2D-dwell-time analysis with simulations of ion-channel gating using high-performance computing.

Single-channel patch-clamp recordings allow observing the action of a single protein complex in real time and hence the deduction of the underlying conformational changes in the ion-channel protein. Commonly, recordings are modeled using hidden Markov chains, connecting open and closed states in the experimental data with protein conformations. The rates between states denote transition probabilities that could be modified by membrane voltage or ligand binding. Modeling algorithms have to deal with limited recording bandwidth and a very noisy background. It was previously shown that the fit of two-dimensional (2D)-dwell-time histograms with simulations is very robust in that regard. Errors introduced by the low-pass filter or noise cancel out to a certain degree when comparing experimental and simulated data. In addition, the topology of models (that is, the chain of open and closed states) could be inferred from 2D-histograms. However, the 2D-fit was never applied to its full potential. A major reason may be the extremely time-consuming and often unreliable fitting process, due to the stochastic variability in the simulations. We have now solved these issues by introducing a message-passing interface (MPI) allowing massive parallel computing on a high-performance computing (HPC) cluster and obtaining ensemble solutions. With ensembles, we have demonstrated how important ranked solutions are for difficult tasks related to a noisy background, fast gating events beyond the corner frequency of the low-pass filter, and topology estimation of the underlying Markov model. Finally, we have shown that, by combining the objective function of the 2D-fit with the deviation of the current amplitude distributions, automatic determination of the current level of the conducting state is possible, even with an apparent current reduction due to low-pass filtering. Making use of an HPC cluster, the power of 2D-dwell-time analysis can be used to its fullest with minor input of the experimenter.

The Impact of Periodontal Disease on Preterm Birth and Preeclampsia.

This review delves into the possible connection between periodontitis and negative pregnancy outcomes, such as preeclampsia and preterm birth. It highlights the potential influence of an unidentified microbial factor on preeclampsia and the effects of inflammatory responses on the rate of preterm births. Furthermore, it underscores the prevalent occurrence of oral ailments within the populace and their significant repercussions on quality of life. Hormonal fluctuations during pregnancy may exacerbate oral conditions such as pregnancy gingivitis and periodontitis, necessitating bespoke therapeutic approaches that take into account potential fetal ramifications. Periodontal disease, characterized by microbial attack and inflammatory response, results in tissue destruction and tooth loss. The oral cavity's susceptibility to bacterial colonization, which is primarily due to its role as a site for food intake, is highlighted. Furthermore, research indicates a correlation between inflammatory responses and factors such as prostaglandin E2 and IL-1ß, and preterm birth. Therapeutic interventions are a focus of international research, with efforts being aimed at optimizing outcomes through larger studies involving pregnant women.

A Systematic Review about Cervical Pregnancy and our Experience.

Background: Cervical ectopic pregnancy is a relatively rare type of ectopic pregnancy and has no standardized guidelines for management. Methods: This systematic review is based on the collection of case reports, published in PubMed/MEDLINE about the resolution of ectopic cervical pregnancies over the last decade and the presentation of a case managed in our healthcare unit. Studies involving cervical pregnancy in the first trimester with the presence of a viable embryo and ß-hCG in the serum below 100.000 mIU/mL were included, while heterotopic pregnancies were excluded. Results: Nineteen articles reporting twenty-three case reports are demonstrated explicitly emphasizing on the management techniques. There is no established approach for the management of this type of ectopic pregnancy. Conclusion: It is important to consider the conservative approaches as first-line treatment in all cases of cervical pregnancy preserving fertility. Minimally invasive methods are also described and preferred as second-line treatment, as reported in our literature review.

Association of Anti-Ro/SSA and Anti-La/SSB Autoantibodies With Pregnancy Outcome in the General Population.

Background: Autoimmune diseases encompass a diverse array of disorders that disturb the optimal functioning of the immune system, which is to eliminate the 'foreign or/and dangerous' to mistakenly target the body's own tissues. Objective: The aim of this research is to evaluate the most effective approach to managing autoimmune diseases within the framework of pregnancy. Methods: The exact causes and etiologies of these diseases are multifactorial and mostly still unclear. Ro/SSA autoantibodies and La/SSB, could be found in Sjögren's disease (SJ), systemic lupus (SLE) and other autoimmune disorders. Smoking, stress, UV exposure, vitamin D deficiency, and other genetic and environmental factors have been identified as risk factors for rheumatic diseases. Results: Over the years, an ever-increasing incidence of these diseases has been observed in the general population, with the female sex being at increased risk for their occurrence. This fact raises the question of what should be the management of these pathological entities during pregnancy. Taking into account the very significant impact on the quality of paitients'daily life and the seemingly augmented prevalence of autoimmune diseases, as well as their preference in the female population, the reasonable question arises as to what should be the optimal management of these diseases in the context of pregnancy. Conclusion: Given the limited data of the global medical community regarding the etiological factors and mechanisms that trigger the onset of rheumatic diseases, the management of pregnant women is a complex conundrum that health professionals are challenged to face and solve.

The Impact of Adenomyosis on Pregnancy.

Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis.

Safety of COVID-19 Vaccination in Pregnancy: A Systematic Review.

The COVID-19 pandemic has posed significant risks to pregnant women and those recently pregnant, leading to heightened mortality and morbidity rates. Vaccination has emerged as a pivotal strategy in reducing COVID-19-related deaths and illnesses worldwide. However, the initial exclusion of pregnant individuals from most clinical trials raised concerns about vaccine safety in this population, contributing to vaccine hesitancy. This review aims to consolidate the existing literature to assess the safety and efficacy of COVID-19 vaccination in pregnant populations and neonatal outcomes. Diverse studies were included evaluating various aspects of safety for women and their newborns, encompassing mild to severe symptoms across different vaccines. The findings indicate the overall safety and efficacy of COVID-19 vaccination, with minimal adverse outcomes observed, including mild side effects like pain and fever. Although most studies reported the absence of severe adverse outcomes, isolated case reports have raised concerns about potential associations between maternal COVID-19 vaccination and conditions such as fetal supraventricular tachycardia and immune-mediated diseases. Our review underscores the importance of ongoing surveillance and monitoring to ensure vaccine safety in pregnant women. Overall, COVID-19 vaccination during pregnancy remains a safe and effective strategy, emphasizing the need for continued research and vigilance to safeguard maternal and fetal health.

Our Experience with Hydrogel-Coated Trisacryl Microspheres in Uterine Artery Embolization for the Treatment of Symptomatic Uterine Fibroids and Adenomyosis: A Follow-Up of 11 Years.

Uterine artery embolization (UAE) for the treatment of symptomatic uterine fibroids and non-controllable adenomyosis symptoms is a relatively new procedure for organ-preserving therapy. These benign conditions can become symptomatic in about 30% of women between the ages of 35 and 50. The purpose of the UAE either for fibroids or adenomyosis is the elimination of blood loss, the reduction in pain, and bulky or rectal pressure symptoms. The purpose of this study is to present our experience in UAE with the use of hydrogel-coated tris acryl microspheres for the treatment of symptomatic uterine fibroids and adenomyosis.