COVID-19 during pregnancy, delivery and postpartum period based on EBM

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the reason of theglobal health crisis. Since the first case of diagnosed COVID-19 pneumonia was reported in Wuhan, Hubei Province, China,in December 2019, the infection has spread rapidly to all over the world.The knowledge gained from previous human coronavirus infection outbreaks suggests that pregnant women and theirfoetuses represent a high-risk population during infectious disease epidemics.Moreover, a pregnancy, due to the physiological changes involving immune and cardiopulmonary systems, is a statepredisposing women to respiratory complications of viral infection.The constantly increasing number of publications regarding the course of COVID-19 infection in pregnant women has beenpublished, however, the available data remains limited and many questions remain unanswered. The aim of this reviewwas to summarize the literature data and adjusted to current recommendations regarding pregnancy care, delivery andpostpartum period.An extremely important issue is the need to register all the cases of COVID-19 affected women and the course of thesepregnancies to local, regional, or international registries, which will be helpful to answer many clinical and scientific questionsand to create guidelines ensuring an adequate level of care for women affected by COVID-19 infection during pregnancy,delivery and during postpartum period, as well as their newborns

Diketopiperazine-Based, Flexible Tadalafil Analogues: Synthesis, Crystal Structures and Biological Activity Profile

Phosphodiesterase 5 (PDE5) is one of the most extensively studied phosphodiesterases that is highly specific for cyclic-GMP hydrolysis. PDE5 became a target for drug development based on its efficacy for treatment of erectile dysfunction. In the present study, we synthesized four novel analogues of the phosphodiesterase type 5 (PDE5) inhibitor—tadalafil, which differs in (i) ligand flexibility (rigid structure of tadalafil vs. conformational flexibility of newly synthesized compounds), (ii) stereochemistry associated with applied amino acid building blocks, and (iii) substitution with bromine atom in the piperonyl moiety. For both the intermediate and final compounds as well as for the parent molecule, we have established the crystal structures and performed a detailed analysis of their structural features. The initial screening of the cytotoxic effect on 16 different human cancer and non-cancer derived cell lines revealed that in most cases, the parent compound exhibited a stronger cytotoxic effect than new derivatives, except for two cell lines: HEK 293T (derived from a normal embryonic kidney, that expresses a mutant version of SV40 large T antigen) and MCF7 (breast adenocarcinoma). Two independent studies on the inhibition of PDE5 activity, based on both pure enzyme assay and modulation of the release of nitric oxide from platelets under the influence of tadalafil and its analogues revealed that, unlike a reference compound that showed strong PDE5 inhibitory activity, the newly obtained compounds did not have a noticeable effect on PDE5 activity in the range of concentrations tested. Finally, we performed an investigation of the toxicological effect of synthesized compounds on Caenorhabditis elegans in the highest applied concentration of 6a,b and 7a,b (160 μM) and did not find any effect that would suggest disturbance to the life cycle of Caenorhabditis elegans. The lack of toxicity observed in Caenorhabditis elegans and enhanced, strengthened selectivity and activity toward the MCF7 cell line made 7a,b good leading structures for further structure activity optimization and makes 7a,b a reasonable starting point for the search of new, selective cytotoxic agents

Hyperglycemia in pregnancy — prevalence and perinatal outcomes. A retrospective multicenter cohort study in Poland

Objectives: Hyperglycemia in pregnancy (HIP) is one of the most common complications of pregnancy. Recently adopted new criteria for the diagnosis of HIP as well as the greater prevalence of risk factors could have a significant impact on HIP prevalence. The objective of the study was to assess the rates of HIP and the associated complications. Material and methods: This was a retrospective analysis of clinical records from pregnant women who delivered in eight tertiary hospitals in Poland in 2016. Results: The number of pregnant women with hyperglycemia totaled 1280 (7.25%), including gestational diabetes mellitus (GDM) in 1169 (6.62%) women and pregestational diabetes mellitus (PGDM) in 111 (0.63%). In addition to dietary modifications, 477 (41% of the GDM group) women received medical treatment (GDMG2). In women with PGDM multiple daily insulin injections (MDI) were used in 53 (47.7%) cases, continuous subcutaneous insulin infusions (CSII) in 57 (51.3%) cases and one woman was treated with metformin. The rate of cesarean sections was 69.4% and 62.9% for PGDM and GDM, respectively. Large-for-gestational-age (LGA) infants accounted for 38% and 21% of births in the PGDM and GDM groups, respectively. Of note are high rates of hyperbilirubinemia in infants born to mothers treated with insulin (13.5% for PGDM and 14.4% for GDMG2) vs infants born to mothers with diet (GDMG1) (3.4%). Conclusions: In Poland, the prevalence of HIP has nearly doubled in the past twenty years. Even with appropriate management, HIP is a significant risk factor for a cesarean section delivery, bearing an LGA infant and adverse neonatal outcomes