No massive black holes in the Milky Way halo.

The gravitational wave detectors have unveiled a population of massive black holes that do not resemble those observed in the Milky Way1-3 and whose origin is debated4-6. According to one possible explanation, these black holes may have formed from density fluctuations in the early Universe (primordial black holes)7-9, and they should comprise from several to 100% of dark matter to explain the observed black hole merger rates10-12. If such black holes existed in the Milky Way dark matter halo, they would cause long-timescale gravitational microlensing events lasting years13. The previous experiments were not sufficiently sensitive to such events14-17. Here we present the results of the search for long-timescale microlensing events among the light curves of nearly 80 million stars located in the Large Magellanic Cloud that were monitored for 20 years by the OGLE survey18. We did not find any events with timescales longer than one year, whereas all shorter events detected may be explained by known stellar populations. We find that compact objects in the mass range from 1.8 × 10-4 to 6.3 M⊙ cannot compose more than 1% of dark matter, and those in the mass range from 1.3 × 10-5 to 860 M⊙ cannot make up more than 10% of dark matter. Thus, primordial black holes in this mass range cannot simultaneously explain a significant fraction of dark matter and gravitational wave events.

Intrahepatic Cholestasis of Pregnancy during COVID-19 Pandemic.

Background and Objectives: Intrahepatic cholestasis of pregnancy (ICP) stands as one of the most prevalent concerns in maternal-fetal medicine, presenting a significant risk to fetal health and often associated with liver dysfunction. Concurrently, the coronavirus-19 (COVID-19) infection can lead to hepatic cell injury through both direct and indirect pathways. Hypothetically, these two conditions may coincide, influencing each other. This study aimed to comparatively assess the incidence and severity of ICP before and during the COVID-19 pandemic. Methods: A retrospective cohort study was conducted, comparing the incidence and severity of ICP between January 2018 and February 2020 (pre-COVID-19 period) and March 2020 to March 2022 (COVID-19 period) across two hospitals, encompassing 7799 deliveries. The diagnosis of ICP was established using the ICD-10 code and defined as total bile acids (BA) levels ≥ 10 µmol/L. Statistical analysis included descriptive statistics, Chi-square and Mann-Whitney U tests, as well as multiple or logistic regression analysis. Results: A total of 226 cases of ICP were identified. The incidence of mild cholestasis (BA < 40 µmol/L) was lower during the pandemic compared to before (3% before versus 2%, p < 0.05), while the incidence of moderate and severe ICP remained unchanged (0.6% before vs. 0.4%, p = 0.2). Overall, the total incidence of ICP was lower during the pandemic (3.6% before versus 2.4%, p = 0.01). No significant differences were observed in severity (as defined by BA and liver function test levels), rates of caesarean section, or neonatal birth weights. Conclusions: During the COVID-19 pandemic, the total incidence of ICP appeared to be lower. However, this reduction was primarily observed in cases of mild ICP, potentially indicating challenges in detection or reduced access to medical services during this period. The incidence of moderate and severe ICP remained unchanged, suggesting that these forms of the condition were unaffected by the pandemic's circumstances.

From Brush to Dendritic Structure: Tool for Tunable Interfacial Compatibility between the Iron-Based Particles and Silicone Oil in Magnetorheological Fluids.

Comprehensive magnetic particle stability together with compatibility between them and liquid medium (silicone oil) is still a crucial issue in the case of magnetorheological (MR) suspensions to guarantee their overall stability and MR performance. Therefore, this study is aimed at improving the interfacial stability between the carbonyl iron (CI) particles and silicone oil. In this respect, the particles were modified with polymer brushes and dendritic structures of poly(2-(trimethylsilyloxy)ethyl methacrylate) (PHEMATMS), called CI-brushes or CI-dendrites, respectively, and their stability properties (corrosion, thermo-oxidation, and sedimentation) were compared to neat CI ones. Compatibility of the obtained particles and silicone oil was investigated using contact angle and off-state viscosity investigation. Finally, the magneto-responsive capabilities in terms of yield stress and reproducibility of the MR phenomenon were thoroughly investigated. It was found that MR suspensions based on CI-brushes had significantly improved compatibility properties than those of neat CI ones; however, the CI-dendrites-based suspension possessed the best capabilities, while the MR performance was negligibly suppressed.

COVID-19 Vaccination Status among Pregnant and Postpartum Women-A Cross-Sectional Study on More Than 1000 Individuals.

Pregnancy is a well-known factor for vaccine hesitancy and immunization remains the most effective form of prevention against coronavirus disease (COVID-19) related complications. The objective was to estimate vaccine uptake and hesitancy rate, characteristics, and factors contributing to a decision-making process among pregnant and postpartum individuals. This was a prospective cross-sectional study on 1033 pregnant (54.1%) and postpartum (45.9%) women conducted between December 2021 and March 2022 in a tertiary center for maternal−fetal medicine. Logistic regression was used to assess characteristics related to the vaccination decision process. Among responders, 74% were vaccinated and 26% were hesitant (9% planning to vaccinate and 17% totally opposed). Only 59.8% were offered a vaccine by healthcare professionals. Women with higher levels of education (OR 2.26, p < 0.0001), who received positive feedback about vaccination (OR 2.74, p = 0.0172), or were informed about COVID-19 complications in pregnancy (OR 2.6, p < 0.0001) were most likely to accept the vaccination. Hesitancy was associated with multiparity (≥3, OR 4.76, p = 0.006), worse educational status (OR 2.29, p < 0.0001), and lack of previous COVID-19 infection (OR 1.89, p < 0.0001). The most common reason for rejection was insufficient safety data (57%). Understanding factors behind vaccination status is crucial in lowering complications in mothers and newborns and targeted action may facilitate the uptake.

Comparative Genomic Hybridization to Microarrays in Fetuses with High-Risk Prenatal Indications: Polish Experience with 7400 Pregnancies.

The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.

Twin-to-twin transfusion syndrome complicated with in utero limb ischemia of the donor twin - a case report.

BACKGROUND: In utero limb ischemia is a rare complication of the monochorionic twin pregnancies complicated with twin to twin transfusion syndrome (TTTS). The condition is more often seen in recipient twins. There are few theories of the pathogenesis including in utero venous thromboembolism, but the cause remains unclear. However, limb ischemia is thought to be unrelated with any prenatal intervention. CASE PRESENTATION: We present a case of a monochorionic twin pregnancy complicated with TTTS admitted to the Clinic for selective fetoscopic laser photocoagulation. The invasive procedure failed due to poor visibility. In the following weeks of pregnancy, amnioreduction procedures were performed. At 28 weeks of gestation due to twin anemia-polycythemia sequence diagnosis the patient was qualified for cesarean section. Postnatally, the donor twin was diagnosed with lower right limb ischemic necrosis. The extremity was amputated 2 days later with an uncomplicated recovery. After speculations of the potential pathogeneses it was suggested that the ischemic limb occurred as a complication of the main condition - TTTS. CONCLUSIONS: In literature, there have been no cases reported of TTTS stage I complicated with donor twin limb ischemia. The actual cause of the in utero limb ischemic necrosis in monochorionic twins remains unknown. Nevertheless, increased attention to the potential complication after failed invasive procedures or conservative treatment should be required.

Prenatal Diagnosis by Array Comparative Genomic Hybridization in Fetuses with Cardiac Abnormalities.

Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.

Variability of the rs333 in Polish patients with lupus erythematosus.

INTRODUCTION: Lupus erythematosus (LE) is an autoimmune disease with a strong influence of genetic and environmental factors. C-C motif chemokine receptor 5 (CCR5) gene expression may affect the development and intensity of LE. AIM: To evaluate the possible association between the 32bp deletion in rs333 locus located within the CCR5 gene and the development of LE or the occurrence of various clinical symptoms in the course of the disease. MATERIAL AND METHODS: One hundred and twenty patients with LE (77 with systemic lupus erythematosus (SLE) and 43 with discoid lupus erythematosus (DLE)) and 100 healthy controls from the Polish population were genotyped for deletion in rs333. RESULTS: 32 bp deletion in the rs333 was significantly more frequent among healthy individuals than DLE patients. Moreover, heterozygotes and homozygotes with deletion in rs333 were significantly more frequent within the control group than the group of patients with discoid lupus erythematosus. In contrast, any statistically significant differences in allele or genotype frequencies between healthy persons and SLE patients were observed. Furthermore, nucleotide sequence variability of rs333 was not associated with certain clinical symptoms of LE patients. CONCLUSIONS: Deletion in the rs333 might be a protective factor for DLE, but not SLE in the Polish population. Nevertheless further studies performed on larger populations are needed to confirm these observations.

sFlt-1, Not PlGF, Is Related to Twin Gestation Choronicity in the First and Third Trimesters of Pregnancy.

BACKGROUND: Preeclampsia occurs more often in dichorionic than in monochorionic twin pregnancy. We hypothesize that serum concentrations of biomarkers: placental growth factor (PlGF), serum soluble fms-like tyrosine kinase-1 (sFlt-1), and endoglin (Eng) differ between monochorionic and dichorionic twin pregnancies. METHODS: A prospective observational study including 43 monochorionic and 36 dichorionic twin gestation was conducted. Blood samples were collected twice from all participants: between 11 + 0 and 13 + 6 and between 32 + 0 and 34 + 0 weeks of gestation. PlGF, sFlt-1 and Eng were measured using immnunoenzymatic assays. RESULTS: We found a significantly higher concentration of sFlt-1 in dichorionic in comparison to monochorionic pregnancies in both the first and third trimesters. PlGF and sEng levels did not differ between mono- and dichorionic gestation in both study periods. sFlt-1 level was related to twin gestation chorionicity, while PlGF expression was not. PlGF, sFlt-1 and sEng concentrations increased significantly during gestation and were much higher in the third trimester compared to the values measured in the first trimester. CONCLUSIONS: Angiogenic biomarkers expression differ between dichorionic and monochorionic twin pregnancy. The sFlt-1 level is related to chorionicity of a twin gestation.

COVID-19 Pandemic-Related Anxiety in Pregnant Women.

The COVID-19 pandemic outbreak influenced general and mental health worldwide. The objective of this study was to assess the anxiety level during the COVID-19 pandemic among pregnant women and compare it between COVID-infected and non-infected groups. We prospectively assessed the daily routine and anxiety level using a bespoke questionnaire and GAD-7 scale validated for pregnant women. With logistic regression, we established possible risk factors of generalized anxiety disorder spectrum and main causes of concern. The dataset included 439 responders of our survey. Of which, 21% had COVID-19 infection during pregnancy; 38% were screened for possible generalized anxiety disorder and the proportion was higher in women who suffered from COVID-19 (48% vs. 35%, p = 0.03). Pre-pregnancy anxiety or depression diagnosis and intentional social contact avoidance increased the risk of anxiety (aOR 3.4 and 3.2). Fetal wellbeing was the main concern for 66% of the responders. The COVID-19 pandemic and related restrictions substantially altered daily lives of pregnant women, exaggerating the prevalence of anxiety compared with the pre-COVID-19 studies (38% vs. 15%). COVID-19 infection during pregnancy was associated with increased levels of generalized anxiety scores. Patient-tailored psychological support should be a mainstay of comprehensive antenatal medical care in order to avoid anxiety- and stress-related complications.

Genetic Background of Fetal Growth Restriction.

Fetal growth restriction (FGR) is one of the most formidable challenges in present-day antenatal care. Pathological fetal growth is a well-known factor of not only in utero demise in the third trimester, but also postnatal morbidity and unfavorable developmental outcomes, including long-term sequalae such as metabolic diseases, diabetic mellitus or hypertension. In this review, the authors present the current state of knowledge about the genetic disturbances responsible for FGR diagnosis, divided into fetal, placental and maternal causes (including preeclampsia), as well as their impact on prenatal diagnostics, with particular attention on chromosomal microarray (CMA) and noninvasive prenatal testing technique (NIPT).

Both Low and High PAPP-A Concentrations in the First Trimester of Pregnancy Are Associated with Increased Risk of Delivery before 32 Weeks in Twin Gestation.

In twin gestation, the relationship between pregnancy associated plasma protein (PAPP-A) and perinatal outcome is unclear. The aim of the study was to determine if low and high concentrations of PAPP-A in the first trimester are related to perinatal outcome in twins. A retrospective study was conducted. Medical data of women in twin pregnancies who delivered between 2013 and 2018 were analyzed. PAPP-A concentrations were measured between 10 + 0 and 13 + 6 weeks. The associations between low (<10th percentile) and high (>90th percentile) values of PAPP-A and pregnancy complications were analyzed. A total of 304 patients were included. PAPP-A <10th percentile was associated with a high risk of preterm delivery (OR 6.14; 95% CI 2.1-18), delivery <34 weeks (OR 2.39; 95% CI 1.1-5.1) or <32 weeks (OR3.06; 95% CI 1.4-6.8). Significant relations between PAPP-A >90th percentile and delivery <34 weeks (OR4.09; 95% CI 1.8-9.1) or <32 weeks (OR 2.83; 95% CI 1.2-6.6) were found. PAPP-A >90th percentile was related to high risk of intrauterine fetal demise (OR 10; 95% CI 2.4-42.5). Both low and high PAPP-A concentrations seem to be related to pregnancy outcome. Further research is needed to investigate evaluation of risk of pregnancy complications according to PAPP-A concentrations as a continuous variable.

Maternal Serum Placental Growth Factor, Soluble Fms-Like Tyrosine Kinase-1, and Soluble Endoglin in Twin Gestations and the Risk of Preeclampsia-A Systematic Review.

Multiple gestation is one of the key risk factors for the occurrence of preeclampsia (PE). Soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin are molecules involved in the process of angiogenesis with a proven role in the pathogenesis of PE. The aim of the review was to summarize available data on maternal serum levels of the above-mentioned factors and their usefulness in predicting PE in twin pregnancies. Only original research articles written in English were considered eligible. Reviews, chapters, case studies, conference papers, experts' opinions, editorials, and letters were excluded from the analysis. No publication date limitations were imposed. The systematic literature search using PubMed/MEDLINE, Scopus, Embase, and Cochrane Library databases identified 338 articles, 10 of which were included in the final qualitative analyses. The included studies showed significant differences in maternal serum levels of the discussed factors between women with twin pregnancies with PE and those who did not develop PE, and their promising performance in predicting PE, alone or in combination with other factors. The identification of the most effective algorithms, their prompt introduction to the clinical practice, and further assessment of the real-life performance should become a priority.

Biomarkers of angiogenesis in twin gestations and the risk of preeclampsia - review of the current literature.

Twin pregnancy is one of the key risk factors for the development of preeclampsia. Soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin are molecules involved in the process of angiogenesis with a proven role in the pathogenesis of preeclampsia. The aim of the review was to summarize available data on maternal serum levels of the biomarkers of angiogenesis and their usefulness in predicting preeclampsia in twin pregnancies. Most of available data suggest biomarkers concentrations differ between singleton and twin gestation and are related to chorionicity of twin pregnancy. Several algorithms including biomarkers of angiogenesis in prediction of PE in twin pregnancy are available and seem promising, however more large prospective surveys are necessary to assess their usefulness in general clinic use.

A three-dimensional map of the Milky Way using classical Cepheid variable stars.

The Milky Way is a barred spiral galaxy, with physical properties inferred from various tracers informed by the extrapolation of structures seen in other galaxies. However, the distances of these tracers are measured indirectly and are model-dependent. We constructed a map of the Milky Way in three dimensions, based on the positions and distances of thousands of classical Cepheid variable stars. This map shows the structure of our Galaxy's young stellar population and allows us to constrain the warped shape of the Milky Way's disk. A simple model of star formation in the spiral arms reproduces the observed distribution of Cepheids.

Sudden Fetal Hematologic Changes as a Complication of Amnioreduction in Twin-Twin Transfusion Syndrome.

We present the first case of a monochorionic twin pregnancy in which sudden hematologic changes occurred as a complication of the amnioreduction procedure for twin-twin transfusion syndrome (TTTS). At 33 weeks of gestation, 4 days after the amnioreduction, the recipient developed severe anemia while the donor developed severe polycythemia. Postnatal placental examination revealed several arteriovenous and venoarterial anastomoses, a pale placental mass of the recipient and a congested and plethoric placental mass of the donor. We speculate on the pathophysiologic changes and potential deleterious effects provoked by the decompressive amnioreduction. Decompression of the placenta and anastomoses after the amnioreduction may have led to an acute blood shift from recipient to donor (thus also a reversal of feto-fetal transfusion), resulting in anemia in the recipient and polycythemia in the donor twin. In the past 15 years, 13 TTTS cases with late presentation were treated with amnioreduction. This is the first time we encountered this severe complication, yielding an incidence of 8%. Although the optimal treatment in TTTS with late presentation is not known, perinatologists should be aware that treatment with amnioreduction can lead to sudden hematologic changes.

No large population of unbound or wide-orbit Jupiter-mass planets.

Planet formation theories predict that some planets may be ejected from their parent systems as result of dynamical interactions and other processes. Unbound planets can also be formed through gravitational collapse, in a way similar to that in which stars form. A handful of free-floating planetary-mass objects have been discovered by infrared surveys of young stellar clusters and star-forming regions as well as wide-field surveys, but these studies are incomplete for objects below five Jupiter masses. Gravitational microlensing is the only method capable of exploring the entire population of free-floating planets down to Mars-mass objects, because the microlensing signal does not depend on the brightness of the lensing object. A characteristic timescale of microlensing events depends on the mass of the lens: the less massive the lens, the shorter the microlensing event. A previous analysis of 474 microlensing events found an excess of ten very short events (1-2 days)-more than known stellar populations would suggest-indicating the existence of a large population of unbound or wide-orbit Jupiter-mass planets (reported to be almost twice as common as main-sequence stars). These results, however, do not match predictions of planet-formation theories and surveys of young clusters. Here we analyse a sample of microlensing events six times larger than that of ref. 11 discovered during the years 2010-15. Although our survey has very high sensitivity (detection efficiency) to short-timescale (1-2 days) microlensing events, we found no excess of events with timescales in this range, with a 95 per cent upper limit on the frequency of Jupiter-mass free-floating or wide-orbit planets of 0.25 planets per main-sequence star. We detected a few possible ultrashort-timescale events (with timescales of less than half a day), which may indicate the existence of Earth-mass and super-Earth-mass free-floating planets, as predicted by planet-formation theories.

The awakening of a classical nova from hibernation.

Cataclysmic variable stars-novae, dwarf novae, and nova-likes-are close binary systems consisting of a white dwarf star (the primary) that is accreting matter from a low-mass companion star (the secondary). From time to time such systems undergo large-amplitude brightenings. The most spectacular eruptions, with a ten-thousandfold increase in brightness, occur in classical novae and are caused by a thermonuclear runaway on the surface of the white dwarf. Such eruptions are thought to recur on timescales of ten thousand to a million years. In between, the system's properties depend primarily on the mass-transfer rate: if it is lower than a billionth of a solar mass per year, the accretion becomes unstable and the matter is dumped onto the white dwarf during quasi-periodic dwarf nova outbursts. The hibernation hypothesis predicts that nova eruptions strongly affect the mass-transfer rate in the binary, keeping it high for centuries after the event. Subsequently, the mass-transfer rate should significantly decrease for a thousand to a million years, starting the hibernation phase. After that the nova awakes again-with accretion returning to the pre-eruption level and leading to a new nova explosion. The hibernation model predicts cyclical evolution of cataclysmic variables through phases of high and low mass-transfer. The theory gained some support from the discovery of ancient nova shells around the dwarf novae Z Camelopardalis and AT Cancri, but direct evidence for considerable mass-transfer changes prior, during and after nova eruptions has not hitherto been found. Here we report long-term observations of the classical nova V1213 Cen (Nova Centauri 2009) covering its pre- and post-eruption phases and precisely documenting its evolution. Within the six years before the explosion, the system revealed dwarf nova outbursts indicative of a low mass-transfer rate. The post-nova is two orders of magnitude brighter than the pre-nova at minimum light with no trace of dwarf nova behaviour, implying that the mass-transfer rate increased considerably as a result of the nova explosion.

Phosphorylated IGFBP-1 in predicting successful vaginal delivery in post-term pregnancy.

PURPOSE: To estimate whether phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretion in term and post-term pregnancies can predict spontaneous onset of labor or vaginal delivery. METHODS: A prospective cohort study of 167 women in singleton term and post-term pregnancies, was conducted at 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, between 2013 and 2014. phIGFBP-1 test (Actim Partus Medix Biochemica), ultrasound cervix assessment and Bishop score were analyzed in the study group. Spontaneous onset of labor was the primary and vaginal delivery was the secondary outcome. RESULTS: In 32.5 % of patients, spontaneous uterine contractions appeared. 67.5 % of women delivered vaginally, 32.5 % had cesarean section. phIGFBP-1 test predicted spontaneous onset of labor (sensitivity 0.69, specificity of 0.42) and successful vaginal delivery (0.67, 0.48). In the prediction of spontaneous delivery onset ultrasound cervical assessment and phIBFBP-1 had comparable sensitivity and in the prediction of successful vaginal birth all three tests had comparable sensitivity. The time from preinduction to spontaneous onset of delivery was significantly shorter in women with positive phIGFBP-1 test (13.65 ± 6.7 vs 20.75 ± 2.6 h; p = 0.006). CONCLUSION: A test for phIGFBP1 presence might be an additional tool for predicting both spontaneous onset of labor and successful vaginal delivery in post-term pregnancies.