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BackgroundIn many diseases, sex differences in diagnostics and therapy play role that is increasingly becoming recognized as important. C-reactive protein (CRP) and white blood cell (WBC) levels are determined as inflammatory markers to detect inflammation and even infection after total shoulder arthroplasty (TSA). The general course of white blood cell, CRP, and hemoglobin (Hb) levels after TSA is well known, but there is insufficient evidence of a possible association with sex. Therefore, we aimed to investigate whether there is an influence of sex on CRP, WBCs, and Hb after TSA in the first 10 days after surgery in a complication-free course in male and female patients and to re-evaluate the specific postoperative CRP, WBC, and Hb course with their maximums (minimum for Hb) and further course until the end of the inpatient period.MethodsWe retrospectively studied patients treated with TSA, reverse shoulder arthroplasty (RSA), and prosthesis replacement between 2015 and 2021. Patients with active inflammation, rheumatoid arthritis, secondary osteoarthritis, active cancer, and documented postoperative complications were not included. CRP, WBC, and Hb levels before shoulder arthroplasty (SA) and up to 10 days after SA were recorded and analyzed for sex differences.ResultsData from a total of 316 patients (209 women and 107 men) were finally analyzed. There were no sex differences in the CRP and WBC values, but women had significantly lower preoperative Hb values, postoperative Hb values, and minimum Hb values. There were no significant differences in Hb, CRP, or WBC levels in the prosthesis exchange group.ConclusionThe progression of CRP and WBC levels showed no sex-specific significant differences after TSA within the first 7 postoperative days. The study confirmed a decreased Hb value for women at all stages of SA. Blood loss was significantly higher for RSA than for TSA for both men and women.

BackgroundPreterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as “brain sparing,” represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation.MethodsWe performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt.ResultsThe mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed.ConclusionOur study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.

BackgroundGender Gap refers to differences between men and women in terms of access to medical education, career development, and leadership positions in medical practice and research. Although women now make up most medical school graduates in many countries, they are often underrepresented in higher positions.ObjectiveThe aim of this study is therefore to analyze the gender-specific development in the field of Obstetrics and Gynecology in Germany over the past 20 years and to survey the current status quo.Materials and methodsAn narrative review was carried out on the development of female graduates of human medicine, the proportion of women in contract medical care and clinical care, as well as the gender-specific evaluation of obtaining a gynecological/obstetric additional qualification. habilitation figures in the field of Obstetrics and Gynecology were evaluated about gender distribution. All data were received from federal institutes.ResultsA total of 46.7% (n = 95,234) of all inpatient doctors were female. A total of 46.7% (n = 95,234) of the physicians in hospitals were female. A total of 46% (1,832/3,958) were the portion of females as assistant physicians, 39.8% (n = 45.551) as specialists, 35.3% (n = 18789) as senior physicians, 25.1% (n = 2394) as first senior physicians and 25% (n = 10) as chief physicians in hospital. A total of 64.6% (n = 3958) of the physicians in Obstetrics and Gynecology were female. A total of 46% (1,832/3,958) were the portion of females as assistant physicians, 64.6% (n = 3958) as specialists, 65.0% (n = 1919) as senior physicians, 26.4% (n = 207) first senior physicians and 25% (n = 10) as chief physicians in Obstetrics and Gynecology.DiscussionThe problem with the gender gap in medicine, does not seem to be access to teaching or starting a residency. But in the functions with increasing responsibility and management functions, e.g., as senior physicians, women are already rarely seen. In Obstetrics and Gynecology, too, there is a shortage of women in leading positions, despite the relatively high numbers, for example as senior physicians. Factors like maternity and establishing a family are points mentioned therefore, but also stereotypes seem to be considerable facts.ConclusionHowever, it is important to recognize the need for more women in higher positions in medicine and actively work to encourage more women to choose a career in medicine.

Abstract Background Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS). The present study aims to assess the vaginal microbial composition of PPROM patients and its development under standard antibiotic therapy and to evaluate the usefulness of the vaginal microbiota for the prediction of EONS. It moreover aims to decipher neonatal microbiota at birth as possible mirror of the in utero microbiota. Methods As part of the PEONS prospective multicenter cohort study, 78 women with PPROM and their 89 neonates were recruited. Maternal vaginal and neonatal pharyngeal, rectal, umbilical cord blood, and meconium microbiota were analyzed by 16S rRNA gene sequencing. Significant differences between the sample groups were evaluated using permutational multivariate analysis of variance and differently distributed taxa by the Mann–Whitney test. Potential biomarkers for the prediction of EONS were analyzed using the MetaboAnalyst platform. Results Vaginal microbiota at admission after PPROM were dominated by Lactobacillus spp. Standard antibiotic treatment triggers significant changes in microbial community (relative depletion of Lactobacillus spp. and relative enrichment of Ureaplasma parvum) accompanied by an increase in bacterial diversity, evenness and richness. The neonatal microbiota showed a heterogeneous microbial composition where meconium samples were characterized by specific taxa enriched in this niche. The vaginal microbiota at birth was shown to have the potential to predict EONS with Escherichia/Shigella and Facklamia as risk taxa and Anaerococcus obesiensis and Campylobacter ureolyticus as protective taxa. EONS cases could also be predicted at a reasonable rate from neonatal meconium communities with the protective taxa Bifidobacterium longum, Agathobacter rectale, and S. epidermidis as features. Conclusions Vaginal and neonatal microbiota analysis by 16S rRNA gene sequencing after PPROM may form the basis of individualized risk assessment for consecutive EONS. Further studies on extended cohorts are necessary to evaluate how far this technique may in future close a diagnostic gap to optimize and personalize the clinical management of PPROM patients. Trial registration NCT03819192, ClinicalTrials.gov. Registered on January 28, 2019.

BackgroundDuring the coronavirus disease 2019 (COVID-19) crisis, many things changed in universities around the world. In-person learning was not possible. Instead, courses were offered in digital form. The sudden change posed enormous challenges to universities, students, and teachers. The aim of this study was to investigate the disadvantages as well as the advantages and opportunities of digital learning.ObjectiveThis study investigated the evaluation of an elective module by medical students and teachers in the traditional in-person and virtual teaching forms during the COVID-19 pandemic.MethodsUsing the elective module “Sports Medicine,” which includes both lectures and practical units, the opinions of the medical students about conventional teaching compared to digital instruction were evaluated. In the winter semester of 2019/2020, all classes were taught face-to-face but had to be switched to virtual teaching in the summer semester of 2020 on an ad hoc basis due to the pandemic. The students were asked to answer questions on general conditions, participant behavior, instructor evaluation, skill acquisition, topic selection, and overall evaluation after both forms of teaching. Likewise, the lecturers of both courses were queried in semiqualitative interviews about the same topics. Descriptive data analysis was performed to process the data.ResultsThe students perceived digital teaching to be superior in most subareas compared to in-person teaching in terms of framework, instructor evaluation, skill acquisition, topic selection, and overall rating. Medical students seemed to feel better with digital teaching in most areas of evaluation. The lecturers found the new form of teaching rather unsettling and criticized the lack of verbal and especially nonverbal communication as well as the short preparation time for the new challenge. The instructors were uncomfortable with some aspects of the virtual teaching format.ConclusionIn the wake of the COVID-19 pandemic, medical schools should rapidly digitize their teaching offerings and support faculty members in their computer-based competence with continuing education opportunities and time resources.

AimTo determine the efficacy of preoperative uterine artery embolization (uterine artery embolization; UAE) prior to elective laparoscopic fibroid removal compared to single laparoscopic fibroid removal in women with large uterine fibroids and women with uterus myomatosus.Material and methodsA total of 202 women with symptomatic uterine fibroids who were scheduled for elective fibroid enucleation were included in this retrospective, monocentric, non-randomized study. Two procedures were compared: women who received percutaneous UAE 24 h prior to elective laparoscopic fibroid eviction for large uterine fibroids (>6 cm) and uterus myomatosus. And women who received laparoscopic fibroid enucleation alone for large uterine fibroids and uterus myomatosus. Outcome parameters for effectiveness were the hospital stay, the operating time and the intraoperative blood loss.ResultsWomen who underwent preoperative percutaneous embolization of the uterine arteries, both for large fibroids and uterus myomatosus, had significantly less blood loss, shorter hospital stays, and shorter operating times.ConclusionsEspecially women with large uterine fibroids and women with uterus myomatosus after having children can benefit from the combination therapy of preoperative percutaneous uterine embolization with subsequent laparoscopic myoma enucleation.

Abstract Metagenomic sequencing is promising for clinical applications to study microbial composition concerning disease or patient outcomes. Alterations of the vaginal microbiome are associated with adverse pregnancy outcomes, like preterm premature rupture of membranes and preterm birth. Methodologically these samples often have to deal with low relative amounts of prokaryotic DNA and high amounts of host DNA (> 90%), decreasing the overall microbial resolution. Nanopore's adaptive sampling method offers selective DNA depletion or target enrichment to directly reject or accept DNA molecules during sequencing without specialized sample preparation. Here, we demonstrate how selective ‘human host depletion’ resulted in a 1.70 fold (± 0.27 fold) increase in total sequencing depth, providing higher taxonomic profiling sensitivity. At the same time, the microbial composition remains consistent with the control experiments. The complete removal of all human host sequences is not yet possible and should be considered as an ethical approval statement might still be necessary. Adaptive sampling increased microbial sequencing yield in all 15 sequenced clinical routine vaginal samples, making it a valuable tool for clinical surveillance and medical-based research, which can be used in addition to other host depletion methods before sequencing.

Abstract Effective perioperative pain management is essential for optimal patient recovery after surgery and reduces the risk of chronification. However, in clinical practice, perioperative analgesic treatment still needs to be improved and data availability for evidence-based procedure specific analgesic recommendations is insufficient. We aimed to identify procedures related with high pain scores, to evaluate the effect of higher pain intensity on patients and to define patient and intervention related risk factors for increased pain after standard gynaecological and obstetrical surgery. Therefore, we performed a prospective cross-sectional study based on the German registry for quality in postoperative pain (QUIPS). A cohort of 2508 patients receiving surgery between January 2011 and February 2016 in our tertiary referral centre (university departments of gynaecology and obstetrics, respectively) answered a validated pain questionnaire on the first postoperative day. Maximal pain intensity was measured by means of a 11-point numeric rating scale (NRS) and related to procedure, perioperative care as well as patient characteristics. The interventions with the highest reported pain scores were laparoscopic removal of ovarian cysts (NRS of 6.41 ± 2.12) and caesarean section (NRS of 6.98 ± 2.08). Factors associated with higher pain intensity were younger age (OR 1.75, 95% CI 1.65–1.99), chronic pain (OR 2.08, 95% CI 1.65–2.64) and surgery performed outside the regular day shift (OR 1.67, 95% CI 1.09–2.36). Shorter duration of surgery, peridural or local analgesic and preoperative sedation reduced postoperative pain. Patients reporting high pain scores (NRS ≥ 5) showed relevant impairment of daily activities and reduced satisfaction. Caesarean section and minimal invasive procedures were associated with the highest pain scores in the present ranking. Pain management of these procedures has to be reconsidered. Younger age, receiving surgery outside of the regular shifts, chronic pain and the surgical approach itself have a relevant influence on postoperative pain intensity. When reporting pain scores of 5 or more, patients were more likely to have perioperative complications like nausea or vomiting and to be impaired in mobilisation. Registry-based data are useful to identify patients, procedures and critical situations in daily clinical routine, which increase the risk for elevated post-intervention pain. Furthermore, it provides a database for evaluation of new pain management strategies.

ObjectiveFacing a shortage of young surgeons, this study aimed to examine the availability of mentoring programs and if this can counteract this lack.Summary background dataMedical mentoring programs have proven to be decisive to influence students’ later career decisions. Since their structure may depend on the medical school and the effort of single disciplines, the offers are often very heterogeneous.MethodsAnonymous online-questionnaires were developed and distributed among medical students in Germany and the dean for teaching of the medical schools from July 2019 to January 2020 in Germany. Data of the availability of mentoring programs, their structure and the impact of surgery were collected.ResultsForty three medical schools participated, with 65% offering mentoring programs. 18 of medical schools had no additional funding available for this. Surgical subjects participated in these programs in only 30%. Additionally, 1,516 medical students participated in the second survey. A total of 70% had already participated in a mentoring program with a significantly higher proportion of men. Of these, 94% stated that this was helpful and had an impact on their career planning, without any gender differences. 95% would participate in structured surgical mentoring programs and 95% agreed that this could have an impact on their career planning.ConclusionMentoring programs may be able to influence career planning, nevertheless participation by surgical specialties has been low. Becoming more active in providing mentoring programs with a special focus on women and offering more surgical content can be a way to counteract the lack of surgical trainees.

Abstract Background Euglycaemic diabetic ketoacidosis (DKA) during pregnancy is a life-threatening obstetric emergency. It requires early identification and prompt action. Obstetricians’ knowledge about symptoms, diagnostic pitfalls and management during pregnancy and delivery need to be improved. We report a case of a young diabetic woman developing severe euglycaemic DKA in two consecutive pregnancies; the first pregnancy resulted in the most deviating outcome (i.e., intrauterine death), while the second pregnancy resulted in the delivery of a healthy newborn. Thus, the novelty of the case presented here is the possibility to demonstrate how the management of DKA in pregnancy can dramatically change outcomes. Case presentation We report a case of a young diabetic woman in whom DKA was concealed by hyperemesis and oesophageal reflux. This woman presented to our delivery unit with severe euglycaemic DKA during her first pregnancy. While the mother’s condition could be successfully stabilized, the foetus died shortly after admission. Two years later, the same woman presented with similar problems. Repeated episodes of mild euglycaemic DKA could be successfully managed with consequent interdisciplinary treatment and close observation, leading to a good pregnancy outcome, i.e., the birth of a healthy child. Conclusion Awareness of euglycaemic DKA needs to be increased to reduce the risk of severe complications during pregnancies in diabetic women. This case report demonstrates that increased awareness of DKA with immediate recognition and a successful multidisciplinary approach are mandatory for an positive pregnancy outcomes.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause, which mainly affects women of childbearing age, especially between 15 and 55 years of age. During pregnancy, SLE is associated with a high risk of perinatal morbidity and mortality. Among the most frequent complications are spontaneous abortion, fetal death, prematurity, intrauterine Fetal growth restriction (FGR), and preeclampsia (PE). The pathophysiology underlying obstetric mortality and morbidity in SLE is still under investigation, but several studies in recent years have suggested that placental dysfunction may play a crucial role. Understanding this association will contribute to developing therapeutic options and improving patient management thus reducing the occurrence of adverse pregnancy outcomes in this group of women. In this review, we will focus on the relationship between SLE and placental insufficiency leading to adverse pregnancy outcomes.

Introduction Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is

Abstract Introduction The NUT midline carcinoma is a rare tumor mostly reported in the midline of upper aerodigestive tract and mediastinum. Children as well as adolescents are affected without a gender distribution. A standard treatment is not established. So far, there exists no reported case of a pregnant female suffering from NUT midline carcinoma with musculoskeletal manifestation. Case presentation A 34-year-old woman was referred to our outpatient clinic by the general practitioner during her 31st week of pregnancy suffering from shoulder pain and dyspnea. So far, dyspnea was interpreted as a typical pregnancy-related symptom. However, a chest X-ray showed a tumor mass in the right lung in close relation to the scapula. Further examinations found metastases in different areas of the body. No pregnancy-related complications were detected by obstetric examination. After an interdisciplinary perinatal case discussion, cesarean section was directly followed by an open biopsy of the right side scapula tumor lesion. A NUT midline carcinoma was diagnosed by immunohistochemistry. Due to disseminated tumor disease in multiple non-resectable locations, a palliative systemical chemotherapy was started by the oncological outpatient clinic. Conclusion This report presents the case of the very rare NUT midline carcinoma under pregnancy which made interdisciplinary case discussions indispensable for therapy planning.

Background Since the COVID-19 pandemic, the demand for online courses has increased enormously. Therefore, finding new methods to improve medical education is imperative. Objective The aim of this study was to compare the self-reports of the individual student-centered virtual teaching techniques (seminar versus fishbowl) in a group of medical students. Methods During the second semester of 2020, students in the clinical phase of the study (n = 144) participated in the optional subject of Sports Medicine. The students were divided into 2 groups. One group (n = 72) received the knowledge transfer in the form of a virtual seminar, the other group (n = 72) in the form of a virtual fishbowl. Results Virtual seminar and virtual fishbowl students gave insights into these teaching techniques. Most of the students from the virtual fishbowl group believed that the virtual fishbowl format allowed them to be more actively involved in learning. The mean quiz scores were statistically higher for students in the virtual fishbowl group than students in the virtual seminar group (p < 0. 001). Conclusion This study concluded that virtual seminars and virtual fishbowl formats could be served as structured learning and teaching formats. At the same time, the virtual fishbowl format can promote an active exchange of knowledge from students’ perspectives.

Introduction: The internet plays an important role as a digital source of information. The aim of this work is to investigate patients with disorder of the female sex organ (malignant and benign) to examine their information behavior about their diseases. The role and importance of the internet as an informative health application for these patients in this context will be highlighted. Materials and methods: This prospective cross-sectional study was based on a survey of patients in Germany during the Coronavirus disease (COVID-19) pandemic among gynecological patients from July 2020 to November 2021. Descriptive statistics were calculated, and simple linear regression analysis was performed to show correlations. Results: We analyzed the responses from 1271 gynecological patients. 91.4% (n = 1162) had an internet-enabled device. Of these, over 55% (n = 644) go online with a smartphone. Only eight percent (n = 101) stated to never feel able to use internet-enabled devices. In addition, almost 47% (n = 596) say that their attitude towards internet-enabled devices changed due the COVID-19 pandemic in a positive way. 82% (n = 1042) of patients can use digital health applications. In addition, more than 82% (n = 1046) believe that the use of digital health applications can have a positive impact on their disease treatment. Due to the COVID-19 pandemic, the attitude towards digital health applications changed positively in 41.4% (n = 526). More than 73% of patients (n = 933) reported using DHAs more frequently. 76% of patients (n = 966) use the internet as a source of information about their gynecological health problem. Over 90% of them (n = 874) regularly use the internet for this purpose. Over 73% of patients (n = 928) state that the internet has become an important source of health information for them since the COVID-19 pandemic. For gynecological problems, two thirds of them (621/928) use the internet as a source of health information before consulting a physician. Conclusion: The internet as an informative digital health application in gynecology is used extensively and is widely accepted by patients. Mistrust of gynecological health information from the internet has diminished because of the COVID-19 pandemic. Confidence in informative digital health applications from the patient's point of view has increased. The internet was seen as a helpful health information platform in addition to medical consultation. More specialized research in the field of e-health in gynecology is needed. This includes large-scale randomized controlled trials, economic analysis, and explorations of user preferences to increase the confidence and usefulness of informative digital health applications in the future. The most reported benefit of the internet as a digital informative health application was time-independent use. The main obstacles were a lack of trust and evidence of the lack of health information from the internet.

Abstract Background To determine the risk of cesarean delivery after labor induction among patients with prior placenta-mediated pregnancy complications (pre-eclampsia, late pregnancy loss, placental abruption or intrauterine growth restriction). Methods The AFFIRM database includes patient level data from 9 randomized controlled trials that evaluated the role of LMWH versus no LMWH during pregnancy to prevent recurrent placenta-mediated pregnancy complications. The primary outcome of this sub-study was the proportion of women who had an unplanned cesarean delivery after induction of labor compared to after spontaneous labor. Results There were 512 patients from 7 randomized trials included in our sub-study. There was no difference in the risk of cesarean delivery between women with labor induction (21/148, 14.2%) and spontaneous labor (79/364, 21.7%) (odds ratio (OR) 0.60, 95% CI, 0.35–1.01; p = 0.052). Among 274 women who used LMWH prophylaxis during pregnancy, the risk of cesarean delivery was lower among those that underwent labor induction (9.8%) compared to spontaneous labor (22.4%) (OR 0.38, 95% CI, 0.17–0.84; p = 0.01). Conclusions The risk of cesarean delivery is not increased after labor induction among a higher risk patient population with prior pregnancy complications. Our results suggest that women who receive LMWH during pregnancy might benefit from labor induction.

Background: Patients suffering from polycystic ovary syndrome (PCOS) are often insulin resistant and at elevated risk for developing gestational diabetes mellitus (GDM). The aim of this study was to explore afamin, which can be determined preconceptionally to indicate patients who will subsequently develop GDM. Serum concentrations of afamin are altered in conditions of oxidative stress like insulin resistance (IR) and correlate with the gold standard of IR determination, the HOMA index. Methods: Afamin serum concentrations and the HOMA index were analyzed post hoc in 63 PCOS patients with live births. Patients were treated at Essen University Hospital, Germany, between 2009 and 2018. Mann–Whitney U test, T test, Spearman’s correlation, linear regression models and receiver-operating characteristic (ROC) analyses were performed for statistical analysis. Results: Patients who developed GDM showed significantly higher HOMA and serum afamin values before their pregnancy (P < 0.001, respectively). ROCs for afamin concentrations showed an area under the curve of 0.78 (95% confidence interval (CI) 0.65–0.90) and of 0.77 (95% CI 0.64–0.89) for the HOMA index. An afamin threshold of 88.6 mg/L distinguished between women who will develop GDM and those who will not with a sensitivity of 79.3% and a specificity of 79.4%. A HOMA index of 2.5 showed a sensitivity of 65.5% and a specificity of 88.2%. Conclusion: The HOMA index and its surrogate parameter afamin are able to identify pre-pregnant PCOS patients who are at risk to develop GDM. Serum afamin concentrations are independent of fasting status and therefore an easily determinable biomarker.

Abstract Background In search of potential early biomarkers for timely prediction of gestational diabetes mellitus (GDM), we focused on afamin, a vitamin E–binding protein in human plasma.. Afamin plays a role in anti-apoptotic cellular processes related to oxidative stress and is associated with insulin resistance and other features of metabolic syndrome. During uncomplicated pregnancy its serum concentrations increase linearly. The aim of this study was to investigate the suitability of afamin as early marker for predicting GDM. Methods In a first-trimester cohort from a prospective observational study of adverse pregnancy outcomes we secondarily analyzed afamin concentrations in 59 patients diagnosed with GDM and 51 controls. Additionally, afamin concentrations were cross-sectionally examined in a mid-trimester cohort of 105 women and compared with results from a simultaneously performed oral glucose tolerance test (OGTT). Subgroup analysis comparing patients treated with either insulin (iGDM) or dietary intervention (dGDM) was performed in both cohorts. Patients were recruited at the University Hospital Essen, Germany, between 2003 and 2016. Results Results were adjusted for body-mass-index (BMI) and gestational age. First and mid-trimester cohorts yielded significantly elevated afamin concentrations in patients with pathological OGTT compared to patients without GDM (first trimester cohort: mean, 113.4 mg/l; 95% CI, 106.4–120.5 mg/l and 87.2 mg/l; 95% CI, 79.7–94.7 mg/l; mid-trimester cohort: mean, 182.9 mg/l; 95% CI, 169.6–196.2 mg/l and 157.3 mg/l; 95% CI, 149.1–165.4 mg/l, respectively). In the first-trimester cohort, patients developing iGDM later in pregnancy presented with significantly higher afamin concentrations compared to patients developing dGDM and compared to patients without GDM. In the mid-trimester cohort, mean concentrations of afamin differed significantly between patients with dGDM compared to controls and between patients with iGDM and controls. Patients with iGDM showed only slightly higher afamin levels compared to patients with dGDM. Conclusion Afamin may serve as a new early biomarker for pathological glucose metabolism during pregnancy. Further research is needed to determine afamin’s concentrations during pregnancy, its predictive value for early detection of pregnancies at high risk to develop GDM and its diagnostic role during the second trimester.

Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm2) of CD45+ leukocytes, CD56+ uNK cells, and CD138+ plasma cells as well as of CD16+ and CD57+ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90–300 CD56+ uNK cells/mm2. uRPL cases were classified in subgroups of low (uRPL-CD56low < 90 cells/mm2), normal (uRPL-CD56normal 90–300 cells/mm2), and high uNK cell counts (uRPL-CD56high > 300 cells/mm2). Some cases from the uRPL-CD56low and uRPL-CD56normal subgroups showed elevated proportions of cytotoxic CD16+ and CD57+ cells in relation to CD56+ cells. In the uRPL-CD56high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.

Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation.

Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4-40.3 weeks of gestation) preclassified in quiet sleep (n = 113, 63 females) and active sleep (n = 286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R(2) of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent fABAS values found in active sleep may reflect alterations in the universal developmental indices, namely fluctuation amplitude, complexity, and pattern formation that constitute fABAS.

BACKGROUND: There is increasing evidence for hormone-dependent modification of function and behavior during the menstrual cycle, but little is known about associated short-term structural alterations of the brain. Preliminary studies suggest that a hormone-dependent decline in brain volume occurs in postmenopausal, or women receiving antiestrogens, long term. Advances in serial MR-volumetry have allowed for the accurate detection of small volume changes of the brain. Recently, activity-induced short-term structural plasticity of the brain was demonstrated, challenging the view that the brain is as rigid as formerly believed. METHODOLOGY/PRINCIPAL FINDINGS: We used MR-volumetry to investigate short-term brain volume changes across the menstrual cycle in women or a parallel 4 week period in men, respectively. We found a significant grey matter volume peak and CSF loss at the time of ovulation in females. This volume peak did not correlate with estradiol or progesterone hormone levels. Men did not show any significant brain volume alterations. CONCLUSIONS/SIGNIFICANCE: These data give evidence of short-term hormone-dependent structural brain changes during the menstrual cycle, which need to be correlated with functional states and have to be considered in structure-associated functional brain research.