Transvaginal sonographic evaluation at different menstrual cycle phases in diagnosis of uterine lesions

Masomeh Hajishaiha1, Mohammad Ghasemi-rad2, Nazila Karimpour1, Nikol Mladkova3, Farzaneh Boromand11Department of Gynecology, 2Student Research Committee (SRC), Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran; 3Institute of Cell and Molecular Science, London, UKPurpose: Intrauterine lesions (IULs) are a common finding in women of reproductive age, particularly infertile women. Transvaginal sonography (TVS) is a popular tool for IUL detection, but there are conflicting data with respect to its accuracy.Methods: Five hundred and six women were enrolled into the study. Of these, 496 underwent hysterosalpingography and subsequent TVS six different times during the course of their menstrual cycle. If a lesion was detected, it was further evaluated by sonohysterography (SHG) and hysteroscopy.Results: Of 496 women, 41 were shown to have IULs by TVS and those lesions were confirmed in 39 by SHG and hysteroscopy. All 39 lesions were detectable during the ovulatory and early luteal phase (days 16–19) of the menstrual cycle. Accuracy of TVS during different phases was largely dependent on the size of the lesion. TVS falsely detected two lesions and missed fine adhesions in two patients.Conclusion: Accuracy of TVS in detection of IULs is highly dependent on the menstrual cycle phase, with the ovulatory and early luteal phase being the optimal time for this examination.Keywords: menstrual cycle phase, space occupying lesions, transvaginal sonograph

Role of iron supplementation in promoting maternal and fetal outcome

Zahra Yekta1, Reza Pourali2, Nikol Mladkova3, Mohammad Ghasemi-rad4, Farzane Boromand5, Khosrow Hazrati Tappeh6 1Department of Community Medicine; 2Medical Demonstration Facility, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran; 3Institute of Cell and Molecular Science, London, United Kingdom; 4Student Research Committee; 5Department of Obstetrics and Gynecology; 6Department of Mycology and Parasitology, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran Background: The data comparing daily versus intermittent iron supplementation during pregnancy remain controversial. This study was undertaken to compare the efficacy of daily versus two different intermittent iron supplementation regimes on hematologic markers and birth outcomes in nonanemic pregnant women. Methods: Two hundred and ten women with singleton pregnancies, no known disease, and hemoglobin levels >11.0 g/dL were randomly assigned to one of three groups, ie, Group A consuming two iron supplementation tablets once weekly (100 mg iron per week, n = 70), Group B consuming one tablet twice weekly (100 mg iron per week, n = 70) and Group C, consuming one tablet daily (50 mg iron per day, n = 70). No additional micronutrients were supplied. Hemoglobin and serum ferritin levels were measured at 20, 28, and 38 weeks. Pregnancy and birth outcomes (pregnancy termination, method of delivery, birth weight, stillbirth) were analyzed. Results: In total, 201 women completed the protocol. There was a significant difference in mean hemoglobin and ferritin levels in Group B at 38 weeks (P = 0.018 and P = 0.035, respectively) but this difference was not clinically significant (hemoglobin >12 g/dL, ferritin >19 µg/L). There was a significant increase in ferritin in Group C (P = 0.03) at 28 weeks. No significant difference was observed with respect to pregnancy or birth outcome across the groups. All regimens prevented the occurrence of hemoglobin <10.5 g/dL, but weekly supplementation was associated with development of a hemoglobin level <11.0 g/dL (risk ratio 0.044). Conclusion: Twice-weekly supplementation is as effective as daily supplementation, and may represent an acceptable compromise in iron supplementation regimens for nonanemic pregnant women. Keywords: iron supplementation, pregnancy, anemia, outcom

Glioblastoma-derived spheroid cultures as an experimental model for analysis of EGFR anomalies

Glioblastoma cell cultures in vitro are frequently used for investigations on the biology of tumors or new therapeutic approaches. Recent reports have emphasized the importance of cell culture type for maintenance of tumor original features. Nevertheless, the ability of GBM cells to preserve EGFR overdosage in vitro remains controversial. Our experimental approach was based on quantitative analysis of EGFR gene dosage in vitro both at DNA and mRNA level. Real-time PCR data were verified with a FISH method allowing for a distinction between EGFR amplification and polysomy 7. We demonstrated that EGFR amplification accompanied by EGFRwt overexpression was maintained in spheroids, but these phenomena were gradually lost in adherent culture. We noticed a rapid decrease of EGFR overdosage already at the initial stage of cell culture establishment. In contrast to EGFR amplification, the maintenance of polysomy 7 resulted in EGFR locus gain and stabilization even in long-term adherent culture in serum presence. Surprisingly, the EGFRwt expression pattern did not reflect the latter phenomenon and we observed no overexpression of the tested gene. Moreover, quantitative analysis demonstrated that expression of the truncated variant of receptor—EGFRvIII was preserved in GBM-derived spheroids at a level comparable to the initial tumor tissue. Our findings are especially important in the light of research using glioblastoma culture as the experimental model for testing novel EGFR-targeted therapeutics in vitro, with special emphasis on the most common mutated form of receptor—EGFRvIII

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling

We would like to thank Cancer Research UK, the European Research Council, the British Skin Foundation and Barts and the London Charitable Trust for fundin

Inducible ROCK 2 activation increases primary keratinocyte differentiation but co-operates with ras^Ha activation in transgenic mouse skin carcinogenesis

To investigate ROCK 2 signalling in epidermal differentiation and co-operation with rasHa activation in squamous cell carcinogenesis [SCCs], transgenic mice expressing a conditionally active, 4-hydroxytamoxifen (4HT)-regulated, human ROCK2 transgene from a keratin 14 promoter K14.ROCK<sup>er</sup> were crossed with mice expressing activated ras<sup>Ha</sup> exclusively in epidermal transit amplifying keratinocytes [HK1.ras]. 4HT-treatment of K14.ROCK<sup>er</sup> alone for 12 weeks induced epidermal and follicular hyperplasia but no papillomas. Western analysis of primary K14.ROCK<sup>er</sup>keratinocyte differentiation showed elevated K1 expression following calcium challenge in vitro, consistent with a role in differentiation, whereas little K6 expression was detectable in 4-HT treated K14.ROCK<sup>er</sup> hyperplasia in vivo, an unusual result for epidermal hyperplasia. In addition hyperplastic anagen follicles expressed elevated collagen deposits in the hair bulb/IRS regions, a result also observed in bi-genic K14.ROCK<sup>er</sup>/HK1.ras papillomas. Here, 4-HT treatment for 12-14 weeks had little apparent effect on HK1.ras papillomatogenesis, with tumours appearing by approx 8-10 wks in treated and untreated cohorts. However K14.ROCK<sup>er</sup>/HK1.ras histotype was quite different, with increased collagen deposits appearing in the connective tissue of papillomas, which now expressed K6 but at lower levels and in an atypical, supra-basal fashion compared to untreated, bi-genic controls. Further, the basal layer architecture was also disturbed whilst 4-HT treated K14.ROCK<sup>er</sup>/HK1.ras papillomas taken at 12-14 weeks displayed areas of malignant conversion with both carcinoma in situ and overt SCC. These interesting data demonstrate significant roles for ROCK 2 in epidermal differentiation and identify unique epidermal responses to its deregulated signalling and novel early-stage co-operation with HK1.ras in skin carcinogenesis