Clinical significance of endometrial abnormalities: an observational study on 1020 women undergoing hysteroscopic surgery

Background: The overall clinical significance of the finding of endometrial abnormalities in predicting premalignant/malignant endometrial lesions is still incompletely determined. For this reason the management, surgical or expectant, of women in which an endometrial abnormality has been detected is debated. Methods: This retrospective study was carried out on 1020 consecutive women, 403 premenopausal and 617 postmenopausal, who underwent operative hysteroscopy in a University Hospital for suspected endometrial abnormalities, which were detected by transvaginal ultrasound (TVS) and/or office hysteroscopy. In these women, the clinical characteristics and findings at TVS and hysteroscopy were evaluated in relation to the presence/absence of premalignant/malignant endometrial lesions at pathology report. Results: The clinical characteristics considered were significantly different when the study women were compared according to their menopausal status. Premalignant/malignant lesions were found in 34/1020 (3.33%) women. Complex hyperplasia with atypia and endometrial cancer were detected in 22 (2.15%) and 12 (1.17%) cases, respectively. The postmenopausal women had a significantly higher risk of premalignant/malignant lesions than premenopausal women (O.R. = 5.098 [95% C.I.: 1.782–14.582], P < 0.005). This risk was even higher when abnormal uterine bleeding (AUB) was present (O.R. = 5.20 [95% C.I.: 2.38–11.35], P < 0.0001). The most significant associations with premalignant/malignant endometrial lesions were BMI, AUB in postmenopause, overall polyp size, atypical aspect of endometrial polyps at hysteroscopy, postmenopausal status, diabetes mellitus and patient age. Conclusions: The results of the present study suggest that the proper, aggressive or expectant, management of endometrial abnormalities should take into account both ultrasonographic and hysteroscopic findings together with the specific clinical characteristics of the patients

HLA-G and Recurrent Pregnancy Loss

Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, seems to be one of the main molecules involved in the modulation of both local and systemic maternal immune response. The prevalence of recurrent pregnancy loss (RPL), probably underestimated, is 5% of all women who achieve pregnancy, and about 40–60% percent of RPL cases are unexplained. There is an immunological analogy between allograft rejection and miscarriage, and the purpose of this review is to describe how the HLA-G pathway alterations are involved in disrupting the immunologic balance and in increasing the risk of recurrent pregnancy loss

Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways

Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs)–controlling glucosinolate content in a population of 403 Arabidopsis Bay × Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay × Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts

ESA's Ice Sheets CCI: validation and inter-comparison of surface elevation changes derived from laser and radar altimetry over Jakobshavn Isbræ, Greenland – Round Robin results

In order to increase the understanding of the changing climate, the European Space Agency has launched the Climate Change Initiative (ESA CCI), a program which joins scientists and space agencies into 13 projects either affecting or affected by the concurrent changes. This work is part of the Ice Sheets CCI and four parameters are to be determined for the Greenland Ice Sheet (GrIS), each resulting in a dataset made available to the public: Surface Elevation Changes (SEC), surface velocities, grounding line locations, and calving front locations. All CCI projects have completed a so-called Round Robin exercise in which the scientific community was asked to provide their best estimate of the sought parameters as well as a feedback sheet describing their work. By inter-comparing and validating the results, obtained from research institutions world-wide, it is possible to develop the most optimal method for determining each parameter. This work describes the SEC Round Robin and the subsequent conclusions leading to the creation of a method for determining GrIS SEC values. The participants used either Envisat radar or ICESat laser altimetry over Jakobshavn Isbræ drainage basin, and the submissions led to inter-comparisons of radar vs. altimetry as well as cross-over vs. repeat-track analyses. Due to the high accuracy of the former and the high spatial resolution of the latter, a method, which combines the two techniques will provide the most accurate SEC estimates. The data supporting the final GrIS analysis stem from the radar altimeters on-board Envisat, ERS-1 and ERS-2. The accuracy of laser data exceeds that of radar altimetry; the Round Robin analysis has, however, proven the latter equally capable of dealing with surface topography thereby making such data applicable in SEC analyses extending all the way from the interior ice sheet to margin regions. This shows good potential for a~future inclusion of ESA CryoSat-2 and Sentinel-3 radar data in the analysis, and thus for obtaining reliable SEC estimates throughout the entire GrIS

Human papillomavirus type 18 infection in a female renal allograft recipient : a case report

Publisher Copyright: © 2016 The Author(s).Background: Human papillomavirus type 18 is the second most common cause of cervical cancer and is found in 7 to 20 % of cases of cervical cancer. The oncogenic potential of high-risk human papillomavirus is associated with expression of early proteins E6 and E7. Due to long-term immunosuppressive therapy, renal transplant recipients have a higher risk of developing persistent human papillomavirus infection. Case presentation: A 29-year-old white woman from Latvia with chronic focal segmental glomerulosclerosis received renal allograft transplantation and was prescribed immunosuppressive therapy with cyclosporine, prednisolone, and mycophenolate mofetil. Two weeks after renal transplantation, her cervical swab was positive for human papillomavirus consensus sequences. After 6 months, quantitative polymerase chain reaction showed a high viral load of 3,630,789 copies/105 cells of high-risk human papillomavirus type 18 and expression of E6 and E7 oncogenes in her cervical swab and urine sample. One year after renal transplantation, the viral load in her cervical swab increased significantly to 7,413,102 copies/105 cells. Messenger ribonucleic acid of human papillomavirus type 18 E6 and E7 oncogenes were also detected. Shortly after this, she had an unsuccessful pregnancy which resulted in a spontaneous abortion at 6/7 weeks. Two months after the abortion her viral load sharply decreased to 39 copies/105 cells. Oncogenes E6 and E7 messenger ribonucleic acid expression was not observed in this period. Conclusions: This case report represents data which show that immunosuppressive therapy may increase the risk of developing persistent high-risk human papillomavirus infection with expression of E6 and E7 oncogenes in renal transplant recipients. However, even during this therapy the immune status of a recipient can improve and contribute to human papillomavirus viral load reduction. Spontaneous abortion can be considered a possible contributory factor in human papillomavirus clearance.publishersversionPeer reviewe

A Systems Biology Approach Identifies a R2R3 MYB Gene Subfamily with Distinct and Overlapping Functions in Regulation of Aliphatic Glucosinolates

BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that defend plants against both herbivores and pathogens and can attract specialized insects. Knowledge about the genes controlling glucosinolate regulation is limited. Here, we identify three R2R3 MYB transcription factors regulating aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a candidate regulator of aliphatic glucosinolates based on its co-localization within a genomic region controlling variation both in aliphatic glucosinolate content (metabolite QTL) and in transcript level for genes involved in the biosynthesis of aliphatic glucosinolates (expression QTL), as well as its co-expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29 and MYB76, were members of an Arabidopsis-specific clade that included three characterized regulators of indole glucosinolates. Over-expression of the individual MYB genes showed that they all had the capacity to increase the production of aliphatic glucosinolates in leaves and seeds and induce gene expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have reductions in only short-chained aliphatic glucosinolates whereas a mutant in MYB28 has reductions in both short- and long-chained aliphatic glucosinolates. Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an emergent property of the system since the absence of aliphatic glucosinolates in these plants could not be predicted by the chemotype of the single knockouts. CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory genes have evolved both overlapping and specific regulatory capacities. This provides a unique system within which to study the evolution of MYB regulatory factors and their downstream targets

Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection

Funding Information: RFBR grant 17–54-30002, Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075–15–2019-1660) to Olga Smirnova. Publisher Copyright: © 2021, The Author(s).Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.publishersversionPeer reviewe