El derecho al desistimiento del consumidor en el ámbito contractual

El presente trabajo pretende analizar de forma general el contenido del derecho de desistimiento, principalmente entre el derecho de desistimiento legal y el derecho de desistimiento contractual, y cómo afectan estos a los consumidores y usuarios. Teniendo también en cuenta precisamente, aquellas excepciones a este. Y lo que considero más importante, exponer los diferentes plazos que nos pueden ofrecer, dependiendo del tipo de producto o servicio, e incluso siendo el mismo producto o servicio, los diferentes plazos que nos ofrece una empresa u otra -a pesar del plazo general que establece el Texto Refundido de la Ley General de Consumidores y Usuarios-.The present work intends to analyze in a general way the content of the law of withdrawal, mainly between the legal law of withdrawal and the contractual law of withdrawal, and how these fail consumers and users. Also taking into account precisely those exceptions to this. And what I consider most important, expose the different terms that can offer us, depending on the tipo of producto or service, and even being the same product or service, the different therms that one company or another offers us- despise the general termn that establishes the “Texto Refundido de la ley General de Consumidores y Usuarios”

hemostatic changes in pregnancy

Normal pregnancy is associated with changes in all aspects of haemostasis, including increase in concentrations of most clotting factors, decreasing concentrations of some of the natural anticoagulants and diminishing fibrinolytic activity. These changes help in maintaining placental function during pregnancy but result in a state of hypercoagulability that may predispose to thrombosis and placental vascular complications. During pregnancy, the concentrations of coagulation factors V, VII, VIII, IX, X, XII and von Willebrand factor rise significantly, accompanied by a pronounced increase in fibrinogen levels which increases up to two-fold from non-pregnant levels. Furthermore, there is a decrease in physiological anticoagulants manifested by a significant reduction in protein S activity and by acquired activated protein C resistance. The overall fibrinolytic activity is impaired during pregnancy, but returns rapidly to normal following delivery. This is largely due to placental derived plasminogen activator inhibitor type 2 (PAI-2), which is present in substantial quantities during pregnancy. D-Dimer levels increase in pregnancy but are not thought to indicate intravascular coagulation as fibrinolysis is depressed. These D-Dimers may originate from the uterus. Finally, the platelet count decreases in normal pregnancy possibly due to increased destruction and haemodilution with a maximal decrease in the third trimester. Immediately after delivery there is an increase in platelet count, especially in patients undergoing cesarean section. During treatment of severe post-partum hemorrhage, it is absolutely essential to have the knowledge that the starting values of the platelets are very different as compared to a non-pregnant patient. Moreover, after delivery, also the levels of fibrinogen increase. Since the value of fibrinogen represents a crucial parameter for the management of acute bleeding, it is essential to administer the proper amount of fibrinogen in the case of postpartum hemorrhage. This aspect is emphasized especially in relation to the use of thromboelastography and for a correct interpretation of the results. Thromboelastogram profiles strongly depend on the amount of platelets and fibrinogen in whole blood. Protocols for thromboelastogram guided administration of hemocomponents and coagulation factor concentrates in cases of acute bleeding in pregnancy and post-partum are required

Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance

Abstract Background Microparticles (MPs) are vesicular structures shed from endothelial or circulating blood cells, after activation or apoptosis, and can be considered markers of vascular damage. We aimed to determine the levels of circulating MPs, their content of miRNA-126-3p and 5p, and their relationship with early endothelial activation/damage, in patients with different degree of glucose tolerance. Methods CD62E+, CD62P+, CD142+, CD45+ circulating MPs, their apoptotic (AnnexinV+) fractions, and miRNA-126 expression were determined in 39 prediabetic (PreDM), 68 type 2 diabetic (T2DM), and 53 control (NGT) subjects, along with main anthropometric and biochemical measurements. MPs were analysed by flow cytometry. miRNA-126 was measured by quantitative real-time PCR. Plasma antioxidant capacity was determined by electronic spin resonance; ICAM-1, and VCAM-1 by ELISA. Results Activated endothelial cell-derived MPs (CD62E+) were significantly increased in PreDM and T2DM in comparison to NGT (p < 0.0001). AnnexinV+/CD62E+ MPs and Annexin V+ MPs were significantly increased in T2DM compared to PreDM and NGT (p < 0.001); other MPs were not significantly different among groups. Plasma antioxidant capacity was significantly decreased in PreDM and T2DM compared to NGT (p = 0.001); VCAM-1 significantly increased in PreDM and T2DM in comparison to NGT (p = 0.001). miR-126-3p expression, but not miR-126-5p, in MPs, decreased significantly and progressively from NGT, to PreDM, and T2DM (p < 0.001). In PreDM and T2DM, CD62E+ MPs level was significantly and negatively associated with plasma glucose (p = 0.004). Conclusion We show for the first time that circulating CD62E+ MPs level and miR-126-3p content in MPs are abnormal in subjects with pre-diabetes; the content of miR-126-3p correlates with markers of endothelial inflammation, such as VCAM-1, plasma antioxidant capacity, and microparticles, well-accepted markers of endothelial dysfunction

Cryptogenic ischemic stroke in cardiac transthyretin amyloidosis and sinus rhythm: a case report

Cardiac amyloidosis is a group of diseases characterized by the deposition of amyloid fibers in cardiac tissue. Two forms are mainly reported: light chain (AL) and transthyretin (ATTR) amyloidosis. Among the complications of transthyretin amyloidosis there are thrombotic events and, to a lesser extent, hemorrhagic events. The latter are likely caused by perivascular amyloid deposition resulting in capillary fragility, in addition to INR lability during anticoagulant therapy. The onset of thrombotic events may be caused by the high prevalence of atrial fibrillation (AF), mechanical cardiac dysfunction and atrial myopathy observed in patients with transthyretin amyloidosis. It remains unclear why thromboembolic events occur even in patients with sinus rhythm or adequate anticoagulation, though a hypercoagulable state or underlying inflammation may be involved. We report a case of cryptogenic ischemic stroke in an 86-year-old woman with transthyretin amyloidosis and sinus rhythm. Traditional coagulation tests, whole blood rotational thromboelastometry and impedance aggregometry did not show a hypercoagulable state. The thrombin generation assay did not reveal a prothrombotic state. However, the study of extracellular vesicles highlighted underlying immune-mediated endothelial damage likely responsible for the thrombotic diathesis. It could be hypothesized that inflammation plays a role in the hypercoagulability of patients with transthyretin amyloidosis. Larger prospective studies are needed to validate our hypothesis

Association between non-O blood type and early unexplained recurrent spontaneous abortion in women with and without inherited thrombophilia

We retrospectively evaluated the prevalence of non-O blood type – the most frequently inherited prothrombotic factor – and inherited thrombophilia (IT) in a group of women with recurrent spontaneous abortion (RSA). All consecutive women with a history of early unexplained RSA who underwent a screening for IT between December 2008 and December 2021 were considered for enrolment. A group of healthy, age-matched women with ≥1 normal pregnancy and no adverse pregnancy outcomes acted as controls. Two hundred and seventeen women were enrolled. The adjusted odds ratio (aOR) of RSA in non-O vs. O blood type was 1.37 (95% CI, 1.04-2.78), and in women with vs. without IT was 1.26 (95% CI, 1.08-3.61); aOR of RSA in women with non-O blood type and IT was 2.52 (95% CI, 1.12-5.47). We observed a significant association between non-O blood group or IT and RSA. The concomitant presence of non-O blood group and IT further increases RSA risk

Iron capture through CD71 drives perinatal and tumor-associated Treg expansion

: Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth

Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

Although the association between cancer and venous thromboembolism (VTE) has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway(1,2). Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis

Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation

Abstract: In haemostasis and thrombosis, platelet, coagulation and anticoagulation pathways act together to produce fibrin-containing thrombi. We developed a microspot-based technique, in which we assessed platelet adhesion, platelet activation, thrombus structure and fibrin clot formation in real time using flowing whole blood. Microspots were made from distinct platelet-adhesive surfaces in the absence or presence of tissue factor, thrombomodulin or activated protein C. Kinetics of platelet activation, thrombus structure and fibrin formation were assessed by fluorescence microscopy. This work revealed: (1) a priming role of platelet adhesion in thrombus contraction and subsequent fibrin formation; (2) a surface-independent role of tissue factor, independent of the shear rate; (3) a mechanism of tissue factor-enhanced activation of the intrinsic coagulation pathway; (4) a local, suppressive role of the anticoagulant thrombomodulin/protein C pathway under flow. Multiparameter analysis using blood samples from patients with (anti)coagulation disorders indicated characteristic defects in thrombus formation, in cases of factor V, XI or XII deficiency; and in contrast, thrombogenic effects in patients with factor V-Leiden. Taken together, this integrative phenotyping approach of platelet–fibrin thrombus formation has revealed interaction mechanisms of platelet-primed key haemostatic pathways with alterations in patients with (anti)coagulation defects. It can help as an important functional add-on whole-blood phenotyping

Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication

HIV-1 replication results in mitochondrial damage that is enhanced during antiretroviral therapy (ART). The onset of HIV-1 replication is regulated by viral protein Tat, a 101-residue protein codified by two exons that elongates viral transcripts. Although the first exon of Tat (aa 1–72) forms itself an active protein, the presence of the second exon (aa 73–101) results in a more competent transcriptional protein with additional functions. Results: Mitochondrial overall functions were analyzed in Jurkat cells stably expressing full-length Tat (Tat101) or one-exon Tat (Tat72). Representative results were confirmed in PBLs transiently expressing Tat101 and in HIV-infected Jurkat cells. The intracellular expression of Tat101 induced the deregulation of metabolism and cytoskeletal proteins which remodeled the function and distribution of mitochondria. Tat101 reduced the transcription of the mtDNA, resulting in low ATP production. The total amount of mitochondria increased likely to counteract their functional impairment. These effects were enhanced when Tat second exon was expressed. Conclusions: Intracellular Tat altered mtDNA transcription, mitochondrial content and distribution in CD4+ T cells. The importance of Tat second exon in non-transcriptional functions was confirmed. Tat101 may be responsible for mitochondrial dysfunctions found in HIV-1 infected patients.We greatly appreciate the secretarial assistance of Mrs Olga Palao. This work was supported by FIPSE (360924/10), Spanish Ministry of Economy and Competitiveness (SAF2010-18388), Spanish Ministry of Health (EC11- 285), AIDS Network ISCIII-RETIC (RD12/0017/0015), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness (FIS PI12/00506). The work of Sara Rodríguez-Mora is supported by a fellowship of Sara Borrell from Spanish Ministry of Economy and Competitiveness (2013). The work of María Rosa López-Huertas is supported by a fellowship of the European Union Programme Health 2009 (CHAARM).S