KIF2C/MCAK a prognostic biomarker and its oncogenic potential in malignant progression, and prognosis of cancer patients: a systematic review and meta-analysis as biomarker.

KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2Chigh protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2Chigh expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern in vivo and in vitro technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities.

Maternal obesity and placental function: impaired maternal-fetal axis.

The prevalence of maternal obesity rapidly increases, which represents a major public health concern worldwide. Maternal obesity is characteristic by metabolic dysfunction and chronic inflammation. It is associated with health problems in both mother and offspring. Increasing evidence indicates that the placenta is an axis connecting maternal obesity with poor outcomes in the offspring. In this brief review, we have summarized the current data regarding deregulated placental function in maternal obesity. The data show that maternal obesity induces numerous placental defects, including lipid and glucose metabolism, stress response, inflammation, immune regulation and epigenetics. These placental defects affect each other and result in a stressful intrauterine environment, which transduces and mediates the adverse effects of maternal obesity to the fetus. Further investigations are required to explore the exact molecular alterations in the placenta in maternal obesity, which may pave the way to develop specific interventions for preventing epigenetic and metabolic programming in the fetus.

The influence of epidural analgesic techniques on obstetrical outcomes.

PURPOSE: The aim of this study is to compare and evaluate the obstetrical differences between three techniques, including the programmed intermittent epidural bolus (PIEB), the patient-controlled epidural analgesia (PCEA), and the continuous epidural analgesia (CEA). METHODS: This is a retrospective cohort study that investigates the obstetrical outcomes of 2240 patients who received EA during labor in a tertiary maternal unit over the course of 9 years (2011-2018). The only inclusion criterion was the use of epidural analgesia during childbirth and the only exclusion criteria were multiplets' gestation. Multivariate logistic regression, Kruskal-Wallis test, and the log-rank test were utilized to compare the differences between the three EA techniques in terms of cesarean section rate, the incidence of perineal tears, the use of Oxytocin, the duration of labor, and the incidence of paresthesia. RESULTS: Out of the 2240 included deliveries; 1084 utilized PIEB, 1086 PCEA, and 70 CEA techniques. The incidence of Cesarean section was the highest in the CEA group (45.7%) compared to PIEB (24.8%) and PCEA (24.4%) P < 0.001. A significantly shorter duration of labor (vaginal delivery) was observed in the PCEA group (n: 821, 336.7 min) compared to the PIEB group (n: 814, 368.8 min) P < 0.001. There were no statistically significant differences in the incidence of perineal tears, the need of uterotonics, and the incidence of paresthesia. CONCLUSION: The results of this study indicate that the PIEB and PCEA techniques are superior to the CEA technique when it comes to analgesia during childbirth. In this study, the PCEA technique seems to be the best-suited technique for childbirth, since it had a significantly shorter duration of labor than the PIEB technique.

Does overweight and obesity have an impact on delivery mode and peripartum outcome in breech presentation? A FRABAT cohort study.

PURPOSE: Obesity is a worldwide and growing issue affecting women in childbearing age, complicating surgical procedures as well as pregnancy. Through a reduction of not necessarily required cesarean deliveries-for instance in pregnancies with breech presentation-obesity mediated and surgery-associated morbidity might be contained. Date on the impact of maternal BMI in vaginally attempted breech delivery is not existing. To give insight into whether an elevated BMI leads to an increased perinatal morbidity in vaginally intended deliveries out of breech presentation, we analyzed delivery outcome of laboring women with a singleton baby in breech presentation with overweight and obesity (BMI ≥ 25 kg/m2) in comparison to women with a BMI of below 25 kg/m2. METHODS: Based on data from January 2004 to December 2020, a cohort study was performed on 1641 women presenting with breech presentation at term (> 37 weeks). The influence of maternal BMI on perinatal outcome was analyzed with Chi2 testing for group differences and logistic regression analysis. Patients with a hyperglycemic metabolism were excluded from the study. RESULTS: Fetal morbidity was not different when patients with a BMI of ≥ 25 kg/m2 (PREMODA morbidity score 2.16%) were compared to patients with a BMI of below 25 kg/m2 (1.97%, p = 0.821). Cesarean delivery rates were significantly higher in overweight and obese women with 43.9% compared to 29.3% (p < 0.0001). BMI and cesarean delivery were significantly associated in a logistic regression analysis (Chi2 coefficient 18.05, p < 0.0001). In successful vaginal deliveries out of breech presentation, maternal perineal injury rates (vaginal birth in normal-BMI women 48.4%; vaginal birth in overweight and obese women: 44.2%; p = 0.273) and rates of manually assisted delivery (vaginal birth in normal-BMI women: 44.4%; vaginal birth in obese and overweight women: 44.2%; p = 0.958) were not different between BMI groups. CONCLUSIONS: Obesity and overweight are not associated with peripartum maternal or newborn morbidity in vaginally attempted breech delivery, if the patient cohort is thoroughly selected and vaginal breech delivery is in an upright maternal position. Reduction of cesarean delivery rates, especially in overweight and obese women might, have an important positive impact on maternal and newborn morbidity.

The association between gynecological complaints and the uterine sonographic features in women with a history of cesarean section.

PURPOSE: The aim of this study is to investigate the association between post-cesarean sonographic uterine measures, dysmenorrhea, and bleeding disorders. METHODS: This is a cross-sectional study where 500 women with a history of only one cesarean section (CS) were recruited. A transvaginal transducer, GE RIC6-12-D was used for the acquisition of volumetric datasets 18 ± 7 months postpartum. Uterine length (UL), cervical length (CL), niche length (L), niche depth (D), niche width (W), fibrosis length (FL), fibrosis depth (FD), residual myometrial thickness (RMT), endometrial thickness (EM), scar to internal os distance (SO), anterior myometrial thickness superior (sAMT) and inferior (iAMT) to the scar, and the posterior myometrial thickness opposite the scar (PMT), superior (sPMT), and inferior to it (iPMT) were measured. Logistic regression with odds ratios (OR), 95% confidence intervals (CI) and ROC curves were utilized. RESULTS: The proportion of patients with incident post-cesarean bleeding disorders and dysmenorrhoea was 36% (CI 32%, 40%) and 17% (CI 14%, 21%) respectively. Univariate logistic regression showed that only UL was associated with bleeding disorders [OR 1.04 (CI 1.01,10.7) p value 0.005], whereas dysmenorrhea was associated with RMT [OR 0.82 (CI 0.71,0.95) p value 0.008], SO [OR 0.91 (CI 0.86,0.98) p value 0.01], and RMT ratio [OR 0.98 (CI 0.97,0.99) p value 0.03]. Multivariate logistic regression for dysmenorrhoea including SO and RMT remains statistically significant with p values <0.05 and area under the curve of 0.66. CONCLUSION: There is an association between sonographic appearance of CS scars and dysmenorrhoea. Nevertheless, the association is weak and other biological post-cesarean characteristics should be explored as potential causes.

Sonographic examination at the beginning of the second stage of labor predicts birth outcome in vaginally intended breech deliveries: a blinded prospective study.

PURPOSE: In order to spread competence in vaginal breech deliveries, it is necessary to develop new and easily applicable tools for birth progression and safety evaluation. Ultrasound is a useful and ubiquitously available tool with already documented value for birth progression observation. In deliveries out of breech presentation, an established ultrasound examination is missing. We determined the descent of the fetal buttocks in relation to the maternal pelvic inlet using intrapartum ultrasound. We evaluated these results in comparison to the clinical vaginal examination with the aim to establish an easily applicable method for birth outcome prediction. Therefore, we analyzed the predictive value of our examinations on birth outcome parameters, such as cesarean section rate, as well as fetal and maternal outcome parameters. METHODS: We performed a prospective blinded study on 106 mothers with vaginally intended breech delivery. At beginning of stage two in labor, the descent of the fetal buttocks into the mother's pelvic inlet was detected with transabdominal ultrasound and vaginal examination by different observers. PRIMARY OUTCOME VARIABLE: Cesarean section rate. Secondary outcome variables: rate of manual assistance in vaginal deliveries, birth duration, 5' APGAR score, umbilical arterial pH, maternal blood loss, and perineal injury. For non-parametric values, Wilcoxon's χ2 test was performed. In order to analyze the predictive value of our examination, lack-of-fit analysis was conducted. Reliability evaluation of the sonographic examination was done with a matched-pair analysis. RESULTS: Women with positive intrapartum ultrasound breech engagement sign (+ IPUBES) had a significantly lower rate of cesarean section in comparison with those with negative IPUBES (5/67; 7.5% vs. 18/39; 46.2%; p < 0.0001). The area under the ROC curve for the prediction of CS for negative IPUBES was 0.765 with a sensitivity of 78.3% and a specificity of 74.7%. Sonographic examination showed an excellent reliability in a matched-pair analysis comparing vaginal and sonographic examinations with a mean difference of 0.012 (SD ± 0.027, 95% CI - 0.014 to 0.065). Mean birth duration was significantly longer in deliveries with negative IPUBES (533 min vs. 440 min; p = 0.0011). Fetal and maternal outcome parameters were not significantly different between deliveries with positive and negative IPUBES. CONCLUSIONS: Sonographic evaluation of the fetal descent in relation to the mother's pelvic inlet screens reliably for emergency cesarean section. This newly presented method for birth progression observation might be a powerful tool for distribution of expertise in vaginal breech delivery and is able to give reference for clinical vaginal examination by obstetricians in training. TRAIL REGISTRY: Clinical trial. Date of registration: 13.03.2019; Date of initial participant enrollment: 20.03.2019; DRKS00016885; https://www.drks.de ; German clinical trials register.

The impact of selective episiotomy on maternal short-term morbidity: a retrospective study.

BACKGROUND: The aim is to investigate the risk of short-term maternal morbidity caused by the selective clinical use of episiotomy (rate < 0.02), and to compare the risk of severe perineal tears with the statewide risk. METHODS: In this retrospective cohort study, we investigated the effect of selective episiotomy on the risk of severe perineal tears and blood loss in singleton term deliveries, using propensity scores with inverse probability weighting. RESULTS: This study included 10992 women who delivered vaginally between 2008-2018. Episiotomy was performed in 171 patients (1.55%), three of whom (1.75%) experienced severe perineal tears compared to 156 (1.44%) in the control cohort. The adjusted odds ratio of severe perineal tears was 2.06 (95% confidence interval [CI]: 0.51, 8.19 with 0.3 p value). Multivariate linear regression showed that episiotomy increased blood loss by 96.3 ml (95% CI: 6.4, 186.2 with 0.03 p value). Episiotomy was performed in 23% (95% CI: 0.228, 0.23) of vaginal deliveries in the state of Hessen, with a risk of severe perineal tears of 0.0143 (95% CI: 0.0139, 0.0147) compared to 0.0145 (95% CI: 0.0123, 0.0168) in our entire cohort. CONCLUSIONS: Selective use of episiotomy does not increase the risk of higher-grade perineal tears. However, it may be associated with maternal morbidity in terms of increased blood loss.

An episiotomy is a cut between the vagina and the anus that may be performed by an obstetrician during childbirth and can result in increased blood loss or severe birth tears. In this study, we investigated the risks of both bleeding and severe tears caused by a highly selective local practice of episiotomies below 2% and compared the results with statewide data. The study included 10992 women who delivered between 2008­2018, 171 of whom underwent episiotomies according to the hospital's protocols. Having an episiotomy did not increase the likelihood of severe birthing tears but was associated with an increase in estimated blood loss. Therefore, although highly selective use of episiotomy is unlikely to cause more severe tears, it has the potential to worsen the mother's health by increasing blood loss.

The influence of epidural anesthesia in pregnancies with scheduled vaginal breech delivery at term: a hospital-based retrospective analysis.

INTRODUCTION: Epidural anesthesia is a well-established procedure in obstetrics for pain relief in labor and has been well researched as it comes to cephalic presentation. However, in vaginal intended breech delivery less research has addressed the influence of epidural anesthesia. The Greentop guideline on breech delivery states that there's little evidence and recommends further evaluation. OBJECTIVE: The aim of this study was to compare maternal and neonatal outcomes in vaginally intended breech deliveries at term with and without an epidural anesthesia. DESIGN: This study was a retrospective cohort study. SAMPLE: This study included 2122 women at term with a singleton breech pregnancy from 37 + 0 weeks of pregnancy on and a birth weight of at least 2500 g at the obstetric department of University hospital Frankfurt from January 2007 to December 2018. METHODS: Neonatal and maternal outcome was analyzed and compared between women receiving "walking" epidural anesthesia and women without an epidural anesthesia. RESULTS: Fetal morbidity, measured with a modified PREMODA score, showed no significant difference between deliveries with (2.96%) or without (1.79%; p = 0.168) an epidural anesthesia. Cesarean delivery rates were significantly higher in deliveries with an epidural (35 vs. 26.2%, p = 0.0003), but after exclusion of multiparous women, cesarean delivery rates were not significantly different (40.2% cesarean deliveries with an epidural vs. 41.5%, p = 0.717). As compared to no epidurals, epidural anesthesia in vaginal delivery was associated with a significantly higher rate of manual assistance (33.8 versus 52.1%) and a longer duration of birth (223.7 ± 194 versus 516.2 ± 310 min) (both p < 0.0001)". CONCLUSION: Epidural anesthesia can be offered as a safe option for pain relief without increasing neonatal or maternal morbidity and mortality. Nevertheless, it is associated with a longer birth duration and manually assisted delivery.

Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia.

BACKGROUND: The development of the human placenta is tightly coordinated by a multitude of placental cell types, including human chorionic villi mesenchymal stromal cells (hCV-MSCs). Defective hCV-MSCs have been reported in preeclampsia (PE), a gestational hypertensive disease characterized by maternal endothelial dysfunction and systemic inflammation. Our goal was to determine whether hCV-MSCs are ciliated and whether altered ciliation is responsible for defective hCV-MSCs in preeclamptic placentas, as the primary cilium is a hub for signal transduction, which is important for various cellular activities. METHODS: In the present work, we collected placental tissues from different gestational stages and we isolated hCV-MSCs from 1st trimester, term control, and preeclamptic placentas. We studied their ciliation, functionality, and impact on trophoblastic cell lines and organoids formed from human trophoblast stem cells (hTSCs) and from the trophoblastic cell line JEG-3 with various cellular and molecular methods, including immunofluorescence staining, gene analysis, spheroid/organoid formation, motility, and cellular network formation assay. The statistical evaluation was performed using a Student's t test (two-tailed and paired or homoscedastic) or an unpaired Mann-Whitney U test (two-tailed). RESULTS: The results show that primary cilia appeared abundantly in normal hCV-MSCs, especially in the early development of the placenta. Compared to control hCV-MSCs, the primary cilia were truncated, and there were fewer ciliated hCV-MSCs derived from preeclamptic placentas with impaired hedgehog signaling. Primary cilia are necessary for hCV-MSCs' proper signal transduction, motility, homing, and differentiation, which are impaired in preeclamptic hCV-MSCs. Moreover, hCV-MSCs derived from preeclamptic placentas are significantly less capable of promoting growth and differentiation of placental organoids, as well as cellular network formation. CONCLUSIONS: These data suggest that the primary cilium is required for the functionality of hCV-MSCs and primary cilia are impaired in hCV-MSCs from preeclamptic placentas.

Giving birth alone due to COVID-19-related hospital restrictions compared to accompanied birth: psychological distress in women with caesarean section or vaginal birth - a cross-sectional study.

OBJECTIVES: We examined the mental health of mothers after unaccompanied birth (unaccompanied group, UG) due to COVID-19-related visiting bans and compared the data with a control group with accompanied birth (AG). Additionally, a distinction was made between caesarean section (CS) and vaginal birth (VB), as existing research indicates a higher risk for mental distress after CS. METHODS: The cross-sectional study included 27 mothers in the UG and 27 matched controls (AG). Anxiety, depression, postpartum traumatic stress symptoms (PTSS), and psychological well-being were assessed. Additionally, emotions and attitudes related to the restrictions were measured by self-developed items. RESULTS: Psychological distress was high especially in the UG (anxiety: 23%, PTSS: 34.6%, low well-being: 42.3%, depression: 11.5%). Mothers in the AG had lower psychological distress than those in the UG, but still had enhanced rates of PTSS (11.1%) and diminished well-being (22.2%). In both groups, women with CS reported higher anxiety and trauma scores and lower well-being than women with VB. Unaccompanied mothers with CS perceived visitation restrictions as less appropriate and felt more helpless, angry, worried, and frustrated about the partner's absence than women with VB. CONCLUSIONS: The partner's absence during, but also after childbirth has a major impact on psychological outcomes. Particularly, higher rates of anxiety and PTSS can lead to negative consequences for mothers and their children. Therefore, it is strongly recommended to relax visitation bans and avoid unaccompanied births. Psychological treatment in obstetric units is more urgently needed than ever, especially for women with a caesarean section.

Ectopic pregnancy: a single-center experience over ten years.

PURPOSE: The aim of this study was to investigate characteristics associated with ectopic pregnancy (EP) that could be utilized for predicting morbidity or mortality. METHODS: This was a retrospective analysis of pregnancy-related records from a tertiary center over a period of ten years. Data on age, gravidity, parity, EP risk, amenorrhea duration, abdominal pain presence and location, ß-human chorionic gonadotropin (ß-HCG) level, ultrasound findings, therapeutic intervention, exact EP implantation site and length of hospital stay (LOS) were obtained from the database. The LOS was used as a proxy for morbidity and was tested for an association with all variables. All statistical analyses were conducted with Stata® (ver. 16.1, Texas, USA). RESULTS: The incidence of EP in a cohort of 30,247 pregnancies over a ten-year period was 1.05%. Patients presented with lower abdominal pain in 87.9% of cases, and the likelihood of experiencing pain was tenfold higher if fluid was detectable in the pouch of Douglas. Only 5.1% of patients had a detectable embryonic heartbeat, and 18.15% had one or more risk factors for EP. While most EPs were tubal, 2% were ovarian. The LOS was 1.9 days, and laparoscopic intervention was the main management procedure. The cohort included one genetically proven dizygotic heterotopic pregnancy (incidence, 3.3 × 10- 5) that was diagnosed in the 7th gestational week. The only association found was between the ß-HCG level and LOS, with a linear regression ß coefficient of 0.01 and a P-value of 0.04. CONCLUSION: EP is a relatively common condition affecting approximately 1% of all pregnancies. ß-HCG correlates with EP-related morbidity, but the overall morbidity rate of EP is low regardless of the implantation site. Laparoscopic surgery is an effective therapeutic procedure that is safe for managing EP, even in cases of heterotopic pregnancy.

Does the appearance of the cutaneous scar after cesarean section reflect the residual myometrial thickness?

PURPOSE: The aim of this study is to utilize the Manchester scar scale (MSS) and ultrasound in investigating the association between uterine wall defects and cutaneous scar characteristics after cesarean section (CS). METHODS: This is a prospective cohort study. The degree of myometrial loss was quantified by calculating a residual myometrial thickness (RMT) ratio as a percentage of RMT to the pre-cesarean anterior uterine wall thickness. Cutaneous scar assessment was performed according to the MSS. Spearman's correlation and the Kruskal-Wallis test with a cut-off value of p < 0.05 were used for statistical analysis. RESULTS: Two hundred forty seven women, of which 2.4% had an Asian, 3.6% an Afro-American, 82% a Caucasian and 12% a Mediterranean background, were recruited. The RMT ratio ranged between 11.9 and 100% with a median of 55.8% and an average of 56%. MSS scores ranged from 4 to 13 with a median of 5 and an average of 6. Spearman's correlation between MSS and RMT ratio show a rho of - 0.01 with a p value of 0.8. The correlation between MSS and RMT ratio within the four ethnical groups showed a p value between 0.3 and 0.8 and a rho between 0.8 and - 0.8. The Kruskal-Wallis test showed an eta2 of 0.13 and a p value of 0.0002 for the effect of ethnicity on MSS and an eta2 of 0.009 and a p value of 0.68 for the effect of ethnicity on the RMT ratio. CONCLUSION: CS laparotomy scars heal differently between ethnical groups, but generally with satisfying results. Ethnicity does not affect myometrial healing and scar appearance does not reflect myometrial healing after CS. Thus, separate uterine sonographic assessment is recommended.

Anatomy of the sonographic post-cesarean uterus.

PURPOSE: We aim to describe the sonographic uterine anatomy after a cesarean section (CS), test the reproducibility of predefined measurements from the BSUM study, and report the distribution of these measurements. METHODS: This is a descriptive observational study where 200 women with a history of only one CS were recruited 12-24 months postoperatively. A 5-13 MHz micro-convex transvaginal transducer was used for the acquisition of volumetric datasets for evaluating the CS scars. We defined 15 distinct measurements including the residual myometrial thickness (RMT). RMT ratio was calculated as a percentage of RMT to the assumed pre-cesarean anterior uterine wall thickness. A P value below 0.05 is utilized for significant statistical analysis. RESULTS: Patients were included on average 18.5 months post-cesarean. The uterus was anteflexed in 82.5% and retroflexed in 17.5%. Myometrial defects at the site of CS manifest in two forms, either as a niche or as fibrosis. Patients are classified into four groups: those with isolated niches (45%), combined niches and fibrosis (38.5%), isolated fibrosis (11%), and lacking both (5%). The median RMT ratio for these groups was 63.09, 40.93, 59.84, and 100% with a standard deviation of 16.73, 12.95, 16.59, and 0, respectively. The interclass correlation coefficient (ICC) remained above 0.9 for all distinct measurements among these groups except for those of RMT, where ICC varied between 0.47 and 0.96. The RMT ratio shows a constant ICC at 0.94 regardless of the group. CONCLUSION: The post-cesarean uterus is often anteflexed, and a myometrial loss of about 50% is normally expected. The pattern of this loss is in the form of a predominantly sharp-edged and echogenic niche, fibrosis, or a combination of both. The proposed RMT ratio takes these changes into consideration and results in a reproducible quantification. We hypothesize that different adverse outcomes could be attributed to the different scar patterns.

The B-mode sonographic evaluation of the post-caesarean uterine wall and its methodology: A study protocol.

AIM: The aim of this study is to utilize the niche measurement guidelines outlined by Jordans et al. in order to establish normal values and accurate description of caesarean section scars in a normal population. After defining the normal distribution, abnormal pregestational scar characteristics will be identified for predicting adverse pregnancy outcomes. METHODS: This is a prospective observational multicenter clinical study where women with a history of only one caesarean section and yet open family planning are enrolled. The uterine length, cervical length, niche length, niche depth, niche width, residual myometrial thickness, endometrial thickness, scar to internal os distance, anterior myometrial thickness superior and inferior to the scar and the posterior myometrial thickness opposite the scar, superior and inferior to it are measured in a pregestational uterus. The lower uterine segment is measured over a length of 3 cm during subsequent pregnancy and followed up until delivery. RESULTS: Data from 500 patients will yield normal distribution curves for all predefined measurements. Establishing a correlation between deviations from the normal measures and adverse events would be instrumental for counseling women regarding subsequent pregnancy and mode of delivery. CONCLUSION: This study will demonstrate the changes of the post-caesarean scar from a non-pregnant uterus until delivery and can confirm the importance of the scar characteristics in predicting pregnancy outcome.

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics.

The coronavirus disease 2019 COVID-19 pandemic is rapidly spreading worldwide and is becoming a major public health crisis. Increasing evidence demonstrates a strong correlation between obesity and the COVID-19 disease. We have summarized recent studies and addressed the impact of obesity on COVID-19 in terms of hospitalization, severity, mortality, and patient outcome. We discuss the potential molecular mechanisms whereby obesity contributes to the pathogenesis of COVID-19. In addition to obesity-related deregulated immune response, chronic inflammation, endothelium imbalance, metabolic dysfunction, and its associated comorbidities, dysfunctional mesenchymal stem cells/adipose-derived mesenchymal stem cells may also play crucial roles in fueling systemic inflammation contributing to the cytokine storm and promoting pulmonary fibrosis causing lung functional failure, characteristic of severe COVID-19. Moreover, obesity may also compromise motile cilia on airway epithelial cells and impair functioning of the mucociliary escalators, reducing the clearance of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Obese diseased adipose tissues overexpress the receptors and proteases for the SARS-CoV-2 entry, implicating its possible roles as virus reservoir and accelerator reinforcing violent systemic inflammation and immune response. Finally, anti-inflammatory cytokines like anti-interleukin 6 and administration of mesenchymal stromal/stem cells may serve as potential immune modulatory therapies for supportively combating COVID-19. Obesity is conversely related to the development of COVID-19 through numerous molecular mechanisms and individuals with obesity belong to the COVID-19-susceptible population requiring more protective measures.

The Function of Oncogene B-Cell Lymphoma 6 in the Regulation of the Migration and Invasion of Trophoblastic Cells.

Human placentation is a highly invasive process. Deficiency in the invasiveness of trophoblasts is associated with a spectrum of gestational diseases, such as preeclampsia (PE). The oncogene B-cell lymphoma 6 (BCL6) is involved in the migration and invasion of various malignant cells. Intriguingly, its expression is deregulated in preeclamptic placentas. We have reported that BCL6 is required for the proliferation, survival, fusion, and syncytialization of trophoblasts. In the present work, we show that the inhibition of BCL6, either by its gene silencing or by using specific small molecule inhibitors, impairs the migration and invasion of trophoblastic cells, by reducing cell adhesion and compromising the dynamics of the actin cytoskeleton. Moreover, the suppression of BCL6 weakens the signals of the phosphorylated focal adhesion kinase, Akt/protein kinase B, and extracellular regulated kinase 1/2, accompanied by more stationary, but less migratory, cells. Interestingly, transcriptomic analyses reveal that a small interfering RNA-induced reduction of BCL6 decreases the levels of numerous genes, such as p21 activated kinase 1, myosin light chain kinase, and gamma actin related to cell adhesion, actin dynamics, and cell migration. These data suggest BCL6 as a crucial player in the migration and invasion of trophoblasts in the early stages of placental development through the regulation of various genes associated with the migratory machinery.

Communication and patient safety in gynecology and obstetrics - study protocol of an intervention study.

BACKGROUND: Patient safety is a key target in public health, health services and medicine. Communication between all parties involved in gynecology and obstetrics (clinical staff/professionals, expectant mothers/patients and their partners, close relatives or friends providing social support) should be improved to ensure patient safety, including the avoidance of preventable adverse events (pAEs). Therefore, interventions including an app will be developed in this project through a participatory approach integrating two theoretical models. The interventions will be designed to support participants in their communication with each other and to overcome difficulties in everyday hospital life. The aim is to foster effective communication in order to reduce the frequency of pAEs. If communication is improved, clinical staff should show an increase in work satisfaction and patients should show an increase in patient satisfaction. METHODS: The study will take place in two maternity clinics in Germany. In line with previous studies of complex interventions, it is divided into three interdependent phases. Each phase provides its own methods and data. Phase 1: Needs assessment and a training for staff (n = 140) tested in a pre-experimental study with a pre/post-design. Phase 2: Assessment of communication training for patients and their social support providers (n = 423) in a randomized controlled study. Phase 3: Assessment of an app supporting the communication between staff, patients, and their social support providers (n = 423) in a case-control study. The primary outcome is improvement of communication competencies. A range of other implementation outcomes will also be assessed (i.e. pAEs, patient/treatment satisfaction, work satisfaction, safety culture, training-related outcomes). DISCUSSION: This is the first large intervention study on communication and patient safety in gynecology and obstetrics integrating two theoretical models that have not been applied to this setting. It is expected that the interventions, including the app, will improve communication practice which is linked to a lower probability of pAEs. The app will offer an effective and inexpensive way to promote effective communication independent of users' motivation. Insights gained from this study can inform other patient safety interventions and health policy developments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03855735; date of registration: February 27, 2019.

The uterine fibroid/myoma tumour: analysis of the global research architecture using density-equalizing mapping.

Uterine fibroids can severely impact a woman's quality of life, result in significant morbidity and are a leading indication for hysterectomy. Many aspects of the disease remain largely obscure. Despite these knowledge gaps, no detailed maps of the global fibroid research architecture have yet been generated. This study used the NewQIS approach to assess worldwide research productivity, encompassing numerous aspects of the scientific output, quality and socioeconomic features. Regression analysis indicated an increase in fibroid research activity in the investigated time periods. Global research output was dominated by leading Western countries, with the USA at the forefront, but also by East Asian countries. Socioeconomic benchmarking revealed that Taiwan had the highest fibroid research activity per GDP, with a calculated average of 279.46 fibroid-related publications per 1000 billion USD GDP. Finland was the most active country with respect to research activity per population size. Subject area analyses revealed major differences in research focuses, for example 'Radiology, Nuclear Medicine and Medical Imaging' was assigned to 29.92% of South Korean and to only 10.38% of US-American publications. In conclusion, this analysis of global fibroid research activity illustrates a multitude of important features ranging from quantitative and semi-qualitative fibroid research aspects to socioeconomic benchmarking.

Correction to: World-wide research architecture of vitamin D research: density-equalizing mapping studies and socio-economic analysis.

After publication of the original article [1], the authors reported two errors which needed to be corrected.

World-wide research architecture of vitamin D research: density-equalizing mapping studies and socio-economic analysis.

BACKGROUND: Despite the numerous associations of vitamin D with health and disease, vitamin D deficiency is still common from a global perspective. While basic research, clinical and preventive activities grow constantly in vitamin D research, there is no in-depth analysis of the related global scientific productivity available so far. METHODS: Density equalizing mapping procedures (DEMP) were combined with socioeconomic benchmarks using the NewQIS platform. RESULTS: A total of 25,992 vitamin D-related research articles were identified between 1900 to 2014 with a significant increase (r2 = .6541) from 1900 to 2014. Authors located in Northern America - especially in the USA - distributed the majority of global vitamin D research, followed by their Western European counterparts. DEMP-analysis illustrates that Africa and South America exhibit only minor scientific productivity. Among high-income group countries, Scandinavian nations such as Denmark or Finland (2147.9 and 1607.7 vitamin D articles per GDP in 1000 billion USD) were highly active with regard to socioeconomic figures. CONCLUSION: Networks dedicated to vitamin D research are present around the world. Overall, the Northern American and Western European nations occupy prominent positions. However, South American, African and Asian countries apart from Japan only play a minor role in the global research production related to vitamin D. Since vitamin D deficiency is currently increasing in the Americas, Europe and parts of the Middle East, research in these regions may need to be encouraged.