Immunohistochemical localization of selected pro-inflammatory factors in uterine myomas and myometrium in women of various ages

Uterine myomas represent one of the most frequently manifested benign tumors in women. They originate from smooth muscle cells of myometrium or its blood vessels. Many studies suggest that inflammation and pro-inflammatory factors may play a role in the carcinogenesis with an involvement of the transcription factor NF-kappaB which activity can be controlled by various environmental factors, including many cytokines. The aim of the study was to investigate the expression of NF-B, interleukin-1β (IL-1β), tumor necrosis factor a (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in myometrium and uterine myomas of women of various age. The expression of NF-kappaB, selected cytokines and enzymes was estimated in women of reproductive or perimenopausal age by semiquantitative immunohistochemistry. The expression of the examined proteins was higher in myomas than in control myometrium and was dependent on the size of myomas and the age of women. However, the expression of the cytoplasmic NF-kappaB observed in uterine myomas was independent on the size of myomas and no significant differences were observed in the number of stained nuclei between control and myoma groups. Thus, the expression of proinflammatory factors in myomas was not accompanied by the nuclear activation of NF-kappaB p65. The results of our study indicate that the examined factors may be involved in the pathogenesis of benign tumors and not only malignant diseases. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 73–83

Fresh insight into premature ovarian insufficiency

Premature ovarian insufficiency (POI) is one of the vital reasons of anovulatory infertility among women under 40 years old. However, because of the unacknowledged causative factor in most cases, it still remains a huge challenge in gynecology. Recently, the most promising opportunities in diagnosing are connected with the use of some serum biomarkers, such as interleukin-17 (IL-17), Frizzled-5 protein, Soggy-1 protein and other cytokines. Additionally, environmental toxicants such as chemicals and heavy metals might be relevant in the near future when investigating the causes of premature ovarian insufficiency. One of the main aims of the therapy is to focus on maintaining fertility among women with POI, since it is essential for patients considering their young age. Among the newest approaches listed there are different types of stem cells, oocytes donation and in-vitro activation, all of which are recently gaining in importance

Circulating omentin-1 levels and inflammation in polycystic ovary syndrome

Objectives: The aim of the study was to analyze interrelation between plasma omentin-1 levels and nutritional status andinflammation in PCOS.Material and methods: A cross-sectional study involving 86 PCOS (47 obese) and 72 Non-PCOS women (41 obese) determinedanthropometric parameters and body composition. Serum glucose, insulin and omentin-1, TNF-α, sTNFRs, IL-6 andsR-IL6 were measured in the fasting state.Results: Plasma omentin-1 levels were significantly lower in the PCOS than in the Non-PCOS group and both correspondingnormal weight and obese subgroups. In three analyzed least-angle regression (LARS) models the lower plasma omentin-1 levels was associated with PCOS occurrence, higher circulating TNF-α and lower IL-6 levels.Conclusions: Suppressed omentin-1 levels in PCOS are characteristic for this disturbance and proinflammatory cytokinesare factors modifying secretion of this adipokine

Circulating vaspin levels and nutritional status and insulin resistance in polycystic ovary syndrome

Objectives: The study aimed to assess the associations between circulating vaspin levels and nutritional status (assessedon tha basis of BMI) as well as insulin resistance in PCOS.Material and methods: Eighty-seven PCOS women, 48 obese and 39 normal weight, were enrolled in the cross-sectionalstudy. Seventy-two Non-PCOS women, 41 obese and 31 normal weight, constituted a control group. Body mass, height andwaist circumference as well as body composition by bioimpedance were measured. In the morning (16h after the last meal)we determined: serum glucose, insulin, androgens, gonadotropin (LH, FSH) and sex hormone-binding globulin (SHBG) aswell as plasma vaspin levels. Standard HOMA-IR formula was used to assess insulin resistance (IR).Results: Plasma vaspin levels were significantly lower in PCOS, both normal weight and obese, than in Non-PCOSgroups. Vaspin levels were similar in normal weight and obese PCOS subgroups. There was no association between plasmavaspin levels and anthropometric parameters in PCOS group. While in Non-PCOS group a negative correlation betweenplasma vaspin levels and body mass (r = –0.26; p < 0.05) was found. We did not observe correlations between plasma vaspinlevels and serum glucose and insulin concentrations as well as HOMA-IR values, however, in multivariable, stepwise backwardregression waist circumference and HOMA-IR values explained 18.0% of plasma vaspin levels variability in the study subjects.Conclusions: PCOS occurrence is associated with decreased vaspin levels. The influence of nutritional status on vaspin levelobserved in Non-PCOS is abolished in PCOS women, possibly by more severe insulin resistance

A comprehensive use of ultrasound examination in infertility workup

Considering the growing availability of ultrasound diagnostic methods in gynecology, its role in the infertility setting is increasing. In this review, we present an up-to-date ultrasound based diagnostic scheme in infertility workup comprising the evaluation of ovarian anatomy and function, uterine exploration, as well as tubal patency. The possibility of performing the vast majority of infertility diagnostics by ultrasound in the ambulatory settings is not only attractive and beneficial to patients, but also to health care system. Thus, it is vital for gynecologists to implement modern non-invasive ultrasound modalities in their everyday practice

Cell-by-cell dissection of phloem development links a maturation gradient to cell specialization

Publisher Copyright: Copyright © 2021 The Authors, some rights reserved;In the plant meristem, tissue-wide maturation gradients are coordinated with specialized cell networks to establish various developmental phases required for indeterminate growth. Here, we used single-cell transcriptomics to reconstruct the protophloem developmental trajectory from the birth of cell progenitors to terminal differentiation in the Arabidopsis thaliana root. PHLOEM EARLY DNA-BINDING-WITH-ONE-FINGER (PEAR) transcription factors mediate lineage bifurcation by activating guanosine triphosphatase signaling and prime a transcriptional differentiation program. This program is initially repressed by a meristem-wide gradient of PLETHORA transcription factors. Only the dissipation of PLETHORA gradient permits activation of the differentiation program that involves mutual inhibition of early versus late meristem regulators. Thus, for phloem development, broad maturation gradients interface with cell-type-specific transcriptional regulators to stage cellular differentiation.Peer reviewe

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Non-obvious diagnosis and breast development in pure gonadal dysgenesis

Pure gonadal dysgenesis is a situation when the karyotype is 46, XY, but for various reasons there is a disorder of differentiation of Wolffian and Mullerian structures and in consequence the phenotype is female. It is known that abdominal gonads and the presence of Y chromosome allow to qualify this condition as a high risk of tumor. In most cases breast development is limited because of lack or low level of estrogen. A 27-year-old patient with differences of sexual development (DSD), was admitted to the Department of Endocrinological Gynecology for a control examination. In the history: dysgerminoma, primary amenorrhea and ambiguous karyotype. The patient has not taken hormonal replacement therapy. The breast development is Tanner stage V

Macro-TSH — tips and tricks for gynecologists

Thyroid disorders are one of the most common endocrinopathies in women of reproductive age. Measurement of TSH (thyroid-stimulating hormone) concentration in women planning pregnancy/pregnant is a golden standard of thyroid function assessment. When the laboratory findings do not correspond with the clinical signs, it is reasonable to mark macro-TSH