MicroRNA expression as a diagnostic parameter in early endometrial cancer.

OBJECTIVES: MicroRNAs (miRNAs) have emerged as biomarkers that showed strong diagnostic potential in various diseases, including cancer. This study aimed to estimate the expression and diagnostic potential of miRNAs (miR-200a, miR-21, miR-210, miR-126, and miR-130a) in endometrial cancer samples. The DICER1 and AGO2 genes were also analysed. METHODS: The expression of miRNAs, DICER1, and AGO2 was quantified using the quantitative real-time PCR method in 40 tissue samples with early-stage endometrial cancer and 16 normal controls. RESULTS: All tested miRNAs showed significantly higher expression in endometrial cancer compared with the control group, while DICER1 was significantly downregulated. The expression levels of miR-200a, miR-21, and miR-210 were negatively correlated with DICER1 expression. Individually, miR-200a, miR-21, miR-210, and DICER1 showed the best diagnostic performance in distinguishing patients with endometrial cancer from normal controls, whereas a combination of all biomarkers resulted in an even higher area under the curve. CONCLUSIONS: Our study showed that a panel of selected biomarkers (miR-200a, miR-21, miR-210, miR-126, miR-130a, DICER1, and AGO2) may be candidates for the detection of early-stage endometrial cancer.

High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review.

Objective: The aim of this review was to determine whether selective serotonin reuptake inhibitors (SSRIs) affect the ability to conceive in men and women of reproductive age, as well as to find out whether there are certain differencies between them in terms of effects on fertility. Methods: Our review was based on systematic search of literature in four online databases: Medline (PubMed), Scopus, Web of Science and SCIndex (Serbian Citation Index). Results: Several clinical studies reported that SSRIs can decrease the number and viability of sperm, and cause a disruption of their morphological structure. Regarding the effect of these antidepressants on female fertility, some experimental findings suggest that paroxetine and escitalopram may have a negative effect on the ability to conceive due to their stimulatory effect on fallopian tube motility. However, several observational studies favor the use of SSRIs in women with depression/anxiety undergoing in vitro fertilization (IVF) given their efficiency in suppressing these unpleasant symptoms without a relevant negative impact on IVF outcomes. Conclusions: SSRIs should be avoided male patients of reproductive age who wish to conceive, while the use of these antidepressants seems to be justified in women with depression or anxiety who have undergone IVF.Key pointsSSRIs could cause dose and duration-dependent reversible adverse effects on male fertility parameters.In depressed or anxious male patients of reproductive age who wish to conceive mirtazapine or bupropion should be used because of their lower potential to cause sexual side effects.The results of certain experimental studies indicate that paroxetine and escitalopram may have a negative effect on the fertility of female patients.The use of SSRIs in women with depression or anxiety who have undergone IVF seems to be justified, because these psychiatric disorders reduce the likelihood of becoming pregnant.

Assessment of Chromosomal Damage in Umbilical Blood Lymphocytes of Newborns from Kragujevac in Central Serbia Born 18 Years after Environmental Contamination.

The measurement of micronuclei (MN) in umbilical blood lymphocytes of newborns are increasingly used in cytogenetic epidemiology as one of the preferred methods for assessing chromosomal damage resulted from maternal exposure to mutagen. In the present study, we evaluated the effect of strong environmental contamination (EC) (which occured in the City of Kragujevac, Central Serbia in 1999) on the MN frequency in group of 22 newborns born in Kragujevac 18 years after EC, using cytokinesis-block micronucleus (CBMN) assay. The mean MN frequency in umbilical lymphocytes of these newborns was 5.14 ± 2.17/1,000 binucleated (BN) cells, which is significantly lower than mean MN frequency of newborns born 12 months after contamination (9.36 ± 5.60/1,000 BN cells). Sex of newborns, age of mothers, cigarette smoking, and number of pregnancies did not affect the MN frequency of newborns. Our results showed that in utero exposure to environmental pollution affected genome instability of the fetuses, but that by improving the quality of environmental conditions there was a decrease in mean MN frequency of newborns born 18 years after contamination. In general, genome of umbilical lymphocytes shows a realistic picture of all changes in body and the environment.

Antimicrobial treatment in invasive infections caused by Gordonia bronchialis: systematic review.

Background: Corynebacterium, Nocardia, Rhodococcus, Mycobacterium, as well as Gordonia genera belongs to the genus Gordonia, Actinomycetia class. Gordonia bronchialis is a nitrate-reducing, urease-producing, non-motile, force aerobe with a rod-like figure that is known to arrangement into sessile, cord-like groups. This systematic review aimed to establish whether and what invasive infections in humans were caused by Gordonia bronchialis, and to evaluate outcomes of administered antibiotic treatment. Methods: We have registered this systematic review in PROSPERO database of systematic reviews and meta-analyses with the number CRD42022369974. Results: A total of 24 publications were included (22 case reports and two case series) with 28 individual cases. The oldest patients had 92 years, and the youngest patients had 13 years. Clinical signs of infection were present in six patients (21%). All isolates were susceptible to ciprofloxacin, imipenem, and amikacin. Vancomycin was the most frequently used antibiotic with nine cases followed by ciprofloxacin, ceftriaxone, and amoxicillin/clavulanic acid. Conclusion: Although there are no standardized recommendations to date, successful treatment with a favorable outcome has most often been carried out with fluoroquinolones, vancomycin with or without aminoglycosides, as well as carbapenems.

Computer simulation of cervical tissue response to a hydraulic dilator device.

BACKGROUND: Classical mechanical dilators for cervical dilation are associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. A new medical device called continuous controllable balloon dilator (CCBD) was constructed to make a significant reduction in all of the side effects of traditional mechanical dilation. METHOD: In this study we investigated numerically the cervical canal tissue response for Hegar and CCBD using our poroelastic finite element model and in-house software development. Boundary conditions for pressure loading on the tissue for both dilators in vivo were measured experimentally. Material properties of the cervical tissue were fitted with experimental in vivo data of pressure and fluid volume or balloon size. RESULTS: Obtained results for effective stresses inside the cervical tissue clearly showed higher stresses for Hegar dilator during dilation in comparison with our CCBD. CONCLUSION: This study opens a new avenue for the implementation of CCBD device instead of mechanical dilators to prevent cervical injury during cervical dilation.

Testing of new instrument for measuring quality and diversity of nutrition in pregnancy.

OBJECTIVES: Our aim was construction and development of a new questionnaire for assessing the quality and diversity of nutrition of pregnant women. MATERIAL AND METHODS: This was a cross-sectional study. The novel questionnaire was developed through eight steps according with internationally accepted guidelines for questionnaire development. The questionnaire with 18 questions and answers according to the Likert's scale was created and called Balkan Food Quality and Diversity in Pregnancy Questionnaire-18 (BFQDPQ-18). Reliability testing and factor analysis of BFQDPQ-18 were carried out on a sample of 382 women in the third trimester of pregnancy whose pregnancy control and monitoring were performed at the Clinic for Gynecology and Obstetrics of the Clinical Center in Kragujevac, Serbia. RESULTS: The first test of reliability indicated high levels of internal consistency, with the Cronbach's alpha of 0.85 of the BFQDPQ-18. After dividing the BFQDPQ-18 into two parts of nine questions each by split-half method, the Cronbach's alphas were 0.799 and 0.716. The Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO) was 0.878, and the Bartlett's test of sphericity: 1,892.206, p < 0.000. Factor analysis revealed four factors explained in total 51.99% of the variance: mean meal and snack, foods with a low degree of industrial processing, subjective assessment of dietary quality and starchy foods. CONCLUSIONS: The final version of the BFQDPQ-18 showed high reliability and good psychometric properties, so we believe it could be useful instrument for assessing the quality of nutrition of pregnant women.

The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives.

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women's reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium-glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.

Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units.

Intensive care units (ICUs) are expert hospital areas that provide treatment and 24 h care for people who are very sick. Sepsis represents a serious, severe condition and it can lead to septic shock and multiple organ dysfunction syndromes and is one of the most common reasons for patients' hospitalization in ICUs. We wanted to explore the prognostic values of interleukin (IL) 33, soluble suppression of tumorigenicity 2 (sST2), IL 27, and galectin 3 in critically-ill patients. We assumed that these parameters in combination or alone could predict mortality in ICU patients. This research represents a clinical non-randomized prospective study, performed at the Medical Military Academy, a tertiary care hospital in Belgrade, Serbia. The patients were divided in four groups: patients with sepsis (peritonitis, pancreatitis, trauma) and patients without sepsis (trauma). Total number of patients enrolled in the study was 151 and average years of patients were 56.48. The values greater than the cut-off were the predictors of mortality. The IL-33, IL-27 as well as galectin-3 can successfully predict the outcome of critically-ill patients in ICUs. The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs.

Factors associated with fetal growth restriction and small for gestational age newborns.

OBJECTIVES: To identify risk factors that contribute to the occurrence of fetal growth restriction (FGR) and small for gestational age (SGA) and quantify the strength of their impact. MATERIAL AND METHODS: This study was designed as a retrospective-prospective observational cohort study conducted on pregnant women at the Clinic for Gynecology and Obstetrics at the University Clinical Centre Kragujevac, Serbia. We measured the intrauterine degree of fetal development through the estimated fetal weight (EFW) on ultrasound examination, which was calculated using Hadlock's formula 3. Fetuses whose EFW was below the 10th percentile on the World Health Organization (WHO) fetal growth charts adjusted for gender and gestational age were classified as FGR fetuses, while newborns weighing less than the 10th percentile were considered SGA. RESULTS: The study included 320 pregnant women with an average age of 30.3 ± 5.5 years who gave birth to 332 newborns. The results of univariate and multivariate stepwise backward conditional binary logistic regression showed that the occurrence of FGR during the second trimester was more likely in pregnant women with lower body height and proteinuria. The risk factors for the occurrence of FGR during the third trimester were lower body height and proteinuria, while iron supplementation had a protective effect. SGA newborns were more common in pregnant women who were shorter, had proteinuria, used corticosteroids, or smoked during pregnancy. CONCLUSIONS: Clinicians should pay special attention to pregnant women with lower body height, proteinuria, who smoke and use corticosteroids in order to prevent FGR and SGA.

Analysis of cervical resistance during continuous controllable balloon dilatation: controlled clinical and experimental study.

BACKGROUND: Hydraulic dilatation is a novel method of cervical dilatation that is based on continuous controllable dilatation (CCBD) by the pumping of fluid into the balloon extension of the system. The main advantage of this procedure is that it allows control of and insight into the process of cervical dilatation. METHODS: For the purposes of our research, we created a new and upgraded system for CCBD which consists of a programmed hydrostatic pump connected to a balloon extension. With regard to our aim to precisely measure and determine the location of the cervical resistance, we placed two pressure-measuring films, one on the top and one on the bottom of the balloon extension. This study included 42 patients in whom cervical resistance was measured before suction curettage. RESULTS: Cervical dilatation and measurement of cervical resistance were successful in all patients. The analysis of the pressure-measuring films showed that the points of highest resistance were located in the zone of the internal cervical os and that these values were much higher than those in the zone of the external cervical os (0.402 versus 0.264 MPa at the upper pressure-sensitive film; 0.387 versus 0.243 MPa at the lower pressure-sensitive film). This study also showed that an increase in cervical resistance in the zone of the internal cervical os was followed by an increase in cervical resistance in the zone of the external cervical os. CONCLUSIONS: During CCBD, the internal cervical os is the centre of cervical resistance, and the values do not decline with the number of miscarriages or the number of previous births. TRIAL REGISTRATION NUMBER: ISRCTN Registry identifier: ISRCTN30949871 . Date of registration: 13 May 2015.

Gestational choriocarcinoma of the cervix.

Choriocarcinoma is the most aggressive, malignant form of gestational trophoblastic disease and has varying incidence, increasing in patients older than 40 years. It usually develops after a malignant alteration in a molar pregnancy, but rarely after an abortion or normal or ectopic pregnancies. The most common localization is the uterus, but it can also be found rarely in the ovaries, fallopian tubes, vagina, vulva, cervix or pelvic region. A 38-year-old multiparous woman, with no complications in three previous labors and four miscarriages, presented to her gynecologist one year after the last miscarriage complaining of abnormal vaginal bleeding. Clinical examinations showed normal ultrasound and histopathology findings. Blood analysis demonstrated moderate anemia and low elevated serum b-human chorionic gonadotropin. Due to profuse hemorrhage and anemia after the curettage, the medical council decided that a total hysterectomy should be performed. Macroscopic examination of the post-operative material showed regular morphology of the uterus, fallopian tubes and ovaries. However, a whitish brown lesion with a maximum diameter of 22 mm was noted in a longitudinal section of the cervix. Using standard histopathology and immunohistochemical analysis, a cervical gestational choriocarcinoma was diagnosed. Knowledge of the characteristics of the choriocarcinoma is very important for accurate diagnosis and treatment, especially when the tumor is localized on the rare locations and where a high level of serum b-human chorionic gonadotropin is absent.

Prognostic significance of co-overexpression of bcl-2 and c-erbB-2/neu in uterine cervix carcinomas and premalignant lesions.

AIM: To establish the role of co-overexpression of bcl-2 and cerbB- 2/neu protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, cervical carcinoma in situ and cervical invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). METHODS: The expression of bcl-2 and c-erbB-2/neu was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (p less than 0.05) was used to assess statistical significance. RESULTS: Co-overexpression of Bcl-2 and c-erbB-2/neu was found to increase in direct relation to the grade of the squamose intraepitelial lesions (SIL) of cervix. Statistically significant difference was found in the frequency of co-overexpression in patients with high grade SIL (12/22, p=0.006), cervical carcinoma in situ (10/22, p=0.018) and cervical invasive carcinoma (12/26, p=0.012), in relation to the control group. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. CONCLUSION: On the basis of high predictive values it can be said that in patients with co-overexpression of bcl-2 and c-erbB-2/neu overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of these oncogenes in cervical carcinogenesis.