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Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)—participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2–3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns. [ABSTRACT FROM AUTHOR]

The human conjunctival epithelial cells (HCEC) line the inner sides of the eyelids and the anterior part of the sclera. They include goblet cells that secret mucus into the tear film that protects the ocular surface. The conjunctival epithelium is subjected to mechano-physical stimuli due to eyelid movement during blinking, during wiping and rubbing the eyes, and when exposed to wind and air currents. We cultured primary HCEC under air–liquid interface (ALI) conditions in custom-designed wells that can be disassembled for installation of the in vitro model in a flow chamber. We exposed the HCEC after ALI culture of 8–10 days to steady and oscillatory airflows. The in vitro model of HCEC was exposed to steady wall shear stresses (sWSS) of 0.5 and 1.0 dyne/cm2 for lengths of 30 and 60 min and to oscillatory wall shear stresses (oWSS) of 0.5 and 0.77 dyne/cm2 amplitudes for a length of 10 min. Cytoskeletal alterations and MUC5AC mucin secretion in response to WSS were investigated using immunohistochemically fluorescent staining and enzyme-linked lectin assay (ELLA), respectively. The results revealed that both exposure times and sWSS values increased the polymerization of F-actin filaments while mucin secretion decreased. However, after a recovery of 24 h in the incubator we observed a decrease of F-actin fibers and mucin secretion only for exposure of 30 min. The length of exposure was more influential on cytoskeletal alterations than the level of sWSS. The very small effect of sWSS on mucin secretion is most likely related to the much smaller amount of goblet cell than in other mucus-secreting tissue. The results for both oWSS amplitudes revealed similar trends regarding F-actin and mucin secretion. Immediately post-exposure we observed an increase in polymerization of F-actin filaments while mucin secretion decreased. However, after 24-h recovery we observed that both F-actin and mucin secretion returned to the same values as for unexposed cultures. The results of this study suggest that WSS should be considered while exploring the physiological characteristics of HCEC. [ABSTRACT FROM AUTHOR]

The human uterus is composed of three layers: endometrium, myometrium and perimetrium. It remodels during the monthly menstrual cycle and more significantly during the complex stages of reproduction. In vivo studies of the human uterine wall are yet incomplete due to ethical and technical limitations. The objective of this study was to develop in vitro uterine wall models that mimic the in vivo structure in humans. We co-cultured multiple cellular models of endometrial epithelial cells, endometrial stromal cells and smooth muscle cells on a synthetic membrane mounted in multi-purpose custom-designed wells. Immunofluorescence staining and confocal imaging confirmed that the new model represents the in vivo anatomical architecture of the inner uterine wall. Hormonal treatment with progesterone and β-estradiol demonstrated increased expression of progestogen-associated endometrial protein, which is associated with the in vivo receptive uterus. The new tissue-engineered in vitro models of the uterine wall will enable deeper investigation of molecular and biomechanical aspects of the blastocyst–uterus interaction during the window of implantation. [ABSTRACT FROM AUTHOR]

Adenomyosis is a disease in which ectopic endometrial glands and stromal cells appear in the uterine myometrium. This pathology is common among women of reproductive age, and in addition to chronic pelvic pain and heavy periods it may also cause infertility. The 'tissue injury and repair' mechanism in response to increased intrauterine pressures was proposed as the etiology for migration of fragments of basal endometrium into the myometrial wall. In order to investigate this mechanism, a conceptual two-dimensional model of the uterine wall subjected to intrauterine pressures was implemented using ADINA commercial software. The stress field within the uterine wall was examined for a variety of intrauterine sinusoidal pressure waves with varying frequencies. The results revealed that: (1) as the wavelength of the subjected pressure wave decreased, high concentration of stresses developed near the inner uterine cavity; (2) as the pressure wave frequency increased, high gradients of the stresses were obtained; (3) at menstrual phase, the highest stresses obtained at the endometrial-myometrial interface. Therefore, increased uterine activity results in high stresses which may lead to tissue lesions and detachment of endometrial cells. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) cells depend on their microenvironment for proliferation and survival. Ectonucleotidase CD39 has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death. In this study, we investigated the clinical significance of CD39 expression on CD4 T cells in 62 patients with CLL as well as its compartmental regulation and explored the possible mechanisms for its induction. Compared to healthy individuals, CD4CD39 lymphocytes were increased in the peripheral blood of patients with CLL and correlated with the advanced stage of disease. CD4CD39 cells were also higher in patients with CLL, who needed therapeutic intervention, and in those who had unmutated immunoglobulin heavy chain variable region gene, were ZAP70 or had β2-microglobulin levels of >3 g/L. There were more CD4CD39 lymphocytes in the bone marrow compartment than in the peripheral blood, and in vitro studies showed that CD39 can be induced on CD4 cells by exposure to ATP or indirectly, following B cell receptor engagement. This may support the notion that the leukemic cells contribute to create an immune-subversive environment, and perhaps to a poorer prognosis. CD39 may also serve as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL. [ABSTRACT FROM AUTHOR]

Introduction: Survivin is a member of inhibitor of apoptosis protein family which suppresses apoptosis and regulates cell division. Survivin was not found to be expressed in normal differentiated tissues. CD95 is a cell surface receptor, and it is believed to induce cell death in a variety of cells. The goal of this study is to evaluate the survivin and CD95 expression in bladder and uerters of children operated for vecsicoureteral reflux (VUR). Materials and methods: Sixteen paraffine embeded ureteral units of 11 children with vescico ureterl reflux were treated immunohistochemicaly with survivin and CD95. At operation the distal margins of the ureters were send to histologic exam and a full thickness biopsy from the anterior bladder wall including muscle and mucosa were performed. The control was taken from a urologically normal 9 days old baby who died from myocarditis. The sections were stained with the antibody in the regular method and the degree of staining was graded from 0 to 3, by a single uropathologist. Results: Immunohistochemistry staining with survivin was positive in all ureters. We had 13 high grade (grade 3–5) and 3 low grade (grade 1–2) vesicoureteral reflux. The average survivin degree of staining in the low grade reflux was 1.33 compared to 2.3 (P = 0.019) in the high grade refluxing ureters. The staining of the control sample was graded 1. The average degree of staining was 1.2 in the bladder wall compared to 2.125 in the ureters. CD95 stained mast cells in ureters and bladders. Conclusions: Possitive staining of survivin was found in both ureters and urinary bladders of children that underwent surgical repair of vesicoureteral reflux. The degree of survivin staining was significantly higher in the high grade refluxing ureters compared to low grade reflux and to the bladder wall in the same patients. [ABSTRACT FROM AUTHOR]

This study evaluated the ability of hysteroscopy to preoperatively predict cervical involvement in endometrial cancer. The records of 110 surgically staged consecutive endometrial cancer patients treated at our institution from 1997 to 2003 were retrospectively analyzed. Data on demographics, preoperative staging procedures, surgical pathology reports, and adjuvant treatments were retrieved. Fourteen (12.7%) patients had cervical involvement (stage II) according to the surgical pathology report, of whom nine (8.1%) had stage IIA and five (4.6%) had stage IIB. Clinical evaluation by speculoscopy and palpation had failed to reveal any indication of cervical involvement. Preoperative diagnostic hysteroscopy procedures were included. None of the hysteroscopy procedures revealed any suspicious lesion in the cervical canal. Hysteroscopy and clinical examination fail to adequately predict cervical involvement in endometrial carcinoma. Fractional D&C appears to be the best method until a more effective alternative becomes available. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether women with endometrial cancer have a higher incidence of microscopic extrauterine spread in early-stage disease when diagnosed by hysteroscopy compared with being diagnosed by dilatation and curettage (D&C) or endometrial biopsy (Pipelle). We retrospectively reviewed the medical records of 110 patients who had undergone surgical staging for endometrial cancer from January 1997 to December 2003. They all had a preoperative histological diagnosis of endometrial carcinoma without evidence of extrauterine disease. Diagnosis was made by hysteroscopy in 64 patients (58.2%), by D&C in 17 (15.5%), and by endometrial biopsy using a Pipelle device in 29 (26.3%). The groups were compared for known prognostic factors for microscopic extrauterine spread, including age, grade, stage, and vascular space involvement, and did not differ in these parameters. Microscopic intraperitoneal disease and positive peritoneal cytology were considered the primary endpoints of this analysis. Peritoneal cytology was positive in three of 110 (2.7%) patients. The presence of positive peritoneal cytology was not associated with hysteroscopy as the diagnostic procedure. We conclude that diagnosis of endometrial cancer by hysteroscopy does not increase the risk of microscopic intraperitoneal spread compared with diagnosis by D&C or endometrial biopsy (Pipelle). [ABSTRACT FROM AUTHOR]