculino , Repeticiones de Microsatélite , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. MATERIALS AND METHODS: To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. RESULTS: At the end of the enrollment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%-99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. CONCLUSIONS: The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.
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Neoplasias de la Mama/patología , Carcinoma/patología , Colorantes Fluorescentes , Verde de Indocianina , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Carcinoma/cirugía , Estudios de Cohortes , Femenino , Humanos , Mastectomía/métodos , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Estudios Prospectivos , Radiofármacos , Agregado de Albúmina Marcado con Tecnecio Tc 99mRESUMEN
In this work, high surface area antimony doped tin oxide (Sb-SnO2) has been synthesized using a modified sol-gel synthesis method. The bulk and surface properties of the metal oxide support have been investigated as a function of the processing conditions. A change in the Sb-SnO2 processing conditions, while preserving an overall invariant bulk composition, led to substantial modification of the surface stoichiometry. Accelerated stability test protocols have shown that the surface composition represents a crucial parameter for the electrochemical stability of Sb-SnO2. Model Pt/Sb-SnO2 electrodes have been developed depositing Pt nanoparticles by magnetron sputtering on the optimized Sb-SnO2 porous surface. A significant enhancement in the corrosion stability upon 1000 potential cycles between 0.5 and 1.5 V (RHE) at 50 mV s(-1) has been observed for the Pt/Sb-SnO2 system compared to Pt/carbon.
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The presence of pharmaceuticals in the environment is now a major concern given their potential adverse effects on organisms, particularly human beings. Because the feeding style and habitat of the crab Carcinus maenas make this species vulnerable to organic contaminants, it has been used previously in ecotoxicological studies. Lysosomal membrane stability (LMS) in crabs is a general indicator of cellular well-being and can be visualized by the neutral red retention (NRR) assay. LMS in crab hemolymph has been evaluated as a cellular biomarker of adverse effects produced by exposure to pharmaceutical compounds. Crabs were exposed in the laboratory to four different pharmaceuticals for 28 days in a semistatic 24-h renewal assay. Filtered seawater was spiked every 2 days with various concentrations (from 0.1 to 50 µg · L(-1)) of caffeine, ibuprofen, carbamazepine, and novobiocin. Results showed that NRR time, measured at day 28, was significantly reduced (p < 0.05) after exposure to environmental concentrations of each pharmaceutical (caffeine = 15 µg · L(-1); carbamazepine = 1 µg · L(-1); ibuprofen = 5 µg · L(-1); and novobiocin = 0.1 µg · L(-1)) when compared with control organisms. The predicted "no environmental effect" concentration/measured environmental concentration results showed that the selected pharmaceuticals are toxic at environmental concentrations and need further assessment. LMS monitoring in crabs is a sensitive tool for evaluating exposure to concentrations of selected drugs under laboratory conditions and provides a robust tier 1 testing approach (screening biomarker) for rapid assessment of marine pollution and environmental impact assessments for analyzing pharmaceutical contamination in aquatic environments.
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Braquiuros/fisiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Monitoreo del Ambiente/métodos , Lisosomas , Contaminantes Químicos del Agua/toxicidad , Animales , Biomarcadores/metabolismo , Hemolinfa/química , Preparaciones Farmacéuticas/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
PURPOSE: Digital radiography technology has replaced conventional screen-film systems in many hospitals. Despite the different characteristics of new detector materials, frequently, the same radiological protocols previously optimised for screen film are still used with digital equipment without any critical review. This study addressed optimisation of exposure settings for chest examinations with digital systems, considering both image quality and patient dose. MATERIALS AND METHODS: Images acquired with direct digital radiography equipment and a computed radiography system were analysed with specially developed commercial software with a four-alternative forced-choice method: the most promising protocols were then scored by two senior radiologists. RESULTS: Digital technology offers a wide dynamic range and the ability to postprocess images, allowing use of lower tube potentials in chest examinations. The computed radiography system showed both better image quality and lower dose at lower energies (85 kVp and 95 kVp) than those currently used (125 kVp). Direct digital radiography equipment confirmed both its superior image quality and lower dose requirements compared with the storage phosphor plate system. CONCLUSIONS: Generally, lowering tube potentials in chest examinations seems to allow better image quality/effective dose ratio when using digital equipment.
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Protocolos Clínicos/normas , Intensificación de Imagen Radiográfica/normas , Radiografía Torácica/normas , Tomografía Computarizada por Rayos X/normas , Diseño de Equipo , Humanos , Fantasmas de Imagen , Dosis de Radiación , Intensificación de Imagen Radiográfica/instrumentación , Interpretación de Imagen Radiográfica Asistida por Computador , Radiografía Torácica/instrumentación , Reproducibilidad de los Resultados , Programas Informáticos , Pantallas Intensificadoras de Rayos XRESUMEN
Posttraumatic wounds of the lower leg with soft tissue defects and exposed fractures are a reconstructive challenge due to the scarce availability of local tissues and recipient vessels. Even when a free tissue transfer can be performed the risk of failure remains considerable. When a free flap is contraindicated or after a free flap failure, the cross-leg flap is still nowadays a possible option. We report a case of a male with a severe posttraumatic wound of the lower leg with exposed tibia fracture firstly treated with two consecutive latissimus dorsi muscular free flaps, failed for vascular thrombosis; the coverage was then achieved with a cross-leg flap with acceptable results.
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Cholinesterase (ChE) activities were characterized in silver European eel, Anguilla anguilla, grown in the brackish lagoon of Comacchio (Italy). All specimens were harvested at the "lavoriero", a traditional eel trapping weir that captures eels while leaving internal waters at the onset of reproductive migration. To our knowledge, no investigation on ChE was reported in silver eels. Therefore a first characterization of enzyme activity in muscle, brain, liver and plasma of silver eel was carried out, in the presence of different substrates, selective inhibitors, and four pesticides representative of the carbamate and organophosphate classes. Brain and white skeletal muscle showed similar ChE activities, 5- and 10-fold higher than those detected in liver and plasma, respectively. Km values of 0.31 and 0.30 mM, and Vmax values of 40.28 and 35.47 nmol min(-1) mg protein(-1) were obtained in brain and muscle ChE, respectively. Acetycholinesterase was the predominant ChE form in all tissues, as concluded by comparing the effects of BW 284c51, iso-OMPA and eserine. ChE activities in brain and muscle were significantly inhibited by in vitro treatment with pesticides, with the following order of potency: carbofuran>carbaryl>chlorpyrifos≥diazinon.
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Encéfalo/enzimología , Colinesterasas/efectos de los fármacos , Colinesterasas/metabolismo , Hígado/enzimología , Músculo Esquelético/enzimología , Plaguicidas/farmacología , Anguilla , Animales , Bencenamina, 4,4'-(3-oxo-1,5-pentanodiil)bis(N,N-dimetil-N-2-propenil-), Dibromuro/farmacología , Inhibidores de la Colinesterasa/farmacología , Colinesterasas/sangre , Cinética , Fisostigmina/farmacología , Tetraisopropilpirofosfamida/farmacologíaRESUMEN
Connexins (Cx) are membrane proteins able to influence cell trophoblast responses, such as proliferation, differentiation, migration and invasiveness. Likewise, glucocorticoids are also known to modulate many factors involved in implantation, including trophoblast gap-junction intercellular communication, although their influence on pregnancy is controversial. In order to investigate the effects of betamethasone, a synthetic glucocorticoid, on Cx and glucocorticoid receptor (GR) expression and localisation, as well as on cell proliferation, the extravillous trophoblast-derived HTR-8/SVneo cell line was used as a model. The results, confirmed by means of immunofluorescence, demonstrate that betamethasone selectively modifies GR and Cx expression, enhancing the GRα isoform without affecting GRß, and inhibiting Cx40 expression whilst increasing that of Cx43 and Cx45. Furthermore, betamethasone was shown to exert an inhibitory action on cell proliferation. In this model the abortion drug RU-486 (mifepristone), reported to be a GR antagonist, did not counteract this effect of betamethasone. On the contrary, it induced responses similar to those of the hormone. Knowing that RU-486 is also a potent progesterone-receptor antagonist, the effect of progesterone alone and in combination with the drug on Cx expression and cell proliferation was then tested. Progesterone showed the same effect as betamethasone on Cx expression, but it did not affect proliferation. Based on these results, neither the abortion effects of RU-486 nor the protective action of betamethasone and progesterone are exerted by modulation of Cx. RU-486 did not antagonise the progesterone effect, suggesting that its abortive action does not involve alteration of trophoblast Cx expression.
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Abortivos Esteroideos/farmacología , Betametasona/farmacología , Conexinas/genética , Mifepristona/farmacología , Progesterona/farmacología , Trofoblastos/metabolismo , División Celular/efectos de los fármacos , Línea Celular , Conexina 43/análisis , Conexina 43/genética , Conexinas/análisis , Técnica del Anticuerpo Fluorescente Indirecta , Expresión Génica/efectos de los fármacos , Glucocorticoides/farmacología , Humanos , Receptores de Glucocorticoides/análisis , Receptores de Glucocorticoides/genética , Trofoblastos/química , Trofoblastos/citología , Proteína alfa-5 de Unión ComunicanteRESUMEN
OBJECTIVE: To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV). DESIGN: Retrospective observational study. SETTING: Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy. POPULATION: HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995-2009. METHODS: Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection. MAIN OUTCOME MEASURES: A statistical analysis was performed to determine the value of each parameter in predicting outcome. RESULTS: Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were ß(2) -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. ß(2) -Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy. CONCLUSIONS: The determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.
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Infecciones por Citomegalovirus/congénito , Sangre Fetal/virología , Enfermedades Fetales/diagnóstico , Complicaciones Infecciosas del Embarazo/diagnóstico , Biomarcadores/sangre , Infecciones por Citomegalovirus/diagnóstico , Diagnóstico Precoz , Femenino , Humanos , Recién Nacido , Embarazo , Atención Prenatal/métodos , Pronóstico , Estudios Retrospectivos , Microglobulina beta-2/sangreRESUMEN
A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.
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Antineoplásicos/química , Antineoplásicos/farmacología , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Naftalenos/farmacología , Fotones , Sulfonamidas/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/síntesis química , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Naftalenos/síntesis química , Naftalenos/química , Estereoisomerismo , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/químicaRESUMEN
The aim of this work was to provide a greater insight into the possible effects of Cd on signal transduction and stress-related pathways in reproductive tissues. Cd is a known placental toxin in both animals and humans. Our experiments were designed to study the influence of Cd on MAPK (ERK1/2, JNK1/2 and p38MAPK) activation in the extravillous trophoblast cell line, HTR-8/SVneo, used as an experimental model. We also studied the HSP70 response in cells exposed to Cd, since these proteins may have an important role in conferring protection and tolerance against teratogenic concentrations of the metal. The effects of Cd were compared with those of a well-known toxic agent, H2O2. The metal triggered MAPK activation in a dose- and time-dependent manner. At 30 microM Cd, stimulations of about 300%, 550% and 250% were observed for ERK1/2, JNK1/2, and p38MAPK, respectively. Phosphorylation of ERK1/2 and JNK1/2 was significantly induced after a 1-h exposure to 30 microM Cd, while that of p38MAPK occurred only after 8h. Similarly, H2O2 caused dose- and time-dependent activation of MAPK pathways. Cd potently stimulated HSP70 expression and that of related genes HSP70 A, B and C. H2O2 did not increase HSP70 and HSP70 A and B expression, while temporarily increasing HSP70C transcript levels. In conclusion, Cd triggers different stress responses in trophoblast cells involving HSP70 and SAPK, and also enhances ERK1/2 phosphorylation. Since MAPK dependent pathways play a crucial role during pregnancy, non-physiological activation by Cd exposure may disrupt normal functions in trophoblast cells.