La insuficiencia venosa crónica en el periodo gestacional

La enfermedad venosa crónica es una condición persistente, progresiva y frecuentemente subestimada; ampliamente representada en la población general, que tiene un enorme impacto socioeconómico, físico y psicológico asociado. Las mujeres tienen un mayor riesgo de aparición de insuficiencia venosa debido a diferentes factores hormonales y fisiológicos, especialmente durante el período gestacional. El objetivo de la tesis es evaluar el impacto de la insuficiencia venosa crónica en mueres durante la gestación. Para ello, se han realizado diferentes trabajos, presentándose esta tesis por compendio de artículos. El artículo I es una revisión bibliográfica actualizada de la Enfermedad Venosa Crónica, incluyendo su epidemiología, etiología y factores de riesgo, la fisiopatología y semiología de estos pacientes, incluidas las manifestaciones clínicas, el diagnóstico y los tratamientos¿encontrándose que prácticamente no existen estudios del efecto de la aparición de enfermedad venosa en las mujeres durante la gestación. El artículo II, es un estudio transversal en el que se analiza y demuestra la asociación entre la aparición de varices infradiafragmáticas durante la gestación y alteraciones fetoplacentarias observadas por los clínicos y reflejadas en sus informes de alta, secundarias a hipoxia por compromiso fetal intraparto. El artículo III es un estudio longitudinal en el que se hace analiza si existe alteración en la estructura y función celular de la placenta que sea el sustrato de los resultados gestacionales. En concreto, la implicación de la ILK y un conjunto de cadherinas (e-adherina, cadherina-6, y cadherina 7) en la placenta de mujeres con enfermedad venosa.Aims: Chronic venous disease is a persistent, progressive and frequently underestimated condition, despite being widely represented in the general population in the World. It has been demonstrated that women has a higher risk of suffer venous insufficiency problems due to the different hormonal and physiological factors they present during the perinatal period. The general objective of this dissertation is to evaluate the specific impact of venous insufficiency in perinatal women. Methods: To achieve the objective stated above, we conducted 3 specific scientific studies. In the study I，we carried out a cross-sectional descriptive bibliographic review of all the research published on chronic venous disease since 1988. From this review, we compiled the most relevant evidence published on the topic of chronic venous disease, with special emphasis on the pathophysiology and medical cognition of disease. Secondly, the article II includes a cross-sectional study, in which we use accurate and updated data from the administrative medical records (CMBD) corresponding to the care registered in 2015, both in the public and private health systems of the different Autonomous Communities of Spain. We used these data to study the association between the prevalence of LEPVI and different risk factors, such as smoking, obesity, asthma, hypothyroidism, and intrapartum fetal distress. We performed a conditional logistic regression to estimate the adjusted odds ratios and the 95% Confidence Intervalto assess the associations between LEPVI and the risk factors, as well as their relationship with intrapartum fetal distress. Finally, in Article III we developed an observational, analytical and prospective study which included a sample of 114 women in the third trimester of pregnancy. A cohort study was conducted by gathering information from a database from the Carlos III Health Institute in 2017. Of these, 62 women were diagnosed with CVD according to the CEAP classification. The rest of women (n= 52) did not presented CVD diseases in their Electronic Health Record, and were included in the control group. Those women IX with CVD during pregnancy were identified to investigate its relationship with ILK expression in placental villi associated with E-cadherin. The relationship between the expression level of Cadherin 17 and Cadherin 6 with CVD was also explored. For this purpose, we conducted a conditional logistic regression model to obtain 95% confidence intervals (95% CI) during pregnancy. Results：Each study included in this dissertation provided several results which jointly contributed to achieving the objective of this thesis. In article I, we find that CVD is a progressive and disabling condition widely represented in the world population. We compiled some of the most relevant data on such a complex topic, with special emphasis on the pathophysiological and medical perceptions of the disease. In particular for the most vulnerable groups, such as the elderly people, individuals with additional comorbidities and pregnant women. In article II, we observed that, women with LEPVI were older and presented higher prevalence of smoking, obesity, asthma, and hypothyroidism, in comparision with those without LEPVI in the group control. In addition, women with LEPVI were more likely to have conditions associated with intrapartum fetal distress (9.35%) than women without this disease (7.41%). Women with LEPVI are 30% (OR = 1.30, 99.5% CI: 1.08-1.54) more likely to have an IFC outcome during the pregnancy, and to have placental dysfunction (OR = 1.74, 99.5% CI: 1.00-3-05), as well. After adjusting for age, smoking, obesity, asthma, hypothyroidism, coagulopathy disorders, and anemia, this association remained significant but slightly attenuated for IFC (OR=1.25, 99.5% CI, 1.05-1 .50) and placental dysfunction (OR = 1.23, 99.5% CI: 1.01-1.49). However, there was no association between LEPVI and fetal distress (OR = 1.01, 99.5% CI: 0.46- 2.21). In article III, women with CVeD during pregnancy show an increase in ILK expression in the placental villi associated with a decrease in E-cadherin. Histological analysis of protein expression by immunohistochemical techniques showed a significant increase X in ILK expression in placental villi of women with CVD during pregnancy compared to HC, ***p < 0.001 [CVeD = 2.379 ± 0.084 vs HC = 0.976 ± 0.082]. In contrast, we observed a significant decrease in E-Cad gene expression in the placental villi of women with CVeD during pregnancy compared to HC, **p = 0.0084 [CVeD = 10.726 ± 0.359 vs HC = 11.893 ± 0.461]. In addition, protein expression showed a significant decrease in E-Cad expression in the placental villi of women with CVeD during pregnancy compared to HC, ***p = 0.002 [CVeD = 0.903 ± 0.062 vs HC = 1.240 ± 0.058]. The expression level of Cadherin 17 and Cadherin 6 increases in the placental villi of women with CVD during pregnancy. Cad-17 gene expression showed a significant increase in placental villi of women with CVD during pregnancy compared to HC, *p = 0.0228 [CVeD = 7.804 ± 0.325 vs HC = 6.780 ± 0.263]. In this sense, protein expression showed a significant elevation by immunohistochemical techniques in the placental villi of women with CVD during pregnancy compared to HC, ** p = 0.0026 [CVeD = 1.403 ± 0.067 vs HC = 1.159 ± 0.085 ]. Similarly, our results have shown an increase in Cad-6 gene expression in the placental villi of women with CVD during pregnancy compared to HC, ** p = 0.0016 [CVeD = 7.083 ± 0.251 vs HC = 5.807 ± 0.247]. Furthermore, protein expression showed a significant increase in the placental villi of women with CVeD during pregnancy compared to HC, **p = 0.0033 [CVeD = 1.202 ± 0.065 vs HC = 0.923 ± 0.066]. Conclusions: CVD is a progressive and disabling disease with high impact in the world population health. Therefore, the management of pathophysiology and therapeutics is fundamental and was one of the objectives of our study. An increasing number of studies, focused on CVD, show the relevance of this vascular pathology, especially in the most advanced stages (CVI). In this dissertation, we collect some of the most relevant data on this important topic, with a special emphasis on pathophysiological and medical insights into the disease. An integrative perspective of this condition would bring immediate benefits for the clinical management of these patients, particularly for the most vulnerable groups, such as the elderly people, individuals with additional comorbidities and pregnant women. XI The second study aimed to determine the association between varicose veins in pregnancy and placental insufficiency. This study represented a nationwide crosssectional analysis in Spain to explore the association between the presence of varicose veins and the existence of alterations in the ischemic placental function. An extensive database gathered from hospital administrations was used for that purpose. In the third study, the relationship between chronic venous disease in pregnant women was observed, causing an increase in ILK in the placental villi associated with a decrease in E-Cadherin, demonstrating a significant increase in the expression of ILK proteins and genes, cadherin-6 and cadherin-17 and a reduction in e-cadherin, associated with the development of CVD during pregnancy

rDNA internal transcribed spacer sequence analysis of Lycoris Hert.

The interspecific relationships of Lycoris species were studied by internal transcribed spacer (ITS) sequences. ITS fragments of 14 species were amplified, sequenced and analysed. The results showed that ITS sequences of 14 species were different from each other and the ITS lengths of 14 species were about 652 bp. The GC content of ITS2 sequences was bigger than that of ITS1. Clustering results based on ITS sequences showed that Lycoris species could be divided into three clades. The classification was basically consistent with those of karyotype and morphology. This paper suggested that the likelihood of hybrid origin of Lycoris species was supported and ITS could be used as a good molecular marker to identify plants of Lycoris.Keywords: Lycoris Hert., internal transcribed spacer (ITS), molecular taxonomy, interspecific relationshipAfrican Journal of Biotechnology Vol. 11(29), pp. 7361-7365, 10 April, 201

MiR-550a-3p restores damaged vascular smooth muscle cells by inhibiting thrombomodulin in an <em>in vitro</em> atherosclerosis model

Thrombomodulin (TM) is involved in the pathological process of atherosclerosis; however, the underlying mechanism remains unclear. Oxidised low-density lipoprotein (Ox-LDL; 100 μg/mL) was used to induce human vascular smooth muscle cells (HVSMCs) into a stable atherosclerotic cell model. The expression levels of miR-550a-3p and TM were detected by real-time reverse transcription-polymerase chain reaction. Cell proliferation was estimated using CCK8 and EDU assays. Wound scratch and transwell assays were used to measure the ability of cells to invade and migrate. Propidium iodide fluorescence-activated cell sorting was used to detect apoptosis and cell cycle changes. A dual-luciferase reporter assay was performed to determine the binding of miR-550a-3p to TM. Our results suggested the successful development of a cellular atherosclerosis model. Our data revealed that TM overexpression significantly promoted the proliferation, invasion, migration, and apoptosis of HVSMCs as well as cell cycle changes. Upregulation of miR-550a-3p inhibited the growth and metastasis of HVSMCs. Furthermore, miR-550a-3p was confirmed to be a direct target of TM. Restoration of miR-550a-3p expression rescued the effects of TM overexpression. Thus, miR-550a-3p might play a role in atherosclerosis and, for the first time, normalised the function of injured vascular endothelial cells by simultaneous transfection of TM and miR-550a-3p. These results suggest that the miR-550a-3p/TM axis is a potential therapeutic target for atherosclerosis

Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Existence and Ulam Type Stability for Impulsive Fractional Differential Systems with Pure Delay

Through literature retrieval and classification, it can be found that for the fractional delay impulse differential system, the existence and uniqueness of the solution and UHR stability of the fractional delay impulse differential system are rarely studied by using the polynomial function of the fractional delay impulse matrix. In this paper, we firstly introduce a new concept of impulsive delayed Mittag–Leffler type solution vector function, which helps us to construct a representation of an exact solution for the linear impulsive fractional differential delay equations (IFDDEs). Secondly, by using Banach’s and Schauder’s fixed point theorems, we derive some sufficient conditions to guarantee the existence and uniqueness of solutions of nonlinear IFDDEs. Finally, we obtain the Ulam–Hyers stability (UHs) and Ulam–Hyers–Rassias stability (UHRs) for a class of nonlinear IFDDEs

Estimation and Inference in Heterogeneous Spatial Panels with a Multifactor Error Structure

We develop a unifying econometric framework for the analysis of heterogeneous panel data models that can account for both spatial dependence and common factors. To tackle the challenging issues of endogeneity due to the spatial lagged term and the correlation between the regressors and factors, we propose the CCEX-IV estimation procedure that approximates factors by the cross-section averages of regressors and deals with the spatial endogeneity using the internal instrumental variables. We develop the individual and Mean Group estimators, and establish their consistency and asymptotic normality. By contrast, the Pooled estimator is shown to be inconsistent in the presence of parameter heterogeneity. Monte Carlo simulations confirm that the finite sample performance of the proposed estimators is quite satisfactory. We demonstrate the usefulness of our approach with an application to the house price growth for Local Authority Districts in the UK over 1997Q1-2016Q4

Research on Dynamic Integrity Measurement Model Based on Memory Paging Mechanism

In order to solve the existed problems of dynamic integrity measurement method, a dynamic integrity measurement model based on Memory Paging Mechanism is proposed in this paper. The model takes memory pages of executable subjects as measurement objects. When the pages are scheduled into memory, the measurement points are inserted, the pages are measured, and their integrities are verified. The model is able to insure the integrity and trust of each executable page and assure that the integrity of the whole executable subjects is not destroyed. To verify this model, XEN hypercall mechanism is used to acquire executable subjects’ pages scheduled into memory, and the integrity measurement and verification codes are put into hypercall handler. Accordingly, dynamic integrity measurement to executable subjects is implemented

MiR-638 repressed vascular smooth muscle cell glycolysis by targeting LDHA

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) accelerated vascular diseases progression, like atherosclerosis and restenosis. MicroRNAs were reported to participate in modulating diverse cellular processes. Here, we focused on exploring the role of miR-638 in VSMCs glycolysis and underlying mechanism