Gestational diabetes mellitus: Prevention, diagnosis and treatment. A fresh look to a busy corner.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycaemia with onset or first recognition during pregnancy. Risk factors include family history of diabetes, previous GDM, genetic predisposition for GDM/type 2 diabetes, insulin resistance conditions such as overweight, obesity and ethnicity. Women with GDM are at high risk for fetal macrosomia, small for gestational age, neonatal hypoglycaemia, operative delivery and caesarean delivery. The aim of this narrative review is to summarize the most recent findings of diagnosis and treatment of GDM in order to underline the importance to promote adequate prevention of this disease, especially through lifestyle interventions such as diet and physical activity. METHODS: The research was conducted using the following electronic databases, MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library, including all published randomized and non-randomized studies as well as narrative and systematic reviews. RESULTS: The lack of universally accepted criteria makes the definition of diagnosis and prognosis of this condition difficult. Early diagnosis and glucose blood level control may improve maternal and fetal short and long-term outcomes. Treatment strategies include nutritional interventions and exercise. Medical treatment can be necessary if these strategies are not effective. Moreover, novel non-pharmacologic agents such as myo-inositol seem to be effective and safe both in the prevention and the treatment of GDM. CONCLUSIONS: It is important to promote adequate prevention of GDM. Further studies are needed in order to better define the most appropriate strategies for the clinical management of women affected by GDM.

Cystic Fibrosis Mutation Spectrum in North Macedonia: A Step Toward Personalized Therapy.

The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTR gene. The knowledge of CFTR mutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the CFTR gene were analyzed using commercial kits. If the genotype was undetermined, all CFTR exons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the CFTR gene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of CFTR mutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.

Menopause-specific Quality of Life Questionnaire: factor and Rasch analytic approach.

OBJECTIVE: The study aimed to assess the psychometric properties of the Menopause-specific Quality of Life Questionnaire (MENQOL) in Serbian climacteric women. METHODS: Two hundred mid-aged (40-65 years) women filled out a general sociodemographic and medical questionnaire, the MENQOL, the Short Form-36 questionnaire (SF-36), and Beck's Depression Inventory (BDI). The MENQOL was translated according to recommended methodology and its psychometric properties (internal consistency, discriminant, construct and criterion validity, factor and Rasch analyses) were assessed. RESULTS: Cronbach's alpha coefficient for the Serbian MENQOL was 0.957 (Vasomotor =0.917, Psychosocial =0.907, Physical =0.928, Sexual =0.913). Corrected item-total correlation coefficients were >0.50 for all items. Factor analysis extracted six domains with total variance of 72.02%. Beside the four original domains, two new domains were observed: Attractiveness and Pain. Factor loadings for all items were appropriate (>0.4). The MENQOL correlated with the SF-36 and BDI total scores, suggesting good criterion validity. Rasch analysis showed adequate reliability (item =0.91; person =0.79) and separation (item =1.95; person =3.21) indexes, proving good reproducibility and reliability of the Serbian MENQOL. All items had infit and outfit mean squares in the standard accepted range. CONCLUSION: Principal component analysis showed somewhat different constructs from the original scale. However, Rasch analysis confirmed that the MENQOL represents a good metric instrument for menopausal symptoms.

Vagina as a rare location of renal cell carcinoma metastasis.

INTRODUCTION: Metastatic renal cell carcinoma is often found in distant organs, including lung, bone, brain, and liver. Metastases to the vagina are extremely rare. CASE REPORT: The authors present a case of renal cell carcinoma metastasis to the anterior vaginal wall four months after nephrectomy in a 56-year-old patient. The vaginal lesions were excised. After two years the patient had no signs of recurrence or the disease progression. CONCLUSION: Vaginal metastases should be considered in differential diagnosis of female renal cell carcinoma patients presenting with vaginal bleeding of mass.

Sp100A is a tumor suppressor that activates p53-dependent transcription and counteracts E1A/E1B-55K-mediated transformation.

Human adenoviruses (HAdV) are used as a model system to investigate tumorigenic processes in mammalian cells where the viral oncoproteins E1A and E1B-55K are absolutely required for oncogenic transformation, because they simultaneously accelerate cell cycle progression and inhibit tumor suppressor proteins such as p53, although the underlying mechanism is still not understood in detail. In our present study, we provide evidence that E1B-55K binding to the PML-NB component Sp100A apparently has an essential role in regulating adenovirus-mediated transformation processes. Specifically, when this E1B-55K/Sp100A complex recruits p53, Sp100A-induced activation of p53 transcriptional activity is effectively abolished. Hence, Sp100A exhibits tumor-suppressive activity, not only by stabilizing p53 transactivation but also by depressing E1A/E1B-55K-mediated transformation. E1B-55K counteracts this suppressive activity, inducing Sp100A SUMOylation and sequestering the modified cellular factor into the insoluble matrix of the nucleus or into cytoplasmic inclusions. These observations provide novel insights into how E1B-55K modulates cellular determinants to maintain growth-promoting activity during oncogenic processes and lytic infection.

Impact of Conception Method on Twin Pregnancy Course and Outcome.

Objective: The aim of the study was to investigate the course and outcomes of twin pregnancies conceived by different methods of assisted reproduction (ART) compared to those conceived spontaneously. Methods: The study involved patients with twin pregnancies who delivered at the Ob/Gyn Clinic of the Clinical Center of Serbia over a period of three years. Patients were differentiated according to method of conception and type of ART. Age, parity, etiology of infertility, pregnancy complications, time of membrane rupture and type of delivery was recorded for each patient. Gestational week at delivery, presentation, birth weight, Apgar score, chorionicity and accompanying disorders were separately recorded for each twin. The data were analyzed statistically. Results: A total of 431 patients were included in the study. Although more twins were conceived by ART, the difference was not statistically significant (p = 0.092). The most common ART procedure was IVF/ICSI (p = 0.001). ART procedures, particularly IVF/ICSI, were significantly correlated with more advanced maternal age, fewer previous pregnancies and delivery by cesarean sections, usually planned (p = 0.001). Preterm membrane rupture was more common after ICSI, but preterm delivery and pregnancy complications were infrequent, irrespective of the method of conception (p = 0.001). ART twins were mostly dichorionic (p = 0.036). Monochorionic twins were conceived either spontaneously or with ICSI. Conception by ART was not correlated with twins' outcome (weight, Apgar score, disorders). Conclusions: ART procedures do not have a negative impact on twin pregnancy course and outcome. Twin pregnancies conceived spontaneously or by ART have similar outcomes.

GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells.

PURPOSE: Natural products have been investigated for promising new leads in pharmaceutical development. The purpose of this study was to analyze the biological effect of GE132+Natural, a novel supplement consisting of 5 compounds: Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly. METHODS: The antiproliferative activity of GE132+Natural was tested on 3 different human cancer cell lines: MCF7 (breast cancer cells), PC3 (prostate cancer cells), and SW480 (colon cancer cells), as well as on EA.hy 926 (normal human endothelial cell line). In addition, the cytotoxicity of GE132+- Natural on the proliferation of primary human mesenchymal stem cells isolated from dental pulp (DP=MSC), along with its in vitro impact on different peripheral blood parameters, was determined. RESULTS: The results revealed high antiproliferative activity of GE132+Natural on all tested cancer cell lines (PC3, MCF7 and SW480), as well as on the EA.hy 926 endothelial cell line in a dose-dependent manner. However, applied in a wide range of concentrations GE132+Natural did not affect both the proliferation of primary mesenchymal stem cells and the peripheral blood cells counts. CONCLUSION: The data obtained demonstrated that GE132+Natural is effective in inhibiting cancer cell proliferation, indicating its potential beneficial health effects. In addition, the results pointed that adult mesenchymal stem cells might be valuable as a test system for evaluating the toxicity and efficacy of new medicines or chemicals.

Predictive factors of malignancy in patients with adnexal masses.

INTRODUCTION: Good preoperative tumor triage is essential for choosing the appropriate approach. OBJECTIVE: The study aim was to identify factors from standard preoperatively collected data, which could predict the nature of adnexal masses prior surgery. MATERIAL AND METHODS: The study involved all women treated in the Clinic for Gynecology and Obstetrics Clinical Center of Serbia for adnexal tumors throughout a period of 18 months. On admission, detailed anamnestical and laboratory data were obtained and ultrasound scans were performed. Obtained data were compared with hystopathological findings of tumors. Methods of correlation and logistic regression were applied to create association models. RESULTS: Three new models for predicting tumor nature were achieved from anamnestical data, characteristics of women and tumors, and laboratory analyses. Two statistically significant (p = 0.000) equations were obtained for anamnestical data and characteristics of women and tumors, while three were made for laboratory analyses. Sensitivity of anamnestical malignancy index (AMI) was 73.33%, specificity 72.87%, positive predictive value (PPV) 39.49% and negative predictive value (NPV) 91.88%. Sensitivity of characteristic malignancy index (CMI) was 92.38%, specificity 67.36%, PPV 40.59% and NPV 97.34%. Sensitivity of laboratory malignancy index (LMI) was 56.45%, specificity 90.24%, PPV 68.63%, and NPV 84.57%. CONCLUSIONS: The best predictors of malignancy are menopausal status, body mass index (BMI), age, metastases, ascites, tumor marker CEA level, and erythrocyte sedimentation rate (ESR). Along with the risk of malignancy index (RMI), for more reliable triage and preoperative tumor evaluation the authors propose introduction of another three indexes (AMI, CMI, LMI) in clinical practice.

Vaginal Removal of Very Large Nascent Uterine Myoma - Case Report and Literature Review.

This report shows that even extremely large nascent uterine myomas can be removed vaginally. A 25-year-old nulligravid and nulliparous patient with malaise, hypermenorrhea, and intermittent cramping pain in the lower abdomen was referred to our clinic. Gynecological examination revealed a round cauliflower-like tumor, 7 cm in diameter, originating from the external cervical os with a rough surface and without a palpable stalk or base. Ultrasound scan showed a hyperechogenic mass within the uterine cavity with two distinct subunits: one (55 × 44 mm) well-demarcated from the surrounding structures and the other (43 × 38 mm) in close proximity to the lower part of the anterior uterine wall and in continuity with the myometrium. At surgery, the myoma was completely removed vaginally. Recovery was prompt, complete, and uneventful. Follow-up at one and three months confirmed normal gynecological and sonographic findings. In conclusion, vaginal myomectomy is the treatment of choice for prolapsed pedunculated submucous myoma; even extremely large nascent myomas can be efficiently removed vaginally.

Conservative management of massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease--a case report.

Von Willebrand disease (VWD) is the most common inherited bleeding condition that involves extended or excessive bleeding, caused by the deficiency or defect of von Willebrand factor (VWF). Hematoperitoneum as a complication of gynecologic diseases represents acute condition which is usually caused by the hemorrhagic corpus luteum or a rupture of either ectopic pregnancy or a hemorrhagic ovarian cyst. The authors present a unique case of conservatively managed massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease who had right adnexectomy due to hemorrhagic corpus luteum four months prior. This conservative management by blood product and factor concentrate support could be a method of choice in selected hemodynamically stable patients. Furthermore, recurrent bleeding episodes following ovulation could be prevented by suppression of ovulation using oral contraceptive pills.

The absence of the vomer in the first and early second trimester of pregnancy - a new marker of trisomy 21 and trisomy 13.

PURPOSE: The aim of this study was to measure the two frontomaxillo-facial (FMF) angles: the FMF-vomer (FMF-v) and the FMF-palate (FMF-p), and to visualize the vomer in the 1(st) and early 2(nd) trimester, in order to ascertain whether they can be used as markers for trisomy 21 and trisomy 13. MATERIALS AND METHODS: A 2D ultrasound scan was performed in the 340 normal and 12 abnormal pregnancies, using the linear, convex and endovaginal probes. RESULTS: We visualized the FMF angles within 1 to 5 minutes in 253 (72 %) of cases by using the linear probe. FMF-v angle was significantly smaller that the FMF-p angle (79.8° vs. 89.7°, 71.5° vs. 84.5° for the two trimesters, respectively), and that the value of both angles decreased in the second trimester. There was not one single case of trisomy in which vomer could be identified in the 1 (st) and early 2 (nd) trimester. The FMF-p angle failed to present difference between normal cases and the ones with trisomy (89.5°). There was not one single case of trisomy (21 or 13) in which vomer or FMF-v could be identified in the first or early second trimester. The diagnostic accuracy of vomer as a marker for trisomy was 0.985. CONCLUSION: If the vomer cannot be visualized in the 1 (st) and early 2 (nd) trimester, it is important to check the karyotype, and it is not necessary to measure the FMF-p angle. The high resolution probe (L 12 - 5 Mhz) enables easier assessment of the vomer.

Impact of Phytoestrogens on Serum Lipids in Postmenopausal Women.

Objectives: The aim of the study was to assess the impact of soy- and red clover-derived isoflavones on serum lipid levels in postmenopausal women and to compare the effects to the lipid levels of healthy postmenopausal women without phytoestrogen supplementation. Materials and Methods: Blood levels of triglycerides, total cholesterol and cholesterol fractions were assessed. Measurements were performed before treatment and at 6-month intervals over a period of 18 months. The investigation included 74 healthy postmenopausal women randomized into three groups according to treatment. The first group of 23 patients received soy-derived isoflavones, the second group (26 patients) was given red clover-derived phytoestrogens, while the third control group (25 patients) received no supplements. Results: Mean triglyceride, cholesterol and LDL levels of patients in the control group were significantly higher than in both the soy and the red clover groups (p < 0.001) at all three time points, while mean values did not differ significantly between the soy and the red clover groups. The mean HDL levels of patients in the control group was significantly lower than in both the soy and the red clover groups (p < 0.001). Conclusions: Phytoestrogen supplementation had a positive metabolic effect on serum lipid levels in postmenopausal women. The impact on serum lipids levels was similar for soy and red clover.

[A look into the larynx--two centuries along the path of laryngoscopy].

Both the design and purpose of the laryngoscope have been changed significantly since Alfred Kirstein invented his own "laryngeal mirror"--the autoscope. An initially straight, rigid oesophageal tube has been reshaped into a number of laryngeal blade modifications, suitable for use in various patient subpopulations. A tool initially intended to help otorhynolaryngologists diagnose and treat laryngeal diseases has been transformed into an instrument intended to help anesthesiologists intubate the trachea for the purpose of either anesthesia administration or airway maintenance. As direct laryngoscopy depends greatly upon individual manual skills, there has been almost no beginner who feels no proud of his first successful intubation. Thus, we should never forget the pioneers of laryngoscopy whose curiosity, creativity, and enthusiasm enabled us to give a clear and safe look into the larynx.

Synchronous presence of cellular angiofibroma and lipoma in vulvoinguinal region: a unique case report.

A 26-year-old woman presented with a 7-month history of a slowly growing right-sided, well-circumscribed, subcutaneous, soft, painless, large vulvoinguinal lump that now measured up to 12 cm. Adjacent to but separate from this was a well-circumscribed, soft, painless, mobile, large inguinal tumor 8 cm in diameter that had been present unchanged for 2 years. Both lesions were completely excised. Histologically, the first mass was consistent with cellular angiofibroma, whereas the second one had the typical features of lipoma. According to the available literature, this is the first case of synchronous presence of cellular angiofibroma and lipoma in one patient.

Comparison of light and fluorescence microscopy for xylem analysis in tomato pedicels during fruit development.

The xylem hydraulic connection between shoot and fruits has previously been investigated, but contradictory conclusions were drawn about the presence of a flow resistance barrier in the pedicel. In this paper we were studying effect of the drought on the functional xylem vessels in the pedicels of tomato fruit. Commercial tomato genotype was grown in cabinet conditions under two watering regimes (full and deficit irrigation). An aqueous solution of eosin Y were used to visualize the path of water movement through tomato fruit pedicel and fluorescence microscopy observations were done on transversal and longitudinal sections. Dye uptake studies suggested that in well watered plants and in plants exposed to drought, a large majority of xylem vessels are not functional in water transport. Reduced-irrigation treatment significantly altered number and width of functional xylem elements in the fruit pedicel, especially in the abscission zone. This indicates that drought modifies xylem architecture and, thus, environmentally produced change in the hydraulic property of pedicel may affect fruit development.

Immature ovarian teratoma in a young girl: very short course and lethal outcome. A case report.

Immature teratomas of the ovary represent less than 1% of all ovarian teratomas. They contain several tissues that derive from the three embryologic layers: ectoderm, mesoderm, and endoderm. We report the case of a 17-year-old girl who presented with an immature teratoma of the left ovary that recurred 3 months later as an inoperable malignant neuroepithelial peritoneal tumor resembling a glioblastoma. She died 3 weeks after the second explorative operation. The very aggressive course and fast lethal outcome could be explained by the patient's refusal to receive chemotherapy after the initial operation.

Laparoscopic management of consecutive ovarian pregnancy in a patient with infertility.

The diagnosis of ovarian pregnancy is based on the improper rise of serum beta-hCG levels, sonographic findings of an empty uterus, highly characteristic ovarian formation with double hyperechogenic ring surrounding small hypoechogenic field, and the laparoscopic verification of Spiegelberg's criteria. We present a case of ovarian pregnancy in spontaneous cycle in 34-year-old woman following two unsuccessful IVF/ET procedures and ovarian pregnancy on contralateral side laparoscopically treated seven months ago, also achieved in non-stimulated, spontaneous cycle. On admission she had a serum hCG level of 596 mIU/mL on cycle day 46 and an empty uterus. Transvaginal sonography showed a 20 mm ring-like thick-walled hyperechogenic structure within the left ovary. The echogenic ring was surrounded by irregular, hypoechogenic structures suggestive of an ovarian pregnancy with periluteal hemorrhage and blood clots. The ruptured cystic ovarian pregnancy and the corpus luteum were removed by laparoscopy. During the procedure we have seen two clips on the right ovary placed laparoscopically to achieve hemostasis after rupture of the ovarian pregnancy seven months ago. Histopathology showed isolated chorionic villi within hemorrhagic areas in the vicinity of the corpus luteum.