Effects of first and second trimester vaginal bleeding on pregnancy outcome

The effects of vaginal bleeding during first and second trimester on pregnancy outcomes was assessed in a hospital-based population of 268 non-diabetic women. The group of non-bleeders comprised 173 females whereas, there were 71 females with first and 24 with second trimester bleeding. Fetal loss (abortion) occurred in 34% of first trimester and 25% of second trimester bleeders. Low birth weight and preterm delivery were significantly associated with second trimester haemorrhage. The results suggest that first and second trimester vaginal bleeding correlates with adverse infant outcomes

Non-mean-field Vicsek-type models for collective behavior

We consider interacting particle dynamics with Vicsek-type interactions, and their macroscopic Partial Differential Equation (PDE) limit, in the non-mean-field regime; that is, we consider the case in which each particle/agent in the system interacts only with a prescribed subset of the particles in the system (for example, those within a certain distance). In this non-mean-field regime the influence between agents (i.e. the interaction term) can be normalized either by the total number of agents in the system (global scaling) or by the number of agents with which the particle is effectively interacting (local scaling). We compare the behavior of the globally scaled and the locally scaled systems in many respects, considering for each scaling both the PDE and the corresponding particle model. In particular, we observe that both the locally and globally scaled particle system exhibit pattern formation (i.e. formation of traveling-wave-like solutions) within certain parameter regimes, and generally display similar dynamics. The same is not true of the corresponding PDE models. Indeed, while both PDE models have multiple stationary states, for the globally scaled PDE such (space-homogeneous) equilibria are unstable for certain parameter regimes, with the instability leading to traveling wave solutions, while they are always stable for the locally scaled one, which never produces traveling waves. This observation is based on a careful numerical study of the model, supported by further analysis

Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Intel·ligència artificial; Eltrombopag; Trombocitopènia immune primàriaInteligencia artificial; Eltrombopag; Trombocitopenia inmune primariaArtificial intelligence; Eltrombopag; Primary immune thrombocytopeniaEltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP.This research was funded and promoted by Novartis, which contributed to setting up fundamental questions relevant for the study and reviewing the manuscript. However, the company did not have a role on study design, data collection, analysis, or interpretation

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Evaluación del ISTH-BAT en los trastornos plaquetarios congénitos: correlación clínica, laboratorio y molecular

CO-153 Introducción: Los trastornos plaquetarios congénitos (TPC) son un grupo heterogéneo de enfermedades raras, que se clasifican en trombocitopenias hereditarias (THs) y en trombocitopatías hereditarias (TFPs). Su identificación inicial y su diagnóstico final son complejos. Éste, se basa en la la historia clínica, la exploración física, pruebas de laboratorio fenotípicas y la confirmación de la alteración molecular subyacente. Por otra parte, la valoración de la clínica hemorrágica suele ser subjetiva, por lo que la Sociedad Internacional de Trombosis y Hemostasia (ISTH) recomienda la utilización de escalas de sangrado (bleeding assessment tools, BAT). Los objetivos de nuestros estudios fueron a) evaluar la clínica hemorrágica con el ISTH-BAT en pacientes diagnosticados de TPC, b) su comparación entre THs y TFPs y c) su relación con las pruebas funcionales y moleculares. Métodos: Estudio retrospectivo de 138 pacientes con TPC incluidos en el proyecto nacional “Caracterización funcional y molecular de los TPC” de la SETH. La clínica hemorrágica se evaluó mediante el ISTHBAT, obteniendo un score de sangrado (BS). El diagnóstico fenotípico se realizó mediante hemograma y frotis de sangre periférica, la función plaquetaria mediante agregometría de transmisión de luz (LTA) y citometría de flujo (CMF) y el diagnóstico molecular mediante secuenciación ..

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 </=16, 16-24, and >24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention