MiRNA-mRNA integrative analysis reveals epigenetically regulated and prognostic miR-103a with a role in migration and invasion of carboplatin-resistant ovarian cancer cells that acquired mesenchymal-like phenotype.

BACKGROUND: DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response. PURPOSE: Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype. METHODS: MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values. RESULTS: MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a-3p, miR-17-5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a-3p was epigenetically regulated at the constitutive level. CONCLUSION: High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential.

Overactive Bladder or Anxiety: Which Came First?

OBJECTIVE: Although available diagnostic criteria are intelligible, combination of OAB and anxiety in the same patient presents a perfect example of medical causality dilemma, commonly stated as the question: "which came first: the chicken or the egg?". The aim of this review article is to address available insights in bidirectional association between OAB and anxiety. METHODS: In this review article, we included different types of studies whose results are presented as relative risk (RR) or odds ratio (OR) with a 95% accuracy. A literature search was conducted with the use of the PubMed and EMBASE electronic databases focusing on identifying articles published in English between 1990 and 2020. RESULTS: The electronic searches, after duplicate records removal, provided a total of 126 citations. Of these, 107 were excluded after title/abstract screening (not relevant to the review). We examined the full text of 19 publications remaining to summarize possible mechanisms between OAB and anxiety. According to examined literature, our result synthesis provides insight in epidemiology, pathophysiology, diagnostic and therapeutic approach of both conditions. CONCLUSION: Temporal relationship between OAB and anxiety is not very well documented because available longitudinal cohort studies are limited. The limitation of the published literature is that most were population-based symptom studies demonstrating high risk of bias. Although data from analysed studies suggest that anxiety and OAB and anxiety might be casually related, studies provided on clinical population are warranted. In addition to the traditional urologic factors, we recommend that psychosocial factors such as anxiety should be assessed routinely in patients with OAB.

Maternity Blues among Croatian Mothers - A Single-Center Study.

BACKGROUND: Maternity blues is a transient change of mood that occurs within the first few days after delivery. Some of the most common symptoms include mood swings, tearfulness, irritability, loss of appetite, fatigue. The aim of the study was to investigate the relationship between maternity blues, psychological, demographic and obstetrics risk factors. SUBJECTS AND METHODS: A cross-sectional study was conducted between October 2019 and February 2020 at the University Hospital Center Zagreb, Croatia. Final analysis included 227 mothers. Participants were assessed with Stein's Maternity Blues Scale, Connor-Davidson Resilience Scale (CD-RISC), Multidimensional Scale of Perceived Support (MSPSS) and Brennan's Experiences in Close Relationship Scale, as well as demographic and obstetric data. RESULTS: The prevalence of maternity blues in our study was 19.9%. Higher result on Stein's Maternity Blues Scale was associated with anxious attachment style (r=0.425, p<0.01), oxytocin (r=0.308, p<0.01), lower birth weight (r=-0.242), lower resilience (r=-0.252) and less perceived social support from family and significant other (p<.01). CONCLUSIONS: This report presents the very first study assessing maternity blues occurence among Croatian mothers and in Croatian cultural environment. We believe that our report will address importance of employing adequate screening methods in preventing and timely recognizing maternity blues and subsequent postpartum depression in Croatian population.

Comparison of efficacy of extracorporeal magnetic innervation and Kegel exercises for stress urinary incontinence in adult women: study protocol for a randomized controlled trial.

Stress urinary incontinence (SUI) is defined as a complaint of inadvertent loss of urine occurring as a result of an increase in intraabdominal pressure. Strong evidence supports the use of pelvic floor muscle training (PFMT) as the first-line conservative treatment for SUI. Extracorporeal magnetic stimulation (EMS) is a non-invasive, effective, acceptable, and safe therapeutic modality for SUI. Although PFMT and EMS share most of their influences on the pathophysiology of SUI, it is unclear whether one of these routinely used treatment modalities is superior to another in terms of improvement of clinical outcomes or cost-effectiveness. To the best of our knowledge, no randomized controlled trials have so far directly compared PFMT with EMS. Our aim here is to describe a protocol for such a study. This will be a parallel-group, single-blind, randomised controlled trial compliant with the SPIRIT, CONSORT, and TIDieR reporting guidelines. Participants will be women aged 18 to 65 years who have previously given at least one vaginal delivery (at least 12 months before joining the study) who present with symptoms of SUI lasting at least 6 months yet have not previously received treatment for it. In the first study arm, patients will receive an eight-week, high-intensity, home-based Kegel exercises regimen. In the second study arm, the treatment scheme will consist of 2 sessions of EMS per week for a total of eight weeks. The primary outcome will be effectiveness of treatment as measured by the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form overall score, eight weeks, three months, and six months after commencement of treatment.

Validation of the UDI-6 and the ICIQ-UI SF - Croatian version.

INTRODUCTION AND HYPOTHESIS: Despite the widespread use of UDI-6 and ICIQ-UI SF in Croatia, it remains unknown whether a realiable and valid measure for the population of interest is used. Thus, the aim of this study was to translate, adapt and validate the UDI-6 and the ICIQ-UI SF in Croatia. METHODS: The study included a total of 232 consecutive patients with urinary incontinence symptoms. The translation to Croatian followed standardized procedure. All participants underwent urodynamic assesment and completed UDI-6 and ICIQ-UI SF questionnaires at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated in order to assess internal consistency. RESULTS: Both questionnaires had high internal consistency (Cronbach α for UDI-6 and ICIQ-UI SF was .83 and .85, respectively) and high test-retest reliability (intraclass correlation coefficient .99 for instruments). Strong correlation was found between urodynamic findings and total scores in UDI-6 and ICIQ-UI SF (ρ = 0.88 and 0.89, respectively). Women with stress urinary incontinence (SUI) and detrusor overactivity (DOA) group had significantly higher scores on UDI-6 (Mdn = 33.33 and Mdn = 50, respectively) compared to women with no urodynamic abnormality (Mdn = 0; p < 0.001). Women with no urodynamic abnormality scored significantly lower on ICIQ-UI SF (Mdn = 0; p < 0.001) compared to women with SUI (Mdn = 14) and DOA (Mdn = 16). Women with DOA scored worse on Irritative and Obstructive symptoms when comparing with two other groups (p < 0.001), while women with SUI had significantly worse score on Stress symptoms subscale (p < 0.001). CONCLUSIONS: The UDI-6 and ICIQ-UI SF have very good psychometric characteristics and can be used in Croatian urogynecology practice.

A 27-year-old patient with congenital bladder exstrophy and recurrent pelvic organ prolapse: a case report.

Bladder exstrophy (BE) is a rare congenital malformation estimated to occur in up to 1/250,000 female live births. The evidence supporting the incidence, uterine preservation and its overall fertility rate in patients with pelvic organ prolapse (POP) and BE is not precisely determined. We report a case of BE and POP in a 27-year-old nulliparous Caucasian. Due to the patient's strong fertility desire, considering her extensive surgical history background, our approach was to correct POP via the Manchester-Fothergill procedure. After 36 months, the patient was still asymptomatic with no evidence for prolapse recurrence. This case demonstrates diagnostic challenges and surgical dilemmas in treatment strategy for patients with BE and co-existent POP. Furthermore, routine long-term surveillance is necessary in terms of renal function, urinary continence, malignancy and possible obstetric issues.

Juvenile cystic adenomyoma mimicking a Mullerian uterine anomaly successfully treated by laparoscopic excision.

A 14­year­old patient diagnosed with a juvenile cystic adenomyoma mimicking a Mullerian uterine anomaly successfully treated by a laparoscopic excision.

Fetal brain magnetic resonance imaging and long-term neurodevelopmental impairment.

OBJECTIVE: To determine the incidence of fetal brain injury by fetal brain magnetic resonance imaging (MRI) in pregnancies complicated with preterm labor (PL), preterm premature rupture of the membranes (PPROM), and intrauterine growth restriction (IUGR), and to compare fetal brain MRI with prenatal surveillance methods, and with immediate and long-term neurodevelopmental outcome. METHODS: Between February 2007 and January 2009, high-risk pregnancies were analyzed by MRI at 1.5 Tesla after 24 weeks of gestation at the Clinical Hospital Center Zagreb, Croatia. Long-term outcome was defined as neurodevelopmental outcome at 24 months. RESULTS: Among 70 pregnancies analyzed, 40.0% had abnormal fetal brain MRI. The highest incidence occurred in the PL group. There was no correlation between abnormal MRI and fetal surveillance methods (ultrasound, Doppler blood flow analysis, cardiotocography, biophysical profile) or immediate neonatal outcome (1-minute Apgar score, umbilical cord pH). Via MRI, fetal brain injury would have been diagnosed for 45.7% of fetuses with a long-term neurodevelopmental handicap. Binary logistic regression showed that, as compared with other surveillance methods, fetal brain MRI was the best predictor of long-term neurodevelopmental disability. CONCLUSION: PL, IUGR, and PPROM were associated with an early intrauterine CNS insult that was not accurately detected by existing prenatal testing options.

Perinatal factors associated with the neurologic impairment of children born preterm.

OBJECTIVE: To determine the perinatal risk factors of long-term neurologic impairment for preterm infants. METHODS: A case-control study was conducted with 60 neurologically impaired and 60 healthy children, all born prematurely. RESULTS: There was no relation between neurologic impairment and maternal pregnancy complications or prenatal steroid administration, bacteriologic content of cervical smear, fetal presentation, fetal heart rate, or mode of delivery. Cerebral palsy was associated with early neurologic signs, perinatal asphyxia, neonatal septicemia, abnormal brain ultrasound findings, prolonged interval between rupture of membranes and delivery, and multiple placental lesions. Children with minimal cerebral dysfunction were more frequently first born. Multiple placental lesions, neonatal septicemia, abnormal brain ultrasound findings, and perinatal asphyxia were independently correlated with long-term neurologic impairment. CONCLUSION: Perinatal infection, perinatal asphyxia, and abnormal brain ultrasound findings seem to be risk factors for cerebral palsy whereas primigravidity seems to be correlated with minimal cerebral dysfunction.

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.

Long-term neurodevelopmental outcome of triplets.

OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in triplets and to find out possible connection between the outcome and perinatal events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24-144 months of age correlated with gestational age, birth weight, pregnancy complications, early neonatal period, neonatal cranial ultrasound, period of birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low birth weight and maternal age. In multivariate analysis, both cerebral palsy and minor disabilities correlate significantly with early neonatal complications, neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture of membranes (p=0.047). Children conceived spontaneously do worse than those born after assisted reproduction (p=0.004), those born in the time period 1996-2000 do better than those born before (p=0.021). Seventy-seven percent (77%) of newborns delivered in the time period 1996-2000 and after level 1 antenatal care was introduced, compared with 54% being delivered in the time period before 1996 and with less meticulous types of antenatal care, remain healthy (p=0.015). CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental complications. Stringent perinatal care might appear important determinant of their long-term outcome.

[Magnetic resonance imaging in fetal medicine]. / Uloga magnetske rezonancije u fetalnoj medicini.

Fast magnetic resonance imaging (MRI) has revolutionized our ability to image the fetus by using fast scanning techniques. Individual images are obtained in 300-400 s allowing fetal imaging without sedation due to reduced fetal movement artifacts. MRI is most useful for evaluation of the anomalies of fetal nervous and urinary system which are not fully clarified by ultrasound. The influence of magnetic resonance depending on gestational age on perinatal management nowadays is certain. This review discusses its current application and future developments.