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The relationship between exposure to air pollutants and fetal growth outcomes has shown inconsistency, and only a limited number of studies have explored the impact of air pollution on gestational hypertension and birth outcomes. This study aimed to evaluate how maternal exposure to air pollutants and blood pressure could influence fetal birth outcomes. A total of 55 women with gestational hypertension and 131 healthy pregnant women were enrolled in this study. Data pertaining to personal characteristics, prenatal examinations, outdoor air pollutant exposure, and fetal birth outcomes were collected. The study revealed that fetal birth weight and abdominal circumference exhibited a significant reduction among women with gestational hypertension compared to healthy pregnant women, even after adjustments for body mass index, gestational age, and exposure to air pollutants had been made. Moreover, maternal exposure to outdoor air pollutants displayed a notable correlation with decreased birth length of fetuses. Consequently, the study concluded that maternal blood pressure and exposure to outdoor air pollutants during pregnancy potentially stand as pivotal factors influencing fetal birth outcomes.
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Contaminantes Atmosféricos , Contaminación del Aire , Hipertensión Inducida en el Embarazo , Exposición Materna , Humanos , Embarazo , Femenino , Adulto , Contaminación del Aire/efectos adversos , Peso al Nacer , Resultado del Embarazo , Recién NacidoRESUMEN
OBJECTIVE: Neonatal hypoxic-ischemic brain damage (HIBD) can have long-term implications on patients' physical and mental health, yet the available treatment options are limited. Recent research has shown that low-intensity pulsed ultrasound (LIPUS) holds promise for treating neurodegenerative diseases and traumatic brain injuries. Our objective was to explore the therapeutic potential of LIPUS for HIBD. METHODS: Due to the lack of a suitable animal model for neonatal HIBD, we will initially simulate the therapeutic effects of LIPUS on neuronal cells under oxidative stress and neuroinflammation using cell experiments. Previous studies have investigated the biologic responses following intracranial injection of 6-hydroxydopamine (6-OHDA). In this experiment, we will focus on the biologic effects produced by LIPUS treatment on neuronal cells (specifically, SH-SY5Y cells) without the presence of other neuroglial cell assistance after stimulation with 6-OHDA. RESULTS: We found that (i) pulsed ultrasound exposure, specifically three-intermittent sonication at intensities ranging from 0.1 to 0.5 W/cm², did not lead to a significant decrease in viability among SH-SY5Y cells; (ii) LIPUS treatment exhibited a positive effect on cell viability, accompanied by an increase in glial cell-derived neurotrophic factor (GDNF) levels and a decrease in caspase three levels; (iii) the administration of 6-OHDA had a significant impact on cell viability, resulting in a decrease in both brain cell-derived neurotrophic factor (BDNF) and GDNF levels, while concurrently elevating caspase three and matrix metalloproteinase-9 (MMP-9) levels; and (iv) LIPUS treatment demonstrated its potential to alleviate the changes induced by 6-OHDA, particularly in the levels of BDNF, GDNF, and tyrosine hydroxylase (TH). CONCLUSION: LIPUS treatment may possess partial therapeutic capabilities for SH-SY5Y cells damaged by 6-OHDA neurotoxicity. Our findings enhance our understanding of the effects of LIPUS treatment on cell viability and its modulation of key factors involved in the pathophysiology of HIBD and show the promising potential of LIPUS as an alternative therapeutic approach for neonates with HIBD.
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Productos Biológicos , Neuroblastoma , Animales , Recién Nacido , Humanos , Factor Neurotrófico Derivado del Encéfalo , Oxidopamina , Factor Neurotrófico Derivado de la Línea Celular Glial , Ondas Ultrasónicas , CaspasasRESUMEN
ATP-binding cassette (ABC) transporters, notably ABCB1 (P-glycoprotein) and ABCG2, play a crucial role in the development of multidrug resistance (MDR) during the administration of chemotherapy for cancer patients. With a lack of approved treatments for addressing multidrug-resistant cancers, MDR remains a substantial challenge to the effective management of cancer. Rather than focusing on developing novel synthetic inhibitors, a promising approach to combat MDR involves repurposing approved therapeutic agents to enhance the sensitivity to cytotoxic antiproliferative drugs of multidrug-resistant cancer cells with high expression of ABCB1 or ABCG2. In this investigation, we observed a substantial reversal of MDR conferred by ABCB1 and ABCG2 in multidrug-resistant cancer cells through the use of mobocertinib, an approved third-generation inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Mobocertinib demonstrated the ability to hinder drug transport function without causing changes in protein expression. The interactions between mobocertinib and ABCB1, as well as ABCG2, were validated through ATPase assays. Furthermore, in silico docking simulations were utilized to substantiate the binding of mobocertinib within the drug-binding pockets of both ABCB1 and ABCG2. We conclude that further testing of mobocertinib in combination therapy is warranted for patients with tumors expressing elevated levels of the ABC drug transporters ABCB1 and ABCG2.
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The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2.
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ATP-binding cassette transporters, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in cancer patients undergoing conventional chemotherapy. The absence of approved therapeutic agents for multidrug-resistant cancers presents a significant challenge in effectively treating cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether furmonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters. Furmonertinib stands out due to its ability to inhibit drug transport without affecting protein expression. The discovery of this characteristic was validated through ATPase assays, which revealed interactions between furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of furmonertinib offered insights into potential interaction sites within the drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed drug. Given the encouraging results, we propose that furmonertinib should be explored as a potential candidate for combination therapy in patients with tumors that have high levels of ABCB1 and/or ABCG2. This combination therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in cancer treatment.
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Systemic inflammation is associated with intestinal inflammation and neuroinflammation by imbalancing the gut-brain axis. Low-intensity pulsed ultrasound (LIPUS) has neuroprotective and anti-inflammatory effects. This study explored LIPUS's neuroprotective effects against lipopolysaccharide (LPS)-induced neuroinflammation through transabdominal stimulation. Male C57BL/6J mice were intraperitoneally injected with LPS (0.75 mg/kg) daily for seven days, and abdominal LIPUS was applied to the abdominal area for 15 min/day during the last six days. One day after the last LIPUS treatment, biological samples were collected for microscopic and immunohistochemical analysis. Histological examination showed that LPS administration leads to tissue damage in the colon and brain. Transabdominal LIPUS stimulation attenuated colonic damage, reducing histological score, colonic muscle thickness, and villi shortening. Furthermore, abdominal LIPUS reduced hippocampal microglial activation (labeled by ionized calcium-binding adaptor molecule-1 [Iba-1]) and neuronal cell loss (labeled by microtubule-associated protein 2 [MAP2]). Moreover, abdominal LIPUS attenuated the number of apoptotic cells in the hippocampus and cortex. Altogether, our results indicate that abdominal LIPUS stimulation attenuates LPS-induced colonic inflammation and neuroinflammation. These findings provide new insights into the treatment strategy for neuroinflammation-related brain disorders and may facilitate method development through the gut-brain axis pathway.
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Lipopolisacáridos , Neuroprotección , Animales , Ratones , Masculino , Lipopolisacáridos/toxicidad , Enfermedades Neuroinflamatorias , Ratones Endogámicos C57BL , Inflamación/inducido químicamente , Inflamación/terapia , Inflamación/metabolismoRESUMEN
Constitutive activation of the phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is crucial for tumor growth and progression. As such, this pathway has been an enticing target for drug discovery. Although HS-173 is a potent PI3K inhibitor that halts cancer cell proliferation via G2/M cell cycle arrest, the resistance mechanisms to HS-173 have not been investigated. In this study, we investigated the susceptibility of HS-173 to efflux mediated by the multidrug efflux transporters ABCB1 and ABCG2, which are two of the most well-known ATP-binding cassette (ABC) transporters associated with the development of cancer multidrug resistance (MDR). We found that the overexpression of ABCB1 or ABCG2 significantly reduced the efficacy of HS-173 in human cancer cells. Our data show that the intracellular accumulation of HS-173 was substantially reduced by ABCB1 and ABCG2, affecting G2/M arrest and apoptosis induced by HS-173. More importantly, the efficacy of HS-173 in multidrug-resistant cancer cells could be recovered by inhibiting the drug-efflux function of ABCB1 and ABCG2. Taken together, our study has demonstrated that HS-173 is a substrate for both ABCB1 and ABCG2, resulting in decreased intracellular concentration of this drug, which may have implications for its clinical use.
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Resistencia a Múltiples Medicamentos , Neoplasias , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Apoptosis , Resistencia a Antineoplásicos , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular , Transportadoras de Casetes de Unión a ATP/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Neoplasias/tratamiento farmacológico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Proteínas de Neoplasias/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATPRESUMEN
No consistent results from past studies have been found on the relationship between the effects of air pollutant exposure, preterm birth (PTB) and low birth weight (LBW) in fetuses. This study aimed to analyze the impact of high concentrations of air pollutants on the health outcomes of fetuses, especially regarding PTB and LBW. This study used keywords related to air pollutants, pregnancy, and birth outcomes, to search the literature within the databases of the Cochrane Library, PubMed, and Embase, which were published as of July 26, 2022. A total of 24 studies were included in this meta-analysis. This meta-analysis revealed that nitrogen dioxide (NO2) exposure throughout pregnancy was associated with an increased risk of PTB. Maternal exposure to PM2.5 (particulate matter sized less than 2.5 µm) during gestation was associated with the risk of LBW. The findings of this meta-analysis provide an important foundation for evaluating the relationship between exposure of air pollutants and fetal birth outcomes in countries with severe air pollution in the future.
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Contaminantes Atmosféricos , Contaminación del Aire , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/inducido químicamente , Exposición Materna , Dióxido de Nitrógeno/análisis , Recién Nacido de Bajo Peso , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Material Particulado/análisis , Peso al NacerRESUMEN
Studies often use the Edinburgh Postnatal Depression Scale (EPDS) or the Beck Depression Inventory-II (BDI-II) as a screening tool for depression in new mothers or fathers following the birth of an infant, but no studies have evaluated EPDS as a predictor of postnatal depression for new fathers in a Chinese population. This study aimed to test the validity and reliability of a Chinese version of the EPDS for fathers of newborns in Taiwan. The study included 368 parents with newborns ≤2 months of age and without any health problems. Construct and criterion-related validities were assessed and Cronbach's alpha was used for measuring internal consistency reliability. The receiver operating characteristic (ROC) curve analyzed the optimal cutoff score for the EPDS. Scores for the Chinese EPDS were significantly higher for fathers who were >34 years of age, employed in a professional occupation, and participated in feeding their infant (p < .05). Mean scores among the fathers for the EPDS and BDI-II were significantly correlated (r = .64, p < .001). The Cronbach's alpha was .83 for the EPDS; ROC curve analysis revealed the optimal cutoff of the EPDS was ≥8 points and the area under the ROC curve was 0.91. The EPDS had good validity and reliability and should therefore be considered suitable for the evaluation of postnatal depression in fathers of newborn infants in Taiwan.
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Depresión Posparto , Recién Nacido , Femenino , Humanos , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Reproducibilidad de los Resultados , Psicometría , Escalas de Valoración Psiquiátrica , ChinaRESUMEN
Hydroxygenkwanin, a flavonoid isolated from the leaves of the Daphne genkwa plant, is known to have pharmacological properties; however, its modulatory effect on multidrug resistance, which is (MDR) mediated by ATP-binding cassette (ABC) drug transporters, has not been investigated. In this study, we examine the interaction between hydroxygenkwanin, ABCB1, and ABCG2, which are two of the most well-characterized ABC transporters known to contribute to clinical MDR in cancer patients. Hydroxygenkwanin is not an efflux substrate of either ABCB1 or ABCG2. We discovered that, in a concentration-dependent manner, hydroxygenkwanin significantly reverses ABCG2-mediated resistance to multiple cytotoxic anticancer drugs in ABCG2-overexpressing multidrug-resistant cancer cells. Although it inhibited the drug transport function of ABCG2, it had no significant effect on the protein expression of this transporter in cancer cells. Experimental data showing that hydroxygenkwanin stimulates the ATPase activity of ABCG2, and in silico docking analysis of hydroxygenkwanin binding to the inward-open conformation of human ABCG2, further indicate that hydroxygenkwanin sensitizes ABCG2-overexpressing cancer cells by binding to the substrate-binding pocket of ABCG2 and attenuating the transport function of ABCG2. This study demonstrates the potential use of hydroxygenkwanin as an effective inhibitor of ABCG2 in drug combination therapy trials for patients with tumors expressing higher levels of ABCG2.
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Antineoplásicos , Neoplasias , Humanos , Resistencia a Múltiples Medicamentos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Resistencia a Antineoplásicos , Proteínas de Neoplasias/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Flavonoides/farmacología , Transportadoras de Casetes de Unión a ATP/metabolismo , Neoplasias/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study investigated the effects of mobile health application designed based on mindfulness and social support theory on parenting self-efficacy and postpartum depression symptoms of puerperae. METHODS: We recruited 130 puerperae from a hospital in China and randomized them to an App use group (n = 65) and a waiting control group (n = 65). The App group underwent an 8-week app use intervention while the control group underwent no intervention. We measured four main variables (mindfulness, perceived social support, maternal parental self-efficacy and postpartum depressive symptoms) before and after the App use intervention. RESULTS: In the App group, perceived social support, maternal parental self-efficacy were significantly higher and postpartum depressive symptoms was significantly lower. In the control group, there were no significant differences in any of the four variables between the pre-test and post-test. CONCLUSIONS: Our findings indicated that the mobile health application may help to improve perceived social support, maternal self-efficacy and reduce postpartum depressive symptoms. The finding of the mobile health application's effect extends our understanding of integrative effects of mindfulness and perceived social support on reduction of postpartum depressive symptoms and suggests clinical potentials in the treatment of postpartum depressive symptoms.
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Depresión Posparto , Atención Plena , Aplicaciones Móviles , Telemedicina , Depresión , Depresión Posparto/terapia , Femenino , Humanos , Responsabilidad Parental , Apoyo SocialRESUMEN
The development of multidrug resistance (MDR) is one of the major challenges in the treatment of cancer which is caused by the overexpression of the ATP-binding cassette (ABC) transporters ABCB1 (P-glycoprotein) and/or ABCG2 (BCRP/MXR/ABCP) in cancer cells. These transporters are capable of reducing the efficacy of cytotoxic drugs by actively effluxing them out of cancer cells. Since there is currently no approved treatment for patients with multidrug-resistant tumors, the drug repurposing approach provides an alternative route to identify agents to reverse MDR mediated by ABCB1 and/or ABCG2 in multidrug-resistant cancer cells. WDR5-0103 is a histone H3 lysine 4 (H3K4) methyltransferase inhibitor that disrupts the interaction between the WD repeat-containing protein 5 (WDR5) and mixed-lineage leukemia (MLL) protein. In this study, the effect of WDR5-0103 on MDR mediated by ABCB1 and ABCG2 was determined. We found that in a concentration-dependent manner, WDR5-0103 could sensitize ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to conventional cytotoxic drugs. Our results showed that WDR5-0103 reverses MDR and improves drug-induced apoptosis in multidrug-resistant cancer cells by inhibiting the drug-efflux function of ABCB1 and ABCG2, without altering the protein expression of ABCB1 or ABCG2. The potential sites of interactions of WDR5-0103 with the drug-binding pockets of ABCB1 and ABCG2 were predicted by molecular docking. In conclusion, the MDR reversal activity of WDR5-0103 demonstrated here indicates that it could be used in combination therapy to provide benefits to a subset of patients with tumor expressing high levels of ABCB1 or ABCG2.
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Antineoplásicos , Neoplasias , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportadoras de Casetes de Unión a ATP , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Simulación del Acoplamiento Molecular , Proteínas de Neoplasias/metabolismo , Repeticiones WD40RESUMEN
The overexpression of ATP-binding cassette (ABC) transporter ABCB1 (P-glycoprotein) or ABCG2 (BCRP/MXR/ABCP) in cancer cells is frequently associated with the development of multidrug resistance (MDR) in cancer patients, which remains a major obstacle to effective cancer treatment. By utilizing energy derived from ATP hydrolysis, both transporters have been shown to reduce the chemosensitivity of cancer cells by actively effluxing cytotoxic anticancer drugs out of cancer cells. Knowing that there are presently no approved drugs or other therapeutics for the treatment of multidrug-resistant cancers, in recent years, studies have investigated the repurposing of tyrosine kinase inhibitors (TKIs) to act as agents against MDR mediated by ABCB1 and/or ABCG2. SKLB610 is a multi-targeted TKI with potent activity against vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor 2 (FGFR2). In this study, we investigate the interaction of SKLB610 with ABCB1 and ABCG2. We discovered that neither ABCB1 nor ABCG2 confers resistance to SKLB610, but SKLB610 selectively sensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer agents in a concentration-dependent manner. Our data indicate that SKLB610 reverses ABCG2-mediated MDR by attenuating the drug-efflux function of ABCG2 without affecting its total cell expression. These findings are further supported by results of SKLB610-stimulated ABCG2 ATPase activity and in silico docking of SKLB610 in the drug-binding pocket of ABCG2. In summary, we reveal the potential of SKLB610 to overcome resistance to cytotoxic anticancer drugs, which offers an additional treatment option for patients with multidrug-resistant cancers and warrants further investigation.
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Antineoplásicos , Neoplasias , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportadoras de Casetes de Unión a ATP , Adenosina Trifosfato/farmacología , Antineoplásicos/farmacología , Benzamidas , Línea Celular Tumoral , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Proteínas de Neoplasias/metabolismo , Ácidos Picolínicos , Inhibidores de Proteínas Quinasas/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Ensartinib (X-396) is a promising second-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK) that was developed for the treatment of ALK-positive non-small-cell lung cancer. Preclinical and clinical trial results for ensartinib showed superior efficacy and a favorable safety profile compared to the first-generation ALK inhibitors that have been approved by the U.S. Food and Drug Administration. Although the potential mechanisms of acquired resistance to ensartinib have not been reported, the inevitable emergence of resistance to ensartinib may limit its therapeutic application in cancer. In this work, we investigated the interaction of ensartinib with P-glycoprotein (P-gp) and ABCG2, two ATP-binding cassette (ABC) multidrug efflux transporters that are commonly associated with the development of multidrug resistance in cancer cells. Our results revealed that P-gp overexpression, but not expression of ABCG2, was associated with reduced cancer cell susceptibility to ensartinib. P-gp directly decreased the intracellular accumulation of ensartinib, and consequently reduced apoptosis and cytotoxicity induced by this drug. The cytotoxicity of ensartinib could be significantly reversed by treatment with the P-gp inhibitor tariquidar. In conclusion, we report that ensartinib is a substrate of P-gp, and provide evidence that this transporter plays a role in the development of ensartinib resistance. Further investigation is needed.
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BACKGROUND: Feticide was suggested to avoid delivering children with abnormalities. Recently, twin pregnancies have increased. Selective feticide was proposed to achieve a good outcome of pregnancy. This study aimed to evaluate the performance of feticide in twin pregnancy with fetal anomaly. METHODS: This was a retrospective study enrolled from 2009 to 2018. A total of 68 pregnancies with fetal anomalies received feticide. Potassium chloride was injected into the left ventricle to induce fetal asystole. Maternal and fetal characteristics of 16 dichorionic twins were documented to compare before and after 24th gestational week. RESULTS: All pregnant women received feticide without any maternal or fetal complication. The reasons for choosing feticide were divided into four groups, including morphologic defect (61.8%), genetic-chromosomal abnormality (30.9%), obstetrical complication (5.9%), and maternal request (1.5%). Mean gestational age at delivery was significantly higher in dichorionic twins who underwent selective feticide before than after 24th gestational week (36.7 vs 33.4, p = 0.04). CONCLUSION: Intracardiac injection of potassium chloride was effective for feticide and safe for mothers and fetuses. Selective feticide served as an alternative approach for twin pregnancy with fetal anomaly after sufficient discussion.
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Aborto Inducido , Anomalías Congénitas/epidemiología , Embarazo Gemelar , Adulto , Femenino , Edad Gestacional , Humanos , Embarazo , Embarazo Gemelar/genética , Estudios Retrospectivos , TaiwánRESUMEN
AIMS/INTRODUCTION: Women with excessive gestational weight gain (GWG) are at a higher risk for complications during pregnancy, such as preeclampsia. However, the association between excessive GWG and gestational diabetes mellitus (GDM) remains unclear. MATERIALS AND METHODS: We retrospectively reviewed 8,352 women from our obstetric database with singleton pregnancies who gave birth after 28 completed weeks of gestation between January 1, 2012, and December 31, 2016, excluding pregnancies complicated by fetal anomalies, fetal death, and overt diabetes. Diagnosis of GDM was based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups. We used two classification methods to define excessive GWG: a weight gain above the 90th percentile of the population, or exceeding the upper range recommended by the Institute of Medicine, stratified by pre-pregnancy body mass index. Statistical analysis was performed using multiple logistic regression to determine the association between excessive GWG and the risk of GDM. RESULTS: Overall, 1,129 women (13.5%) were diagnosed with GDM. There was no difference in GWG between women with and without GDM in the first trimester and before GDM screening. Women with GDM had significantly less GWG in the second trimester, after GDM screening, and throughout the whole gestation than women without GDM. No correlation was found between excessive GWG in the first and second trimesters, before GDM screening, and the later development of GDM. CONCLUSIONS: Our results indicate that excessive GWG prior to GDM screening is not associated with an increased risk of GDM.
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Diabetes Gestacional , Ganancia de Peso Gestacional , Índice de Masa Corporal , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Femenino , Humanos , Embarazo , Resultado del Embarazo , Segundo Trimestre del Embarazo , Estudios Retrospectivos , Aumento de PesoRESUMEN
Background: Dysregulation of placental mechanistic target of rapamycin (mTOR) activity has been implicated in the pathophysiology of pregnancies complicated by idiopathic fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) with large-for-gestational-age (LGA) infants. However, the underlying mechanisms remain unclear. Methods: We obtained placentas from women with normal pregnancies (n = 11) and pregnancies complicated by FGR (n = 12) or GDM with LGA infants (n = 12) to compare the levels of total and phosphorylated forms of Akt, AMPK, TSC2, and mTOR among the three groups and used primary cytotrophoblast cells isolated from 30 normal term placentas to study the effects of oxygen-glucose deprivation (OGD) and increasing glucose concentrations on the changes of these factors in vitro. Results: Placentas from FGR pregnancies had lower phosphorylated Akt (p-Akt) levels (P < 0.05), higher p-AMPKα levels (P < 0.01), and lower mTOR phosphorylation (P < 0.05) compared to that of normal pregnant women. Conversely, women with GDM and LGA infants had higher p-Akt (P < 0.001), lower p-AMPKα (P < 0.05), and higher p-mTOR levels (P < 0.05) in the placentas than normal pregnant women. Furthermore, primary cytotrophoblast cells subjected to OGD had lower p-Akt and p-mTOR (both P < 0.05) and higher p-AMPKα levels (P < 0.05) than those cultured under standard conditions, but increasing glucose concentrations had opposite effects on the respective levels. Administering compound C, an AMPK inhibitor, did not significantly affect Akt phosphorylation but partially reversed mTOR phosphorylation. Administering LY294002, an Akt inhibitor, decreased p-mTOR levels, but did not change the levels of total and phosphorylated AMPKα. Conclusion: These results suggest that Akt and AMPK are involved in the regulation of trophoblast mTOR activity in the placentas of pregnancies complicated by FGR and GDM with LGA infants.
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Background: Despite reports of the beneficial effects, such as increasing hemoglobin level and iron store in the neonatal period, of delayed cord clamping, or umbilical cord milking after delivery in healthy term-born infants, the duration of delayed clamping or rounds of milking in most previous reports were determined arbitrarily and varied widely across different studies. Methods: We prospectively recruited 80 women with normal singleton pregnancies at 38-40 weeks' gestation. Participants were classified according to the mode of delivery and randomly assigned to either collecting blood from the placenta by umbilical cord drainage (CD) or cord milking (CM), with the placenta left in the uterus. The volume of blood collected, the duration of CD, and the number of rounds of CM were recorded. Results: Collected placental residual blood volume positively correlated with birth weight, placental weight, and length of the cord. When 80% of the total placental residual blood volume collected was set as the threshold, more than 80% of women who delivered vaginally reached this level within 60 s of CD or seven repetitions of CM. This amount of blood could be obtained within 120 s of CD or after seven repetitions of CM in more than 80% of women who underwent cesarean delivery. Conclusion: In most women, regardless of birth weight and placental weight, more than 80% of placental residual blood volume could be collected by CD within 60 s after vaginal delivery, 120 s after cesarean delivery, and seven repetitions of CM in both vaginal and cesarean deliveries.
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OBJECTIVE: We present a case of choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain. CASE REPORT: The patient is a 34-year-old multiparous woman with her second pregnancy, and a history of scoliosis with spinal fixation. Her first pregnancy was uneventful, with a term vaginal delivery. She was hospitalized four times due to intractable back pain from 25 to 31 weeks, and terminated at 31 weeks. The placenta was unremarkable on gross examination. Postpartum, the patient developed obstructive ileus, requiring a rectosigmoid resection. She was diagnosed with metastatic choriocarcinoma to the liver, para-aortic lymph nodes, and mesentery. A week later, she developed micro-thrombosis of all limbs, massive ascites, pleural effusion. Patient refused chemotherapy and died on post-operative Day 15. CONCLUSION: Presentation of choriocarcinoma in pregnancy varies widely. Clinicians should consider the differential diagnosis of choriocarcinoma when faced with abnormal unexplained symptoms during pregnancy.