Interaction effect of mutations in the genes (piwi and aub) of the Argonaute family and hobo transposons on the integral survival parameters of Drosophila melanogaster.

The Argonaute family genes (piwi and aub) involved in the production of small RNAs are responsible for the regulation of many cellular processes, including the suppression of genome instability, modulation of gene activity, and transposable elements. Dysfunction of these genes and the associated activation of transposable elements adversely affect reproductive development and quality of life. The role of transposons in contrast to retrotransposons and their interaction with genes of the Argonaute family in aging processes have not been studied. This study considers a scenario in which the piwi and aub genes in the presence of functional hobo transposons can modify the effects from the level of DNA damage to lifespan. The simultaneous presence of mutation (piwi or aub) and hobo (regardless of size) in the genome has practically no effect or (less often) leads to a decrease in the level of DNA damage in ovarian cells. A high level of sterility and low ovarian reserve were noted mainly with a combination of mutations and full-sized hobo elements. The combination of these two genetic factors negatively affects the fertility of young females and embryonic survival. Isolated cases of restoration of reproductive functions with age were noted but only in females that had low fertility in the early period of life. The presence of hobo transposons contributed to an increase in the lifespan of both mutant and non-mutant females. Dysfunction of the piwi and aub genes (without hobo) can reduce the lifespan of both sexes. Together, each mutation and hobo transposons act antagonistically/additively (in females) and synergistically/antagonistically (in males) to change the lifespan. In parameters of locus-specific instability, hobo activation was more pronounced in piwi gene dysfunction. The results obtained complement data on the study of new functions of Argonaute family genes and their interactions with transposable elements in the aging process.

Unmet needs in abnormal uterine bleeding due to ovulatory dysfunction.

Ovulatory disorders are a common cause of abnormal uterine bleeding in women of reproductive age. The International Federation of Gynecology and Obstetrics currently offers a causal classification system for ovulatory disorders but does not provide clear management recommendations. There remains regional disparity in treatment practices, often influenced by institutional and insurance regulations as well as cultural and religious practices. A panel of experts evaluated current gaps in ovulatory disorder management guidelines and discussed potential strategies for addressing these unmet needs. Key gaps included a lack in consensus about the effectiveness of combined estrogen and progestogen versus progestogen alone, a paucity of evidence regarding the relative effectiveness of distinct hormonal molecules, a lack of data regarding optimal treatment duration, and limited guidance on optimal sequencing of treatment. Recommendations included development of a sequential treatment-line approach and development of a clinical guide addressing treatment scenarios common to all countries, which can then be adapted to local practices. It was also agreed that current guidelines do not address the unique clinical challenges of certain patient groups. The panel discussed how the complexity and variety of patient groups made the development of one single disease management algorithm unlikely; however, a simplified, decision-point hierarchy could potentially help direct therapeutic choices. Overall, the panel highlighted that greater advocacy for a tailored approach to the treatment of ovulatory disorders, including wider consideration of non-estrogen therapies, could help to improve care for people living with abnormal uterine bleeding due to ovarian dysfunction.

Ultrasound-Guided Polypectomy: Evaluation of a Novel Technique to Remove Endometrial Polyps in the Office.

OBJECTIVE: To present a novel technique for office resection of pedunculated endometrial polyps under ultrasound guidance. METHODS: A prospective trial was conducted at an academic center where women with abnormal uterine bleeding (AUB) who were diagnosed an endometrial polyp following saline infusion sonogram (SIS), were offered polyp removal under ultrasound guidance using a universal grasping forceps (2.5 mm × 25 cm). The primary outcome was to evaluate the feasibility of this technique for complete removal of the polyp. The secondary outcomes were to evaluate the patients' pain score, satisfaction score using visual analogue score (VAS), and efficacy of the technique in alleviating symptoms in patients with AUB due to polyps. RESULTS: Thirty patients participated, with a mean age of 54.8 ± 11 years. Average polyp volume was 1.87 cm3 and mean duration for polypectomy was 11 minutes 31 seconds. The median pain score immediately post-procedure was 5 (0-9). We were unable to complete the procedure in two patients due to patient discomfort and poor visualization. Complete removal of polyp was ensured by checking for a thin endometrial echo at the end of the procedure and by performing SIS at 3-months post-procedure. Of the 22 patients who returned for follow-up, 19 (86.36%) showed no evidence of polyp on SIS and all reported resolution of AUB symptoms. The median satisfaction score at the follow-up was 10/10. Adequate pathology samples were obtained from all cases, diagnosing malignancy in one and endometrial hyperplasia in one patient. CONCLUSION: This technique offers safe and effective removal of pedunculated endometrial polyps in an office setting, avoiding the need for general anesthesia. It can be offered as a therapeutic option at the initial point of contact, providing symptom relief and tissue diagnosis while reducing costs and patient visits.

Standardising outcome reporting for clinical trials of interventions for heavy menstrual bleeding: Development of a core outcome set.

OBJECTIVE: To develop a core outcome set for heavy menstrual bleeding (HMB). DESIGN: Core outcome set (COS) development methodology described by the COMET initiative. SETTING: University hospital gynaecology department, online international survey and web-based international consensus meetings. POPULATION OR SAMPLE: An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents. METHODS: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. MAIN OUTCOME MEASURES: Outcome importance was assessed in the Delphi survey on a 9-point scale. RESULTS: From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. CONCLUSIONS: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy.

National survey of abnormal uterine bleeding according to the FIGO classification in Japan.

AIM: To investigate the status of abnormal uterine bleeding (AUB) in Japan using the International Federation of Gynecology and Obstetrics (FIGO) classification (AUB system 1 and 2; PALM-COEIN) and to clarify the relationship between AUB symptoms and the diseases causing AUB. METHODS: In a nationwide study, we enrolled first-time patients who visited target facilities during two consecutive weeks from December 1, 2019 to January 31, 2020. The FIGO classification was used to investigate patients with symptoms and causative diseases of AUB. Based on the proportion of patients in the nationwide study, 373 cases were included in the detailed survey. Survey items included symptoms of AUB according to AUB system 1, examination details, and causative diseases according to the PALM-COEIN classification. RESULTS: Within the study period, we encountered 61 740 first-time patients, of which 8081 (13.1%) were diagnosed with AUB. Among them, 39.9% had abnormal menstrual cycles and 56.9% had abnormal menstrual bleeding. In the survey, PALM had the highest percentage of AUB-L and COEIN had the highest percentage of AUB-O. Correspondence analysis showed that COEIN was strongly associated with abnormal menstrual cycles and PALM with abnormal menstrual bleeding. CONCLUSION: We conducted the first nationwide survey of AUB in Japan. The FIGO classification was a useful tool for the diagnosis of AUB, with a strong correlation between symptoms of AUB by AUB system 1 and the causative disease of AUB by PALM-COEIN. Conversely, a high percentage of AUB-N and AUB-E suggests that AUB system 1 and PALM-COEIN are ambiguous as diagnostic tools.

Electronic Structure and Chemical Bonding of the First-, Second-, and Third-Row-Transition-Metal Monoborides: The Formation of Quadruple Bonds in RhB, RuB, and TcB.

Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.

PICKLE associates with histone deacetylase 9 to mediate vegetative phase change in Arabidopsis.

The juvenile-to-adult vegetative phase change in flowering plants is mediated by a decrease in miR156 levels. Downregulation of MIR156A/MIR156C, the two major sources of miR156, is accompanied by a decrease in acetylation of histone 3 lysine 27 (H3K27ac) and an increase in trimethylation of H3K27 (H3K27me3) at MIR156A/MIR156C in Arabidopsis. Here, we show that histone deacetylase 9 (HDA9) is recruited to MIR156A/MIR156C during the juvenile phase and associates with the CHD3 chromatin remodeler PICKLE (PKL) to erase H3K27ac at MIR156A/MIR156C. H2Aub and H3K27me3 become enriched at MIR156A/MIR156C, and the recruitment of Polycomb Repressive Complex 2 (PRC2) to MIR156A/MIR156C is partially dependent on the activities of PKL and HDA9. Our results suggest that PKL associates with histone deacetylases to erase H3K27ac and promote PRC1 and PRC2 activities to mediate vegetative phase change and maintain plants in the adult phase after the phase transition.

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.

Should body mass index replace age to drive the decision for endometrial sampling in premenopausal women with abnormal uterine bleeding?

OBJECTIVE: This study aimed to evaluate risk factors for endometrial intraepithelial neoplasia/malignancy in premenopausal women with abnormal uterine bleeding or oligomenorrhea. Specifically, we aimed to elucidate whether body mass index (BMI) or age confers a higher risk. STUDY DESIGN: A retrospective cohort study was performed at a large academic center examining risk factors for endometrial hyperplasia/malignancy in premenopausal women undergoing endometrial sampling. RESULTS: Of the 4170 women ages 18-51 who underwent endometrial sampling from 1987 to 2019, 77 (1.85%) were found to have endometrial intraepithelial neoplasia or malignancy. Clinical predictors of EIN/malignancy in this population included obesity (OR: 3.84, 95%, p < .001), Body mass index [(OR30 vs. 25:2.11, p < .001) and OR35 vs. 30: 1.65, p < .001], Diabetes (OR: 3.6, p-value <.001), hormonal therapy use (OR: 2.93, p < .001), personal history of colon cancer (OR: 9.90, p = .003), family history of breast cancer (OR: 2.65, p < .001), family history of colon cancer (OR: 3.81, p < .001), and family history of endometrial cancer (OR: 4.92, p = .033). Age was not significantly associated with an increased risk of disease. Adjusting for other factors, a model using BMI to predict the risk of EIN/malignancy was more discriminative than a model based on age. CONCLUSIONS: Increased BMI, may be more predictive of endometrial hyperplasia/malignancy than age in premenopausal women with abnormal uterine bleeding. Modification of evaluation guidelines in a contemporary demographic setting could be considered.

The reproductive endocrine feature and conception outcome of women with unknown etiological menstrual cycle (36-45 days) with long follicular phase.

OBJECTIVE: To explore the reproductive endocrine feature and conception outcome of women with unknown etiological long menstrual cycle (LMC) (36-45 days) with long follicular phase. METHODS: In the cohort study, we included 80 women with unknown etiological long menstrual cycle of biphasic basal body temperature (BBT) lasting for 36-45 days and 87 controls with normal cycle of biphasic BBT into LMC group and NMC group, respectively. Serum hormone levels, fasting glucose, and insulin of participants were tested, and ovulation was observed by ultrasound. The conception outcome was followed up within 12 menstrual cycles. RESULTS: In the LMC group, the rate of abnormality of HOMA-insulin resistance index (40.0% vs. 20.7%, p < .01), luteal phase defect (30.9% vs. 13.8%, p < .05) and abnormality of FSH/LH ratio (15.6% vs. 5.7%, p < .05) were all significantly higher, but the serum estradiol level on the day before ovulation (261.10 pg/mL vs. 320.26 pg/mL, p < .01) was lower. The rate of poor ovulation quality (31.3% vs.15.4%, p < .05) in the LMC group was significantly higher than the NMC group. In the LMC group, the natural conception rate within 12 menstrual cycles was lower (41.9% vs. 66.2%, p < .01), whereas the spontaneous abortion rate in early pregnancy (29.0% vs. 9.8%, p < .05) and the conversion rate (21.6% vs. 5.2%, p < .01) to anovulation within 12 cycles were significantly higher. CONCLUSIONS: Women with unknown etiological menstrual cycle (36-45 days) with long follicular phase have greater endocrine abnormality and higher risk of spontaneous abortion, infertility, and conversion to anovulation. Moderate early intervention may be advisable for these women, especially those who wish to get pregnant.

Efficacy of Uterine Artery Embolization for Treatment of Anticoagulant-Associated Abnormal Uterine Bleeding.

STUDY OBJECTIVE: Data regarding uterine artery embolization (UAE) to specifically treat anticoagulant-associated iatrogenic abnormal uterine bleeding (AUB-I) are sparse. This manuscript aimed to quantify the effectiveness of UAE in treating this subset of patients. DESIGN: Retrospective case series. SETTING: Academic hospital serving a large minority-majority population. PATIENTS: Twenty-four patients with AUB-I that was provoked or aggravated by the initiation of anticoagulation therapy. INTERVENTIONS: Treatment of anticoagulant-associated AUB-I that failed medical management or was acute with UAE rather than inferior vena cava filter placement and hysterectomy. MEASUREMENTS AND MAIN RESULTS: An imaging database search was performed to identify patients who underwent UAE for anticoagulant-associated AUB-I from May 2011 to July 2020. Medical and radiologic records were reviewed. Short- and long-term outcomes were obtained to date, ranging from 10 months to 10 years after the procedure. In total, 24 patients were identified, ranging in age from 35 to 54 (mean 44.9) years. Venous thromboembolic disease was the most common (92%) indication for anticoagulation. At presentation, 14 patients (58%) were anticipated to require lifelong anticoagulation. Most UAE procedures (54%) occurred within 10 days of anticoagulation initiation. Before UAE, 17 patients (71%) attempted and failed medical management, myomectomy, or endometrial ablation to control bleeding. After UAE, 21 patients (88%) experienced substantial improvement or resolution of AUB and continued anticoagulation therapy. Three patients (14%) did not experience improvement and were treated with hysterectomy. Amenorrhea immediately after UAE occurred in 1 patient at age 45. CONCLUSION: UAE was an effective tool in the management of anticoagulant associated AUB-I in this cohort, resulting in decreased bleeding while allowing the continuation of anticoagulation therapy, with high rates of uterine preservation and preserved menses.

Ferric carboxymaltose for treatment of iron deficiency and iron deficiency anemia caused by abnormal uterine bleeding.

Introduction: Heavy menstrual bleeding leads to depletion of iron stores, with subsequent iron deficiency (ID) and iron deficiency anemia (IDA). To evaluate the efficacy and safety of ferric carboxymaltose (FCM) in treatment of ID/IDA caused by abnormal uterine bleeding (AUB). Material and methods: One hundred and twenty women ≥ 40 years old with chronic AUB and ID/IDA were included in this study for correction of ID/IDA. Participants received FCM infusion for correction of ID/IDA. The pre-treatment ferritin, hemoglobin (Hb), red blood cell (RBC) mean corpuscular volume (MCV), and RBC mean corpuscular hemoglobin (MCH) values were compared with the 6- and 12-week post-treatment values. Results: The pre-treatment ferritin and Hb levels significantly increased from 13.2 ±7.4 µg/l and 8.8 ±0.8 g/dl, respectively, to 111.5 ±5.6 µg/l and 13.9 ±0.6 g/dl, respectively, 6 weeks after FCM (p = 0.001 and 0.0009; respectively), and to 98.7 ±6.1 µg/l and 12.9 ±0.65 g/dl, respectively, 12 weeks after FCM (p = 0.01 and 0.01; respectively). In addition, the pre-treatment RBC MCV and RBC MCH values significantly increased from 74.3 ±2.3 fl and 26.6 ±5.3 pg, respectively, to 88.7 ±1.9 fl and 29.6 ±4.5 pg, respectively, 6 weeks after FCM (p = 0.01 and 0.03, respectively), and to 93.3 ±1.75 fl and 30.3 ±3.8 pg, respectively, 12 weeks after FCM (p = 0.001 and 0.0001, respectively). Conclusions: FCM was safe and effective for correction of ID/IDA caused by chronic AUB within 6 weeks. The serum ferritin, Hb, and RBC indices remained significantly high compared to the pre-treatment values 12 weeks after FCM infusion.

RSF1 in cancer: interactions and functions.

RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

Performance of the AUB-HAS2 Cardiovascular Risk Index in vascular surgery patients.

The American University of Beirut (AUB)-HAS2 risk index is a recently published tool for preoperative cardiovascular evaluation. It is based on six data elements: history of Heart disease, symptoms of Heart disease (angina or dyspnea), Age ⩾ 75 years, Anemia (hemoglobin < 12 mg/dL), emergency Surgery, and vascular Surgery. This study analyzes the performance of a modified AUB-HAS2 index (excluding the vascular surgery element) in a broad spectrum of vascular surgery procedures. The study population consisted of 90,476 vascular surgeries registered in the American College of Surgeons National Surgical Quality Improvement Program database. The performance of the AUB-HAS2 index was studied in seven groups: carotid endarterectomy (CEA), open abdominal aortic aneurysm surgical repair (OAAA), endovascular aortic aneurysm repair, supra-inguinal bypass, infra-inguinal bypass, lower extremity thrombo-endarterectomy, and lower extremity angioplasty. The outcome measure was death, myocardial infarction, or stroke at 30 days after surgery. Each patient was given an AUB-HAS2 score of 0, 1, 2, or > 2 depending on the number of data elements s/he has. The AUB-HAS2 index was able to stratify risk in the majority of patients into low (< 3%, score 0), intermediate (3-10%, score 1-2), and high (> 10%, score > 2) (p < 0.0001). The receiver operating curve had an area of 0.71 in the overall group and it ranged from 0.60 in CEA patients to 0.75 in OAAA patients. In conclusion, the AUB-HAS2 index is a simple tool that can quickly and effectively stratify the risk of patients undergoing a broad spectrum of vascular surgeries into low, intermediate, and high.

Hysteroscopic endometrial biopsy: from indications to instrumentation and techniques. A call to action.

During the last twenty years, the diagnostic approach to endometrial pathology has radically evolved. For over a century, intrauterine blind biopsy techniques were considered the gold standard procedure for the histopathological diagnosis of intrauterine diseases. The advent of hysteroscopy, which made it possible to directly visualize the uterine cavity, and the subsequent miniaturization of the instruments allowing its use in the office setting without anesthesia are considered game-changers. To date, it is feasible to retrieve a targeted eye specimen of endometrial tissue with little or no discomfort for the patient in the office setting. To pursue this aim, several technological upgrades have improved the diagnostic accuracy of hysteroscopic endometrial biopsy. In this paper we provide an up-to-date review of the latest evidence regarding indications, instrumentations, and techniques for hysteroscopic endometrial biopsy, to help the operator in providing an adequate endometrial sampling for histopathological analysis.

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.

Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification. RSF1 associates specifically with H2Aub, but not H2Bub nucleosomes, through a previously uncharacterized and obligatory region designated as ubiquitinated H2A binding domain. In human and mouse cells, genes regulated by RSF1 overlap significantly with those controlled by RNF2/Ring1B, the subunit of Polycomb repressive complex 1 (PRC1) which catalyzes the ubiquitination of H2AK119. About 82% of H2Aub-enriched genes, including the classic PRC1 target Hox genes, are bound by RSF1 around their transcription start sites. Depletion of H2Aub levels by Ring1B knockout results in a significant reduction of RSF1 binding. In contrast, RSF1 knockout does not affect RNF2/Ring1B or H2Aub levels but leads to derepression of H2Aub target genes, accompanied by changes in H2Aub chromatin organization and release of linker histone H1. The action of RSF1 in H2Aub-mediated gene silencing is further demonstrated by chromatin-based in vitro transcription. Finally, RSF1 and Ring1 act cooperatively to regulate mesodermal cell specification and gastrulation during Xenopus early embryonic development. Taken together, these data identify RSF1 as a H2Aub reader that contributes to H2Aub-mediated gene silencing by maintaining a stable nucleosome pattern at promoter regions.

Study of causes behind abnormal uterine bleeding according to PALM- COEIN classification at a tertiary care hospital.

This descriptive observational study was carried out to determine the frequency of causes behind Abnormal Uterine Bleeding (AUB) amongst patients of reproductive age presenting to gynaecology OPD from January to June 2018 at the Combined Military Hospital Kharian, a tertiary care hospital. All women presenting with complaints of AUB were enrolled for the study, except for those who were pregnant, adolescent and postmenopausal. Detailed history, physical examination and relevant investigations were done and patients were categorised according to FIGO PALM-COEIN classification system and placed in nine main categories. A total of 238 patients were enrolled and the incidence of AUB among them was found to be 11% according to PALM-COEIN classification system. The frequency and percentage of all etiologies was calculated. Frequency of structural causes was Polyp 10 (6.7%), Adenomyosis 35 (23.5%), Leiomyomata 80 (53.7) and Malignancy 24 (16.1%). Nonstructural causes were Coagulation Disorders 5 (5.6%), Ovulatory 56 (37.6%), Endometrial Dysfunction 3 (3.4%), Iatrogenic 14 (15.7%) and Not-yet-classified 11 (12.4%). Development of a universally accepted classification system is a step towards facilitating clinicians, patients and researchers to communicate with each other and make objective management plans.

Analysis of the results of invasive diagnostic procedures in patients referred to gynecologic department due to abnormal uterine bleeding.

INTRODUCTION: Abnormal uterine bleeding (AUB) is one of the most common reason for visits to gynecologists. Endometrial biopsy is a routine procedure in gynecological practice to detect the etiology of AUB and to exclude precancerous and cancerous lesions of the endometrium. The aim of this study was to assess the causes of AUB among women, who had undergone invasive diagnostics due to AUB. MATERIAL AND METHODS: This study was carried among 531 women, who had undergone invasive diagnostics due to AUB between January 2018 and December 2018. Women were divided into premenopausal (with perimenopausal) and postmenopausal groups. Transvaginal ultrasound was performed. Endometrial thickness was compared with histopathological results in each subgroup and statistically analyzed. The incidence of histopathological findings and rate of anemia were also analyzed. RESULTS: In our series of patients the most common cause of AUB based on histopathological results was endometrial polyp, both before and after menopause. The most frequent pathologies at ultrasound findings were leiomyomas and endometrial polyps. The incidence of taken together: atypical hyperplasia and endometrial cancer was significantly higher in postmenopausal group (8.58%) than in pre- and perimenopausal (1.35%, p = 0.0001). The median endometrial thickness, both before and after menopause, was significantly greater in patients with pathological than with nonpathological endometrium. 31% of women with abnormal uterine bleeding before menopause and 10% after menopause had anemia. CONCLUSIONS: Measurements of endometrial thickness seems to be acceptable initial diagnostic tool to distinguish between benign and pathological endometrial changes both before and after menopause.

The Pax protein Eyegone (Eyg) interacts with the pi-RNA component Aubergine (Aub) and controls egg chamber development in Drosophila.

The eyegone (eyg) gene encodes Eyg, a transcription factor of the Pax family with multiple roles during Drosophila development. Eyg has been shown to be nuclear in the cells where it functions. In this report we describe a new functional cytoplasmic distribution of Eyg during egg chamber development in the female ovarioles. The protein is present from the germarium until stage 10 of cyst development. The majority of egg chambers that develop in the absence of Eyg arrest their development before stage 10, show augmented levels of the telomeric retro-transposon TART-A and low levels of heterochromatin marks in the oocyte nucleus. During the maternal to zygotic transition (MTZ) Eyg seems to play a role in destabilizing germ cell less (gcl) and oo 16 RNA binding protein (orb) mRNAs. We were able to show that Eyg interacts with Aubergine (Aub), a component of the pi-RNA pathway during egg chamber development. This interaction could be essential for Eyg to be retained in the cytoplasm and fulfill its functions there.

Resolution of Uterine Arteriovenous Malformation and Maintenance of Reproduction in 20 Women Treated with a GnRH Agonist Concomitantly with an Aromatase Inhibitor and Tranexamic Acid.

OBJECTIVE: This study investigated the efficacy of GnRH agonists concomitantly with transient aromatase inhibitor and tranexamic acid to treat women with uterine arteriovenous malformations (AVMs) associated with abnormal uterine bleeding (AUB) to preserve fertility and determine reproductive outcome. METHODS: This was a prospective cohort study in a tertiary centre. Doppler ultrasound demonstrated AVM in 19 women with AUB 1-28 weeks following spontaneous or therapeutic abortion and in one woman 4 years after normal pregnancy while taking an oral contraceptive. On the basis of experience from the first three cases, 17 women were treated with tranexamic acid (1 g three times daily orally for 5 days), a GnRH agonist (3.75-11.25 mg, for 1-3 months), plus an aromatase inhibitor (letrozole 2.5 mg once daily for 5days) with the initial injection of GnRH agonist. Two women required blood transfusion, and one required uterine tamponade with Foley catheter balloon in the first 48 hours to control heavy bleeding (Canadian Task Force Classification II-2). RESULTS: All 20 AVMs resolved within 1-3 months of treatment. Of 16 women who attempted pregnancy, all (100%), including two who had uterine artery embolization (one after hysteroscopic septoplasty), conceived spontaneously with 18 live births. Two women are using contraception (one taking an oral contraceptive, one using a levonorgestrel intrauterine system), and one 40-year-old is not using contraception. One woman had hysteroscopic endometrial ablation followed by vaginal hysterectomy for AUB at 1 and 2 years later. CONCLUSION: A GnRH agonist in combination with transient aromatase inhibitor and tranexamic acid is an effective management strategy to treat and maintain reproduction in women with AVMs associated with AUB.