Репозиторий Университета

© 2020 Elsevier B.V. Introduction: Vaginal birth after caesarean delivery is associated with better outcomes compared to repeat caesarean section. Accurate antenatal risk stratification of women undergoing a trial of labor after caesarean section is crucial in order to maximize perinatal and maternal outcomes. The primary aim of this study was to explore the role of antepartum ultrasound in predicting the probability of vaginal birth in women attempting trial of labor; the secondary aim was to build a multiparametric prediction model including pregnancy and ultrasound characteristics able to predict vaginal birth and compare its diagnostic performance with previously developed models based exclusively upon clinical and pregnancy characteristics. Methods: Prospective study of consecutive singleton pregnancies scheduled for trial of labor undergoing a dedicated antepartum ultrasound assessment at 36–38 weeks of gestation. Head circumference, estimated fetal weight cervical length, sub-pubic angle were recorded before the onset of labour. The obstetricians and midwives attending the delivery suite were blinded to the ultrasound findings. Multivariate logistic regression and area under the curve analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting vaginal birth. Comparison with previously reported clinical models developed by the Maternal-Fetal Medicine Unit Network (Grobman's models) was performed using De Long analysis. Results: A total of 161women who underwent trial of labor were included in the study. Among them 114 (70.8 %) women had successful vaginal birth. At multivariable logistic regression analysis maternal height (adjusted odds ratio (aOR):1.24;9 5% Confidence Interval (CI)1.17−1.33), previous C-section for arrest labor (aOR:0.77; 95 %CI0.66−0.93), cervical dilation at admission (aOR:1.35; 95 %CI1.12−1.74), fetal head circumference (aOR:0.77; 5%CI0.43−0.89), subpubic angle (aOR:1.39 95 %CI1.11−1.99) and cervical length (aOR:0.82 95 % CI0.54−0.98) were independently associated with VBAC. A model integrating these variables had an area under curve of 0.839(95 % CI 0.710−0.727) for the prediction of vaginal birth, significantly higher than those achieved with intake (0.694; 95 %CI0.549−0.815; p = 0.01) and admission (0.732: 95 % CI 0.590−0.84; p = 0.04) models reported by Grobman. Conclusion: Antepartum prediction of vaginal birth after a caesarean section is feasible. Fetal head circumference, subpubic angle and cervical length are independently associated and predictive of vaginal birth. Adding these variables to a multiparametric model including maternal parameters improves the diagnostic accuracy of vaginal birth compared to those based only on maternal characteristic.

© 2020 Elsevier B.V. Introduction: Vaginal birth after caesarean delivery is associated with better outcomes compared to repeat caesarean section. Accurate antenatal risk stratification of women undergoing a trial of labor after caesarean section is crucial in order to maximize perinatal and maternal outcomes. The primary aim of this study was to explore the role of antepartum ultrasound in predicting the probability of vaginal birth in women attempting trial of labor; the secondary aim was to build a multiparametric prediction model including pregnancy and ultrasound characteristics able to predict vaginal birth and compare its diagnostic performance with previously developed models based exclusively upon clinical and pregnancy characteristics. Methods: Prospective study of consecutive singleton pregnancies scheduled for trial of labor undergoing a dedicated antepartum ultrasound assessment at 36–38 weeks of gestation. Head circumference, estimated fetal weight cervical length, sub-pubic angle were recorded before the onset of labour. The obstetricians and midwives attending the delivery suite were blinded to the ultrasound findings. Multivariate logistic regression and area under the curve analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting vaginal birth. Comparison with previously reported clinical models developed by the Maternal-Fetal Medicine Unit Network (Grobman's models) was performed using De Long analysis. Results: A total of 161women who underwent trial of labor were included in the study. Among them 114 (70.8 %) women had successful vaginal birth. At multivariable logistic regression analysis maternal height (adjusted odds ratio (aOR):1.24;9 5% Confidence Interval (CI)1.17−1.33), previous C-section for arrest labor (aOR:0.77; 95 %CI0.66−0.93), cervical dilation at admission (aOR:1.35; 95 %CI1.12−1.74), fetal head circumference (aOR:0.77; 5%CI0.43−0.89), subpubic angle (aOR:1.39 95 %CI1.11−1.99) and cervical length (aOR:0.82 95 % CI0.54−0.98) were independently associated with VBAC. A model integrating these variables had an area under curve of 0.839(95 % CI 0.710−0.727) for the prediction of vaginal birth, significantly higher than those achieved with intake (0.694; 95 %CI0.549−0.815; p = 0.01) and admission (0.732: 95 % CI 0.590−0.84; p = 0.04) models reported by Grobman. Conclusion: Antepartum prediction of vaginal birth after a caesarean section is feasible. Fetal head circumference, subpubic angle and cervical length are independently associated and predictive of vaginal birth. Adding these variables to a multiparametric model including maternal parameters improves the diagnostic accuracy of vaginal birth compared to those based only on maternal characteristic.

© 2019 Elsevier B.V. Objective: Early pregnancy models for prediction of GDM have been proposed, mostly using anamnestic and biochemical parameters. The aim of our study was to evaluate the strength of association of first trimester fetal heart rate (FHR) in predicting the development of gestational diabetes (GDM). Study design: We considered in our analysis singleton non-diabetic pregnant women who underwent a first trimester screening at 11–14 weeks. Data on maternal age, BMI, cigarette smoking, NT, FHR, CRL, DV-PVI, β-hCG and PAPP-A were included in the analysis. Multivariate logistic regression analysis was used to estimate the association between maternal characteristics and first-trimester ultrasound measurements and GDM. We evaluated the efficacy of different models for the prediction of GDM. Results: We considered 603 women, of whom 199 (33%) were subsequently diagnosed with GDM. ROC analysis showed that first trimester FHR was highly predictive of GDM (AUC 0.809, 95% CI 0.769–0.849, p < 0.001). At FPR of 20%, first trimester FHR had a detection rate of 65.2% for GDM (positive likelihood ratio: 3.26; negative likelihood ratio: 0.43), which increased to 89.5% at FPR of 40% (positive likelihood ratio: 2.24; negative likelihood ratio: 0.17). When considering as threshold 162 bpm, FHR showed detection rate of 76.9%, specificity of 67.1% and negative predictive value of 85.5% for GDM. Conclusion: This is the first study to highlight the potential role of first trimester FHR as early predictor of GDM. In our cohort, a threshold of 162 bpm has shown high detection rate and NPV for GDM.

© 2019 Elsevier Masson SAS The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections. The ability of the medicinal leech Hirudo medicinalis to store blood for months with little change has attracted interest regarding the identification of novel AMPs in this organism. In this study, we employed computational algorithms to the medicinal leech genome assembly to identify amino acid sequences encoding potential AMPs. Then, we synthesized twelve candidate AMPs identified by the algorithms, determined their secondary structures, measured minimal inhibitory concentrations against three bacterial species (Escherichia coli, Bacillus subtilis, and Chlamydia thrachomatis), and assayed cytotoxic and haemolytic activities. Eight of twelve candidate AMPs possessed antimicrobial activity, and only two of them, 3967 (FRIMRILRVLKL) and 536–1 (RWRLVCFLCRRKKV), exhibited inhibition of growth of all tested bacterial species at a minimal inhibitory concentration of 10 μmol. Thus, we evidence the utility of the developed computational algorithms for the identification of AMPs with low toxicity and haemolytic activity in the medicinal leech genome assembly.

© 2018, MDPI AG. All rights reserved. Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come.

© 2018 Wiley-VCH Verlag GmbH  &  Co. KGaA, Weinheim Phosphorolytic transglycosylation catalyzed by nucleoside phosphorylases is an important biotechnological process. The reaction is reversible, and the yield of the target nucleoside depends on its concentration at the equilibrium state. We have shown that initial concentrations of the starting compounds and the phosphorolysis equilibrium constants of starting and final glycosides determine concentrations of all the components at the equilibrium state. Based on that, we developed a novel quantitative approach for the prediction of yields in transglycosylation reactions. This method simplifies the choice of reagent concentrations and their ratios for the maximization of the target nucleoside yield. It is advantageous over widely applied blind and cumbersome trial-and-error approach and can reduce the required chemical and energy resources. The described algorithm could also be applied for other equilibrium transfer reactions. (Figure presented.).

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text