Meconium Proteins Involved in Iron Metabolism.

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL (p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment.

The Impact of Platelet-Rich Plasma Application during Cesarean Section on Wound Healing and Postoperative Pain: A Single-Blind Placebo-Controlled Intervention Study.

Background/Objectives: The aim of this study was to evaluate if platelet-rich plasma (PRP) application into the wound during cesarean delivery improves wound healing and reduces pain in the postoperative period. Materials and Methods: A total of 46 patients undergoing cesarean section (CS) were included in this single-blind placebo-controlled intervention study: 23 women in the PRP group and 23 in the placebo group. Every patient was asked to evaluate pain by using the Visual Analogue Scale (VAS) immediately after surgery, as well as 6 and 12 h after the surgery. The use of analgetics was also recorded. The postoperative scar was assessed using the Patient and Observer Scar Assessment Scale (POSAS). Results: There was no case of wound dehiscence in either group. Significant differences between the groups in the scar quality assessment were detected in both patient and doctor POSAS results on days 8, 30 and 90 after surgery in the favor of the PRP group. There was no difference in the pain intensity assessment on the VAS recorded after surgery, but PRP patients required fewer paracetamol doses per day than the control group. Conclusions: PRP application during CS significantly improved wound healing in both short- and long-term assessment. Although it did not influence postoperative pain intensity, it may reduce the use of analgetics after surgery.

sFlT-1/PlGF ratio as a predictor of preeclampsia in COVID-19 pregnant patients.

The association between SARS-CoV-2 infection in pregnancy and preeclampsia is widely debated in numerous studies. The aim of our study was to investigate whether an increased sFlt-1/PlGF ratio is a good marker of preeclampsia in pregnant patients with COVID-19 infection. This single centre prospective study was conducted in the Department of Obstetrics and Gynaecology, at the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw. The study group consisted of 68 COVID-19 pregnant patients and 57 SARS-CoV-2 negative pregnant controls. Serum sFlt-1/PlGF ratio was assessed. The two groups did not differ in terms of the frequency of IVF, nulliparity, history of hypertension, pre-gestational diabetes and chronic kidney disease. The primary outcome was the diagnosis of preeclampsia. Preeclampsia was diagnosed in 10 patients in both groups. The sFlt-1/PlGF ratio higher than 38, considered highly suggestive of developing preeclampsia, was found in 20 patients in the COVID-19 group and 15 patients in the control group. The odds of developing preeclampsia in patients with sFlt-1/PlGF ratio > 38 was approximately 4-fold higher in COVID-19 group and 11-fold higher in controls. Sflt-1/PlGF ratio does not differ significantly between the SARS-CoV-2-positive and SARS-COV-2-negative pregnant patients. The sFlt-1/PlGF ratio > 38 is associated with higher odds of the diagnosis of preeclampsia in both of these groups, and therefore may serve as its marker regardless of COVID-19 infection status.

Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Rhabdomyosarcoma of the genitourinary system in girls - the role of magnetic resonance imagining in diagnosis, treatment monitoring, and follow-up.

OBJECTIVES: Rhabdomyosarcoma of the genitourinary system in girls is a rare neoplasm, especially in non-dedicated centers. Our work aimed to sum up and present genitourinary rhabdomyosarcomas in girls from the radiological point of view. MATERIAL AND METHODS: We retrospectively reviewed all girls with genitourinary RMS who underwent treatment at the Institute of Mother and Child in Warsaw between 2009 and 2022. We evaluated the demographic, clinical, and pathological patient data and imaging studies. RESULTS: During the study period, ten patients presented with genitourinary RMS and underwent magnetic resonance imaging (MRI). The median age at the time of diagnosis was 2.8 years, six patients were younger than three years, and four patients were older than ten years. The most common clinical symptoms were tumor fragments protruding from the vagina/falling out of the vagina and vaginal bleeding or discharge, and the most common original location was the vagina. One hundred percent of patients had the embryonal subtype of RMS, and 100% of cases where molecular tests for PAX3/FOXO1 fusion gen status were performed had negative status. At presentation, the median tumor volume was 114 cm³. Eight patients (80%) were classified as clinical group III according to the IRS Group, and most patients (70%) were in a standard-risk group. All patients received multimodal treatment, including surgery and chemotherapy; 60% received radiotherapy. Neoadjuvant chemotherapy was the primary treatment for all our patients. In six patients (60%) with a measurable tumor mass after a biopsy, a gradual tumor volume reduction was observed after induction chemotherapy (approximately ten weeks of treatment) - all of which had a partial response (PR). All our patients (100%) responded completely to treatment. CONCLUSIONS: MRI was performed at every stage of diagnosis and treatment as well as during follow-up. It allowed for staging, monitoring of chemotherapy, and guided surgery.

Prenatal and Neonatal Ultrasound and Magnetic Resonance Imaging Diagnosis of Sprengel's Deformity with Unusual Associations.

INTRODUCTION: Sprengel's deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and abnormal shoulder function. Nonsurgical management can be considered for mild cases. Surgical intervention is indicated in moderate to severe cases with the goal of improving cosmetic appearance and function. The best surgical results are obtained in children aged 3-8 years. Correct diagnosis is very important because Sprengel's deformity can be accompanied by additional abnormalities, even in mild cases, and lack of a diagnosis delays proper treatment of the child. The severity of the defect may progress, so it is important to correctly identify children with Sprengel's deformity, even those with a mild form of the defect. CASE PRESENTATION: We report a case of prenatal sonographic diagnosis of Sprengel's deformity with additional features, as yet undescribed and missed - although visible - on prenatal magnetic resonance imaging (MRI). Cesarean delivery was performed due to preterm rupture of membranes, and a postnatal MRI confirmed the unusual constellation of Sprengel's anomaly with lateral meningocele, vestigial posterior meningocele, and lipoma tethering of the cord to the dural sac at the cervical-thoracic junction. CONCLUSION: Diagnosis of Sprengel's deformity is possible with prenatal ultrasound. Asymmetry of the cervical spine, discontinuity of the vertebral arch and abnormal vertebral bodies, as well as the asymmetric position of the shoulder blades with the presence of an omovertebral bone are signs that can help diagnose the defect.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy.

Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. It is estimated that it affects 10% of women of reproductive age. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. It is associated with a significant deterioration in quality of life as a result of chronic pelvic pain and may also lead to infertility. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. This review takes into account aspects of the molecular mechanisms involved in the pathophysiology of endometriosis and EP, with particular emphasis on the similarities between them.

The use of super-selective uterine artery branch embolization and methotrexate in cervical pregnancy - case reports and literature review.

Cervical ectopic pregnancy (CEP) is one of the rarest types of ectopic pregnancy. Early detection of such cases increases the chances of conservative treatment and fertility preservation. Within 6 weeks of each other, 2 women were admitted to the OB/GYN Department with cervical ectopic pregnancies. They were successfully treated with a double dose of methotrexate and super-selective uterine artery branch embolization (SUABE). Taking into account health and economic considerations, for instance the optimal recovery time, and lower costs of operating theater time, laboratory testing and outpatient observation, it seems that safe, minimally invasive, fertility-saving, effective systemic administration of MTX in combination with SUABE, can be a rational alternative to cervical ectopic pregnancy treatment.

No COVID-19 Cases Detected Between April and September 2020 After Screening All 838 Admissions to a Maternity Unit in Poland.

BACKGROUND Between April and September 2020, there were <10 000 reported cases of COVID-19 in the Masovia district, Poland, and <1000 new cases daily in Poland. During this period, all new hospital admissions to a maternity unit of a teaching hospital in Warsaw were screened for the COVID-19 infection. This retrospective study presents the findings from the reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. MATERIAL AND METHODS This study included 838 women admitted for delivery between April 20 and September 20, 2020. All the admitted women were assigned to a low-risk or a high-risk group for COVID-19 and underwent RT-PCR nasopharyngeal swab tests (GeneFinder™-COVID-19-Plus-RealAmpKit. OSANG Healthcare Co., Ltd., Gyeonggi-do, Korea) for COVID-19. The testing protocol included repeated testing in case of inconclusive results or negative results in the symptomatic patients. The maternal and neonatal data from these cases were collected and analyzed. RESULTS All of the 838 women tested negative for COVID-19. Two women (0.24%) were classified as high risk for COVID-19. For 4 (0.48%) women, the results were initially inconclusive and negative when repeated. One hundred and eighty-one (21.5%) women presented with comorbidities, and 60 (7.2%) women were ≥40 years old. CONCLUSIONS The findings from this study show that between April and September 2020, there were no cases of COVID-19 infections at the maternity unit of a teaching hospital in Warsaw, Poland. However, the infection rates for COVID-19 across Europe continue to change. Testing protocols have been developed and established for all hospital admissions and it is anticipated that testing methods will become more rapid and accurate.

Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).

OBJECTIVES: To evaluate the effects of a combined Myo-inositol (MI) and D-chiro-inositol (DCI) therapy on the hormonal and metabolic parameters of women with PCOS. Prospective clinical study. Clinical Study registration number - EUPAS25705 Material and methods: Seventy women diagnosed with PCOS according to the Rotterdam criteria were enrolled in this study. Patients received a combined therapy of one tablet that contained 550 mg of inositol (myo-inositol (MI) and D-chiro-inositol (DCI) in a ratio of 10:1) twice a day for 6 months. At each of 3 visits, the body weight, height and BMI were all recorded; and serum levels of free testosterone (fT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and glucose with insulin during standard OGTT (75 g) were measured. Also at each visit, transvaginal ultrasonography and skin condition assessments were performed. RESULTS: Significant body weight reduction and decreases in fT, FSH, LH and insulin levels, as well as significant increase of serum SHBG concentrations were observed. Serum glucose levels during OGTT decreased after 6 months of treatment. Also, skin conditions improved after only three months of treatment. CONCLUSIONS: Combination of MI and DCI in a ratio 10:1 seems to be efficient in improving both metabolic and hormonal parameters in patients with PCOS.

Cumulative summation test for learning curve (LC-CUSUM) in outpatient hysteroscopy.

OBJECTIVES: Outpatient hysteroscopy has become an integral part of postgraduate training in gynecology. It is an operator-dependent procedure, however there are no recommendations regarding total number of performed procedures to reach proficiency. MATERIAL AND METHODS: This study aimed to assess the learning curve (LC) using cumulative summation test for learning curve (LC-CUSUM). RESULTS: A success rate of 97% a failure rate ≥ 10% were established to denote an adequate and an inadequate performance. A third-year trainee needed 56 procedures to reach the predefined level of performance. CONCLUSIONS: As the length of the LC for outpatient hysteroscopy seems highly variable, it is reasonable to provide tailored monitoring while training.

[Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) risk]. / Zespól policystycznych jajników (PCOS), a ryzyko wystepowania cukrzycy ciaziowej (GDM).

Gestational diabetes mellitus (GDM) is a common complication of pregnancy In the course of pregnancy elevated levels of hormones and other proteins having insulin-antagonistic effects lead to higher insulin resistance in peripheral tissues, followed by hyperinsulinemia. Risk factors for the development of GDM have been well-established. However, the debate whether polycystic ovary syndrome (PCOS) may predispose to GDM continues. Patients with PCOS are often affected by obesity dyslipidemia, hyperinsulinemia, and tissue-specific insulin resistance. Obesity occurs in 50% of the cases, while tissue-specific insulin resistance is observed in 20-40% of the affected patients. This paper aims at systematizing risk factors that could contribute to the development of GDM, as well as reviewing literature reports and analyses on the occurrence of a potential correlation.

A randomized, single blind, placebo-controlled trial for the pain reduction during the outpatient hysteroscopy after ketoprofen or intravaginal misoprostol.

STUDY OBJECTIVE: To assess the efficacy of ketoprofen vs intravaginal misoprostol for pain relief during outpatient hysteroscopy. DESIGN: Prospective, randomized, single-blind, placebo-controlled clinical trial (Canadian Task Force classification I). SETTING: Tertiary medical center. PATIENTS: One hundred fifty women referred for hysteroscopy between January and October 2013. INTERVENTIONS: Women were randomized to receive vaginal misoprostol, 400 µg, with 100 mL of 5% intravenous glucose (misoprostol arm); intravenous ketoprofen, 50 mg/mL, in 100 mL 5% glucose with intravaginal placebo (ketoprofen arm); or vaginal placebo tablets, 100 mL 5% intravenous glucose (placebo arm) before outpatient hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A visual analog scale (VAS) was used for 1-dimensional pain assessment. Patients were asked to mark a VAS score before, during, and at 5 and 15 minutes after the procedure. Median VAS scores during and directly after the anesthesia-free hysteroscopy were significantly lower in the misoprostol group than in the ketoprofen (p = .02) or placebo (p = .006) groups. There were no statistical differences between the 3 arms in median VAS score assessed at 15 minutes after the procedure (p = .16). There were no differences in procedure time between groups (p = .16). CONCLUSION: When administrated 4 hours before the procedure, 400 µg vaginal misoprostol seems to reduce the pain during and immediately after hysteroscopy. The effect does not depend on patient age, hormone status, parity, or type of outpatient hysteroscopy (operative or diagnostic).

Synthesis of novel, peptidic kinase inhibitors with cytostatic/cytotoxic activity.

The utility of a novel, chemoenzymatic procedure for the stereocontrolled synthesis of small peptides is presented in the preparation and structure optimisation of dipeptides with cytostatic/cytotoxic activity. The method uses Passerini multicomponent reaction for the preparation of racemic scaffold which is then enantioselectively hydrolysed by hydrolytic enzymes. Products of these transformations are further functionalised towards title compounds. Both activity and selectivity towards tumor cells is optimised. Final compound is shown to be an inhibitor of the protein kinase signaling pathway.

Rare case of uterine PEC-oma (perivascular epithelioid cell tumor) recurrence. Case report and literature review.

Perivascular epithelioid cell tumor (PEC-oma) is a rare mesenchymal neoplasm. Literature reports more than 100 cases of PEC-oma, a third of which is of uterine or uterine retroperitoneum origin. The case of a 59-year-old woman presented here is, to the best of our knowledge, the first described fast uterine PEC-oma recurrence of the tumor of the gastrointestinal tract origin. In this text the authors also present literature review concerning this rare female tumor

Statins impair glucose uptake in tumor cells.

Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered (18)F-fluorodeoxyglucose ((18)F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting (18)F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.

Antitumor effects of the combination of cholesterol reducing drugs.

There are a number of potential mechanisms linking cholesterol homeostasis to processes that are tightly linked with carcinogenesis. Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), the rate-limiting enzyme in the mevalonic acid synthesis pathway, exert cytostatic and cytotoxic effects towards tumor cells. It seems that the cytostatic and cytotoxic effects of statins result from blocking protein prenylation, leading to inhibition of isoprenoid compound synthesis. Another compound which affects cholesterol metabolism is the plant alkaloid berberine. The aim of this study was to investigate potential antitumor effects of lovastatin combined with berberine. Combined with berberine, lovastatin appeared to exert potentiated cytostatic and/or cytotoxic effects against human MDA-MB231 breast cancer and murine Panc 02 pancreatic cancer cells. The obtained results indicated that the effect of berberine is not dependent on blocking protein prenylation in cells, and the toxic effect of lovastatin combined with berberine is reversed by addition of the substrates of this pathway to the level brought out by lovastatin alone. Lovastatin-berberine combination caused cell cycle inhibition in G1 phase after 48 h of incubation with drugs. In a Panc 02 pancreatic cancer model in mice, lovastatin-berberine combination slightly, but significantly, slowed down tumor growth. Taking into account the number of patients treated with the investigated drugs one may suppose that the described interactions may be of clinical value.