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1.
Am J Obstet Gynecol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38527604

RESUMO

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

2.
Prenat Diagn ; 43(7): 919-928, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36575575

RESUMO

OBJECTIVE: Skeletal dysplasia is usually apparent in the second trimester. First trimester femur-length/biparietal diameter (FL/BPD), FL/abdominal circumference (AC) and FL/foot for the screening of skeletal dysplasia were evalauted. METHOD: Case-control study: pregnancies with molecular confirmation of skeletal dysplasia undergoing nuchal translucency (January_2007-December_2021). Controls included pregnancies without fetal abnormalities. Performance of FL/BPD, FL/AC and FL/foot was evaluated by receiver operating characteristic curves. RESULTS: Twenty-eight skeletal dysplasia cases were identified; 17 (60.71%) corresponded to lethal types. Compared to 184 controls, cases had a lower median FL/BPD (0.34 [IQR 0.30-0.38] vs. 0.44 [IQR 0.39-0.48]; p < 0.001), FL/AC (0.13 [IQR 0.09-0.15] vs. 0.15 [IQR 0.13-0.16]; p = 0.001) and FL/foot (0.84 [IQR 0.76-0.91] vs. 1.01 [IQR 0.94-1.11]; p < 0.001). FL/BPD and FL/foot ratios had a superior area under the curve (0.846 and 0.853, respectively) than FL/AC (0.64). The probability of diagnosing skeletal dysplasia increased at least 9-fold if FL/BPD <0.376 (OR 26.05, 95% CI 9.79-69.3; p < 0.001) and 14-fold if FL/foot <0.891 (OR 39.46, 95% CI 14.17-109.9; p < 0.001). Low FL/BPD and FL/foot were associated significantly with lethal types compared to viable skeletal dysplasia. CONCLUSIONS: First trimester FL/BPD and FL/foot may be of clinical utility in the detection of skeletal dysplasia especially when there is another suspicious sonographic sign or when there is a relevant family history before overt second trimester sonographic markers become apparent.


Assuntos
Fêmur , Ultrassonografia Pré-Natal , Gravidez , Feminino , Humanos , Primeiro Trimestre da Gravidez , Estudos de Casos e Controles , Fêmur/diagnóstico por imagem , Biometria , Idade Gestacional
3.
BMC Pregnancy Childbirth ; 23(1): 553, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532986

RESUMO

BACKGROUND: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. METHODS: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. RESULTS: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. CONCLUSIONS: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , COVID-19/diagnóstico , Morte Fetal , Parto , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Estudos Retrospectivos , SARS-CoV-2 , Resultado da Gravidez
4.
Cell Physiol Biochem ; 54(3): 457-473, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32369692

RESUMO

BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells. METHODS: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern. RESULTS: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells. CONCLUSION: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Imunossupressores/farmacologia , Neoplasias Hepáticas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Tacrolimo/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Everolimo/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Interferente Pequeno , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Proteína 1A de Ligação a Tacrolimo/metabolismo , Proteína Supressora de Tumor p53/metabolismo , eIF-2 Quinase/metabolismo
5.
Prenat Diagn ; 40(7): 813-824, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32274806

RESUMO

OBJECTIVE: To establish whether fetal cerebral vasoreactivity (CVRO2 ), following maternal hyperoxia, is predicted by fetal cerebral and uteroplacental Doppler pulsatility indices (PI) at baseline, fetal pulmonary vasoreactivity to oxygen (PVRO2 ), gestational age (GA), or sex. METHODS: Pulsatility index of middle (MCA), anterior (ACA), posterior cerebral (PCA), umbilical (UA), uterine (UtA), and branch of the pulmonary arteries (PA) were obtained, by ultrasound, before (baseline), during (hyperoxia) and after 15 minutes of maternal administration of 8 L/min of 100% oxygen, through a non-rebreathing face mask, in normal singleton pregnancies within 20 to 38 weeks' gestation. CVRO2 was defined as changes greater than zero in z score of PI of the cerebral arteries from baseline to hyperoxia. Logistic modeling was applied to identify CVRO2 predictors. RESULTS: A total of 97 pregnancies were eligible. In the overall population, median z scores of PI of MCA, ACA, and PCA did not differ between study phases. Based on the logistic model, baseline z scores for cerebral PI and GA were the best predictors of CVRO2 . CONCLUSIONS: In low-risk pregnancies, fetal CVRO2 to hyperoxia does not occur uniformly but depends on cerebral PI and GA at baseline. These findings may provide useful reference points when oxygen is administered in high-risk pregnancies.


Assuntos
Transtornos Cerebrovasculares/etiologia , Doenças Fetais/etiologia , Hiperóxia/complicações , Doença Aguda , Adulto , Velocidade do Fluxo Sanguíneo , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiopatologia , Transtornos Cerebrovasculares/congênito , Transtornos Cerebrovasculares/fisiopatologia , Estudos Transversais , Feminino , Feto/irrigação sanguínea , Idade Gestacional , Humanos , Hiperóxia/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Fluxo Pulsátil , Ultrassonografia Pré-Natal , Vasodilatação/fisiologia , Adulto Jovem
8.
Fam Pract ; 36(6): 693-698, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31044230

RESUMO

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.


Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Qualidade de Vida , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Atenção Primária à Saúde , Autocuidado/estatística & dados numéricos , Espanha , Inquéritos e Questionários
9.
J Cell Physiol ; 234(1): 692-708, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-30132846

RESUMO

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5'AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3-12 hr) ER stress characterized by an increase of Ser51 P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185 P-JNK1/2/JNK1/2, Thr172 P-AMPKα, Ser413 P-Foxo3a, Thr308 P-AKt/AKt and Thr32 P-Foxo3a/Foxo3a ratios, and reduction of Ser2481 P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL , Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308 P-AKt/AKt and Ser473 P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL , which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.


Assuntos
Estresse do Retículo Endoplasmático/genética , Neoplasias Hepáticas/tratamento farmacológico , Proteínas de Neoplasias/genética , Sorafenibe/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Biomarcadores Tumorais/genética , Caspase 3/genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição CHOP/genética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Perinat Med ; 46(2): 155-161, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28753545

RESUMO

OBJECTIVE: To investigate the role of adjuvant 17-α-hydroxy-progesterone caproate (17OHP-C) in reducing the risk of preterm delivery <34 weeks and adverse perinatal outcomes in women with ≥3 second trimester pregnancy losses attributed to cervical insufficiency undergoing prophylactic cerclage. MATERIAL AND METHODS: Retrospective cohort study of women with prophylactic cerclage placed between 2006 and 2014 divided into a cohort of (i) those receiving adjuvant 17OHP-C (n=43), and (ii) controls with cerclage alone (n=59). RESULTS: Demographic characteristics were comparable in both groups. There was no significant difference in gestational age at delivery between the cerclage-17OHP-C group (33.4±5.6 weeks) and the cerclage-alone group (34.4±4.6 weeks); P=0.33. We noted a non-significant increase for deliveries <34 weeks in the cerclage-17OHP-C group (44.2%) compared to controls (28.8%) which remained non-significant after adjusting for confounders; P=0.46. There was no statistically significant difference in the rate of delivery <37, 32, 28 and 24 weeks. Adverse neonatal outcomes were comparable in both groups (cerclage-17OHP-C 48.8% vs. cerclage-alone 39%); P=0.43. CONCLUSION: Intramuscular 17OHP-C in combination with prophylactic cerclage in women with cervical insufficiency and ≥3 second trimester pregnancy losses had no synergistic effect in reducing the rate of recurrent preterm birth or improving perinatal outcomes.


Assuntos
Cerclagem Cervical/métodos , Hidroxiprogesteronas/administração & dosagem , Nascimento Prematuro , Incompetência do Colo do Útero/terapia , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Estudos de Coortes , Antagonistas de Estrogênios/administração & dosagem , Feminino , Humanos , Injeções Intramusculares , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez/efeitos dos fármacos , Segundo Trimestre da Gravidez/fisiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Estados Unidos/epidemiologia , Incompetência do Colo do Útero/fisiopatologia
11.
Am J Obstet Gynecol ; 215(2): 235.e1-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26979631

RESUMO

BACKGROUND: Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery. OBJECTIVE: The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women. STUDY DESIGN: This is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term. RESULTS: Of the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term. CONCLUSION: We identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.


Assuntos
Negro ou Afro-Americano/genética , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Adulto , Alelos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-16/genética , Metaloproteinase 2 da Matriz/genética , Trabalho de Parto Prematuro/genética , Gravidez , Proteína Quinase C-alfa/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Adulto Jovem
12.
Hepatology ; 59(6): 2358-70, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24415412

RESUMO

UNLABELLED: The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4 -induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. CONCLUSIONS: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process.


Assuntos
Regulação para Baixo , Fator de Transcrição GATA4/fisiologia , Cirrose Hepática/metabolismo , Fígado/embriologia , Animais , Intoxicação por Tetracloreto de Carbono/complicações , Linhagem Celular , Matriz Extracelular/metabolismo , Células Estreladas do Fígado/fisiologia , Humanos , Integrases , Cirrose Hepática/etiologia , Mesoderma/metabolismo , Camundongos , Camundongos Transgênicos , Fenótipo
13.
Pediatr Infect Dis J ; 42(9): 781-786, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37260248

RESUMO

BACKGROUND: Pregnant patients with coronavirus disease 2019 (COVID-19) are at risk for adverse pregnancy outcomes. Although clinical outcomes for pregnant adults have been reported, the impact of COVID-19 on adolescents is lacking. We sought to evaluate obstetric outcomes of pregnant adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and compare them with uninfected adolescent controls. METHODS: Retrospective cohort study of pregnant adolescents (14-19 years) who had a positive polymerase chain reaction test for SARS-CoV-2 from April 2020 to December 2020 at Inova Health System Hospitals. Controls included pregnant adolescents who tested negative. The primary outcome was a composite of preeclampsia, preterm delivery, cesarean delivery, fetal growth restriction and stillbirth. Secondary outcomes included maternal and neonatal morbidity. RESULTS: Forty-eight pregnant adolescents who tested positive for SARS-CoV-2 were compared with 394 controls. Infected adolescents were more likely to be Hispanic (91.67% vs. 12.18%; risk ratio [RR] 41.85 [95% CI: 15.43-113.5]) and uninsured (50% vs. 7.87%; RR 7.04 [95% CI: 4.31-11.49]. Nearly 80% of infected adolescents remained asymptomatic, whereas one-third of symptomatic adolescents progressed to severe or critical COVID-19. The primary composite outcome was more prevalent in infected adolescents compared with noninfected controls (41.67% vs. 25.38%; adjusted RR 2.65 [95% CI: 1.19-5.93]). Maternal morbidity was more prevalent in infected adolescents (6.25% vs. 0.76%; adjusted RR 9.53 [95% CI: 3.83-23.71]). Primary and secondary maternal outcomes were more prevalent in younger adolescents and those with higher severity of COVID-19. Maternal SARS-CoV-2 infection was not associated with neonatal morbidity. CONCLUSIONS: Pregnant adolescents infected with SARS-CoV-2 are more likely to have adverse obstetric outcomes and maternal morbidity compared with noninfected pregnant adolescents.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Adulto , Humanos , Adolescente , SARS-CoV-2 , COVID-19/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Retrospectivos , Resultado da Gravidez , Nascimento Prematuro/epidemiologia
14.
Front Surg ; 10: 1048451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808255

RESUMO

Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it. Material and method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated "in situ" for transplantation, and those discarded after the "in situ" evaluation were considered as no transplantable liver grafts, while those grafts transplanted after "in situ" evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed. Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound (p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85. Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation.

15.
J Neurosurg Sci ; 67(4): 462-470, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34114432

RESUMO

BACKGROUND: The objective of this study is to compare percutaneous techniques (MIS) with the open technique in terms of angle correction, long-term maintenance and clinical results. METHODS: The authors collected a prospective database of thoraco-lumbar fractures treated with posterior stabilization without fusion from 2013 to 2019. The statistical analysis has been carried out retrospectively. The patients were classified into Open and MIS group. To compare the two population, samples, treatments and mitigate the differences between the groups, the propensity score (PS) matching was used. RESULTS: One hundred and eight patients with thoraco-lumbar fractures were included. After performing the PS, 21 patients were obtained in the open group and 28 in the MIS group. For operative and perioperative parameters there were no differences in number of patients with posterior decompression, number of instrumented segments, number of total screws, operative time and complications. Postoperative hemoglobin was similar in both groups. However, in the open group a greater loss of hemoglobin was observed; as well as, higher analgesia requirements and length of stay. No statistically significant differences were observed in neurological status in both groups in the preoperative, postoperative period and at follow-up. The Cobb angle showed no differences at admission comparing both groups. A similar angle correction was observed with both surgeries, but in open surgery there was a statistically significant loss of correction. CONCLUSIONS: We observed in this study that the MIS technique for the treatment of thoracolumbar fractures is as effective as the open technique in terms of angle correction; and demonstrated that is better in its maintenance over time. Clinical results were at least as good as with the open technique.


Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Fusão Vertebral , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Tempo , Vértebras Lombares/cirurgia , Vértebras Torácicas/cirurgia , Fusão Vertebral/métodos , Fixação Interna de Fraturas/métodos
16.
Am J Obstet Gynecol ; 207(6): 484.e1-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23108067

RESUMO

OBJECTIVE: The purpose of this study was to determine whether fetuin-A affects trophoblast viability and invasion, whether growth factors that bind receptors that activate tyrosine kinase are impaired by fetuin-A, and whether elevated maternal serum fetuin-A levels are associated with adverse pregnancy outcomes. STUDY DESIGN: We studied viability and invasion in first-trimester extravillous trophoblast cells that were exposed to fetuin-A, insulin-like growth factor, and placental growth factor. Insulin receptor substrates expression was assessed. We compared serum fetuin-A levels in 111 preeclampsia cases and 95 controls. RESULTS: Fetuin-A reduced extravillous trophoblast cell viability and invasion in the presence or absence of growth factors. Fetuin-A reduced insulin receptor substrate-1 and tyrosine phosphorylated insulin receptor substrate-1 expression in extravillous trophoblast cells that had been treated with insulin-like growth factor. Elevated serum fetuin-A levels were more prevalent in preeclampsia cases than control subjects, even after we controlled for diabetes mellitus, hypertension, and obesity. CONCLUSION: Fetuin-A may decrease trophoblast viability and invasion caused by the inhibition of receptor tyrosine kinase activity. Elevated serum levels of fetuin-A may be associated with preeclampsia.


Assuntos
Resultado da Gravidez , Trofoblastos/efeitos dos fármacos , alfa-2-Glicoproteína-HS/farmacologia , Adulto , Western Blotting , Estudos de Casos e Controles , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Placentário , Pré-Eclâmpsia/sangue , Gravidez , Proteínas da Gravidez/farmacologia , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/metabolismo , Trofoblastos/enzimologia , Trofoblastos/fisiologia , Adulto Jovem , alfa-2-Glicoproteína-HS/metabolismo
17.
Rev Biol Trop ; 60(1): 369-79, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22458231

RESUMO

Most studies on Eugerres mexicanus mainly consider biogeographic and systematic aspects and rarely address reproductive characteristics, which are useful for fishery population management plans. This study aimed at evaluating the ontogeny of E. mexicanus, based on 30 embryos and 30 larvae sampled by induced spawning of breeders, taken in February 2009 from the Usumacinta River in Tenosique, Tabasco, Mexico. All descriptions of the embryonic development were based on morphometric and meristic data and followed standard methods. Eggs, recovered at the gastrula stage, had an average diameter of 1.17mm (SD=0.08). The bud stage appeared during the first three hours of development, in which the posterior side was adhered to the vitellus; Kupffer's vesicle was visible. Yolk-sac larvae hatched 18 hours after fertilization, exhibiting a light brown color and an average total length of 2.94mm (SD=0.70); the preflexion stage was reached eight days after hatching, with a total average length of 4.67mm (SD=0.50) and a total notochord length of 4.45mm (SD=0.50). The flexion stage was reached on the 16th day, with an average total length of 6.66mm (SD=1.53), while postflexion was reached on the 24th day, with 10.33mm (SD=1.45). The pre-juvenile stage was reached on the 33rd day, with a total length of 14.30mm (SD=0.93), showing IX spines and 10 rays and III spines and eight rays in the dorsal and anal fins, respectively. The juvenile stage was reached by the 45th day, with an average length of 28.16mm (SD=1.93) and average weight of 4.75g (SD=1.49). Prejuveniles showed an initial pigmentation with dark colored dots in the superior and inferior jaw and dispersed on the head, while juveniles presented the same pigmentation pattern, decreasing towards the margin of the caudal peduncle. In conclusion, the embryonic developmental stages of E. mexicanus were typical for the Gerreidae group. However, their morphometric characters were slightly different since the diameter and size of the drop of oil were bigger than those reported for marine species. In addition, regarding pigmentation, the yolk-sac larvae of E. mexicanus were olive and yellow on the margin of the notochord, which differs from those reported for other species. This is the first recorded report on the reproductive biology and early life development of this species.


Assuntos
Embrião não Mamífero/embriologia , Perciformes/embriologia , Animais , Desenvolvimento Embrionário/fisiologia , Feminino , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Masculino , México
18.
J Matern Fetal Neonatal Med ; 35(25): 5970-5977, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33771091

RESUMO

OBJECTIVE: Pregnant women with moderate symptoms of COVID-19 are at risk for progressing to severe or critical illness. While there are limited data on the management of severe COVID-19 during pregnancy, information on pharmacological treatments of moderate COVID-19 is lacking. We report clinical outcomes of pregnant women hospitalized due to moderate COVID-19 illness treated with a 5-day course of remdesivir, antibiotics, and/or glucocorticoids. MATERIALS AND METHODS: Case series of pregnant women hospitalized with moderate symptoms of COVID -19 pneumonia at two INOVA Health System hospitals from April 1 to December 31, 2020. Primary outcome was clinical recovery (breathing on ambient air and/or hospital discharge) on hospital day 7 (HD7). Cox regression analysis was performed to evaluate which variables were associated with the primary outcome. RESULTS: Out of 748 pregnant women with confirmed infection by reverse transcriptase polymerase chain reaction, 35 were hospitalized due to moderate symptoms of COVID-19 pneumonia (median gestational age 29 weeks). There was no maternal death. Seventeen patients received remdesivir within 48 hours of hospitalization: 15 remained with moderate symptoms and 2 (who also received glucocorticoids) had progressed to critical COVID-19 at remdesivir initiation; all 17 women in this group achieved clinical recovery on HD7. Seven women received remdesivir >48 hours following admission after they began treatment with glucocorticoids ± antibiotics and worsened to severe or critical disease; they all required supplemental oxygen on HD7. Eleven women were treated with antibiotics ± glucocorticoids but no remdesivir; on HD7, 3/11 achieved clinical recovery. Clinical recovery was significantly different among treatment groups; p < 0.001. When analyzing only women who remained with moderate symptoms at pharmacological treatments initiation, all 15 on remdesivir and only 3 of 11 on antibiotics achieved clinical recovery on HD7; p < 0.001. Delaying remdesivir for >48 hours after admission (HR 2.32, 95% CI 1.45-4.16) and >4-day duration of symptoms prior to hospitalization (HR 1.65, 95% CI 1.27-3.50) had an inverse association with clinical recovery. Incidental oligohydramnios was seen in 3/24 (12.5%) of women within 5 days of completing remdesivir treatment. Elevated transaminases was prevalent in women treated with remdesivir (8/24, 33.3%). CONCLUSION: In our cohort, prompt initiation of remdesivir in pregnant women hospitalized with moderate symptoms of COVID-19 pneumonia within 48 hours of admission prevented worsening and allowed a fast clinical recovery by HD7. Deferring remdesivir for >48 hours after hospitalization and duration of symptoms >4 days before admission were independently associated with delayed clinical recovery and longer hospital admission. Ultrasound evaluation of the amniotic fluid in patients recovering from COVID-19 hospitalization should be considered.


Assuntos
Tratamento Farmacológico da COVID-19 , Feminino , Humanos , Gravidez , Lactente , SARS-CoV-2 , Gestantes , Hospitalização , Antibacterianos/uso terapêutico
19.
Minerva Surg ; 77(4): 327-334, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34338467

RESUMO

BACKGROUND: The aim of this study is to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure. METHODS: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. NOM, based on intravenous antibiotics (ATB) and bowel rest, was defined as unsuccessful when emergency surgery (ES) and/or infection-related death took place. Patients initially treated with ES were excluded. Analysis was done with the IBM SPSS statistics 23.0.0.2 software. RESULTS: According to modified Hinchey and WSES criteria, 99 (12%) of 826 AD episodes were complicated, with pneumoperitoneum on the CT scan in 89 (90.5%). NOM was undertaken in 93 (94%) cases, with a 91.5% success rate. Multivariate analysis revealed ASA class III-IV, and the presence of fluid collections >3 cm in diameter, but not distant free air, to be associated with NOM failure. However, the success rate of NOM was significantly higher in patients with pericolic pneumoperitoneum (98.5%) than in those with distant free air (80%) (P=0.02). Risk factors of NOM failure were an advanced age, high CRP and WBC values, and the presence of free fluid in >2 abdominal quadrants. CONCLUSIONS: NOM in hemodynamically stable patients with complicated AD is a safe and feasible approach, even in the context of distant free air. Nevertheless, patients with isolated pericolic air did better in our series.


Assuntos
Diverticulite , Pneumoperitônio , Diverticulite/terapia , Humanos , Pneumoperitônio/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
20.
Am J Hypertens ; 35(4): 311-318, 2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-34525175

RESUMO

BACKGROUND: We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. METHODS: This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. RESULTS: Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. CONCLUSION: PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.


Assuntos
Adiponectina , Síndrome Metabólica , Adulto , Biomarcadores , Estudos Transversais , Humanos , Metaloproteinase 2 da Matriz , Inibidor 1 de Ativador de Plasminogênio
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