Healthy Non-pregnant Women Research Articles

Diminished retinal microcirculation in mild preeclampsia without obvious retinopathy in high-altitude native Tibetans by OCTA

BackgroundTo investigate the retinal microcirculation in mild preeclampsia (PE) without obvious retinopathy in high-altitude native Tibetans by optical coherence tomography angiography (OCTA). MethodsThis study enrolled 64 mild preeclamptic pregnant women without retinopathy (group PPW), 63 healthy pregnant women (group HPW), and 61 healthy non-pregnant women (group HNPW). All participants were high-altitude native Tibetans who underwent OCTA, retinal thickness (RT), vascular density (VD), perfusion density (PD) and foveal avascular zone (FAZ) parameters were measured in the macula. Differences in these parameters among the groups were compared, and the correlations of these parameters with blood pressure were evaluated. ResultsIn the entire macula, VD and PD were significantly lower in group PPW than in group HPW and HNPW (p < 0.05). In the subregions, VD was significantly different in fovea, parafovea and perifovea, PD was significantly different in parafovea and perifovea among the three groups (p < 0.05), the further pairwise comparisons showed VD and PD in parafovea and perifovea were lower in group PPW than in group HPW, and VD and PD in perifovea were lower in group PPW than in group HNPW (p < 0.05). RT and FAZ parameters did not differ among the groups (P > 0.05). VD and PD exhibited negative correlations with SBP and DBP (p < 0.05). ConclusionOCTA can objectively evaluate diminished microcirculation in mild PE without obvious retinopathy among high-altitude native Tibetans, and provide a crucial time window for early screening of PE-induced retinopathy.

Synthesis of cytokines during physiological pregnancy

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy. The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

Expression of Molecules Characterizing Metabolic and Cytotoxic Activity of Natural Killer Different Subpopulations of Peripheral Blood During Pregnancy

The functions of peripheral blood NK cells change significantly during pregnancy, which is mainly due to the inhibition of their cytotoxicity. The functional activity of NK cells is directly related to their metabolic status, but these changes in physiological pregnancy have not been studied. The aim of this work is to study the expression of Glut-1, CD94 and CD107a molecules characterizing metabolic and cytotoxic activity, as well as the mitochondrial mass of different subpopulations of peripheral blood NK cells in the I and III trimesters of physiological pregnancy. The object of the study was the peripheral blood of healthy women in the I and III trimesters of physiological pregnancy. The control group consisted of healthy non-pregnant women in the follicular phase of the menstrual cycle. The expression of Glut-1, CD94, CD107a molecules and the mitochondrial mass were analyzed by flow cytometry on regulatory (CD16–CD56bright), cytotoxic (CD16+CD56dim), minor cytotoxic (CD16hiCD56–) NK cells. It was found that in non-pregnant women, minor cytotoxic CD16hiCD56–NK have the highest expression of Glut-1, CD107a and the lowest expression of CD94 compared to other NK cell subpopulations. On regulatory CD16–CD 56bright and cytotoxic CD16+CD56dimNK, the expression of these molecules is comparable to each other. The mitochondrial mass is similar in all studied subpopulations. In the first trimester, the expression of Glut-1 increases on regulatory CD16–CD56brightNK, the mitochondrial mass and the expression of CD94, CD107a in all NK cells do not differ from non-pregnant ones. In the third trimester, the mitochondrial mass increases in cytotoxic CD16+CD56dimNK cells, but CD94 expression decreases compared to non-pregnant ones, and the expression CD94 in regulatory CD16–CD56brightNK increases compared to the first trimester. CD107a expression in minor cytotoxic CD16hiCD56–NK decreases, but in other subpopulations does not change compared to non-pregnant. The expression of Glut-1 does not change in all subpopulations. Thus, different subpopulations of peripheral blood NK cells are heterogeneous in the expression of Glut-1, CD107a, CD94. The expression of these molecules during physiological pregnancy varies by trimester. The obtained results are important for understanding the mechanisms of NK cell function regulations during pregnancy.

Evaluation of Changes in the Patency of the Nasal Cavity and Eustachian Tube Depending on the Phase of the Menstrual Cycle: A Pilot Study.

(1) Background: Estrogen and progesterone, hormones specific to females, undergo fluctuations during the menstrual cycle. The aim of this study was to assess subjective and objective changes in nasal cavity and Eustachian tube patency depending on the phase of the menstrual cycle in two groups of women: those in a follicular phase group and those in a luteal phase group. (2) Materials and Methods: The study group consisted of 25 healthy non-pregnant women aged 24 to 32. Based on the phase of the cycle confirmed in sonography, they were divided into follicular phase (FP) and luteal phase (LP) groups. The Eustachian tube and nasal cavity patency examination was carried out using a SNOT-22 Questionnaire, a rhinomanometer, and a tympanometer. (3) Results: We observed that the incidence of nasal obstruction in SNOT-22 was significantly dependent on the cycle phase (p = 0.012) and was lower in the FP compared to the LP. Similar relationships were noticed between the cycle phase and the rhinomanometry outcome, where the LP was associated with a lower flow. We also revealed that the incidence of ear blockage significantly depended on the cycle phase (p = 0.001) and was lower in the FP compared to the LP. Women whose nasal patency deteriorated during the LP also had more negative pressure values in tympanometry. We observed that patients with negative PEAK L and R levels had a lower flow in rhinomanometry. (4) Conclusions: The results highlight the menstrual cycle's substantial impact on both subjective and objective nasal and Eustachian tube patency measurements. The novel finding in this study is that women whose nasal patency deteriorated during the luteal phase also had more negative pressure values in tympanometry. These results suggest that the deterioration of hearing during the menstrual cycle could be a result of swelling of the nasal mucosa and tubes.

Evaluation of Regulatory B Cells and Serum IL-10 Concentration in Peripheral Blood of Women with Recurrent Pregnancy Loss

Background: Although the role of B cells in normal pregnancy has been recently highlighted, their importance and function are not completely clarified. Until now, some investigations have shown that during pregnancy, regulatory B cells (Breg), a subset of B cells, are one of the key players in immune regulation by both producing IL-10 and cell-cell interactions. Therefore, any decrease in the number or function of these cells may lead to recurrent pregnancy loss (RPL). Thus, the objective of this study was to characterize Breg cell frequency and function in women who suffered from RPL in comparison with healthy non-pregnant and pregnant women (under twenty weeks of gestational age) as controls. Method: In this study, peripheral blood samples of women suffering from RPL (n=8), women with normal pregnancy under 20 weeks of gestational age (n=14), and healthy nonpregnant women (n=10) were collected. The frequency of Breg cells (CD19+CD24hiCD38hi) was measured by flow cytometry. The serum level of the IL-10 cytokine, as a marker of Breg cell function, was measured by ELISA. Results: The Percentage of Breg cells in women who suffered from RPL was significantly lower than that of women who had normal pregnancies (P=0.0016). The percentages of Breg cells in women who suffered from RPL were also significantly lower than in non-pregnant women (P=0.0001). Furthermore, no significant differences were observed in Breg cell percentages between normal pregnant and non-pregnant women. Evaluation of IL-10 concentration in the serum of women who had participated in this study showed no significant differences between the three groups. Conclusion: Based on our results, the number of Breg cells was significantly lower in RPL women than in healthy non-pregnant and normal-pregnant women, which shows the significance of these cells in the maintenance of normal pregnancy. However, we could not detect significant differences in the serum levels of IL-10, bringing to mind the notion that the beneficial and supportive function of these cells during pregnancy might be independent of IL-10 secretion. by these cells. Thus, screening of Breg cells in women with pregnancy complications, especially RPL, could be helpful for predicting a healthy pregnancy.

Reference Intervals of Renal Function Set Established for Healthy Pregnant Women.

This cross-sectional study aimed to explore the variation trend of renal function for healthy pregnant women at different gestational ages and aimed to establish RIs for renal function set tests according to the trimester of pregnancy. A total of 120 healthy pregnant women and 40 healthy non-pregnant women were enrolled in this study and divided into early trimester (1 - 13 weeks of gestation, n = 40), second trimester (14 - 27 weeks of gestation, n = 40), third trimester (≥ 28 weeks of gestation, n = 40), and a non-pregnant women group (n = 40). Analytes of UA, BUN, Cr, β2-MG, Cys-C, RBP, NAG, CO2, HCY, C1q, and NGAL were measured by using the analytical systems of the Second Xiangya Hospital. The RIs were defined by using non-parametric 95% intervals. The RIs for UA, Cr, β2-MG, NAG, CO2, Hcy, and C1q were established for the first and second trimester group and the third trimester group. There were huge differences after pregnancy. The RIs for BUN were different for the 1 - 13 weeks group and the after 14 weeks group. There were significant differences for NGAL in pregnant and non-pregnant women, but not for Cys-C and RBP. The RIs for renal function tests in pregnant women were established, thus providing clinical reference intervals for the clinicians.

Plasma volume is associated with micronutrient mass but not concentration in healthy US women of reproductive age

BackgroundPlasma transports nutrients and composes more than half of the volume of blood. A few prior studies suggest that plasma volume fluctuations may impact certain micronutrient concentrations. We hypothesized a slight negative correlation between plasma volume and micronutrient biomarkers throughout the menstrual cycle in healthy women of reproductive age (n = 45). MethodsThe study involved three visits during one menstrual cycle where fasting blood samples were taken to measure biomarker concentrations for zinc, copper, magnesium, manganese, iron, ferritin, retinol, and hemoglobin. A bolus dose of indocyanine green (ICG; equivalent to 0.25 mg.kg-1 of body weight) was injected to measure plasma volume. The total circulating micronutrient biomarker mass was calculated using the plasma volume and biomarker concentration. We used Spearman's correlation and fractional polynomial regression techniques to assess the relationship between plasma volume and biomarker concentration and mass. ResultsPlasma volume ranged from 1210 to 3520 mL. During all three visits, the correlation between micronutrient biomarker concentrations and plasma volume ranged from -0.05 to 0.10 (all P > 0.05); However, there was a strong positive correlation between biomarker mass and plasma volume, ranging from 0.26 to 0.95 (all P < 0.05). Five of the eight biomarkers examined (zinc, copper, magnesium, retinol, and hemoglobin) showed a correlation coefficient > 0.70 (P < 0.001) between mass and plasma volume. ConclusionOur findings indicate that biomarker concentrations are maintained across a range of plasma volume, suggesting that plasma volume may not be necessary to interpret micronutrient status in healthy non-pregnant women of reproductive age.

Characteristics of the hemostatic system “P-selectin — von Willebrand factor — metalloprotease ADAMTS13” during childbirth

Introduction. The physiological task of the blood coagulation system during childbirth is to prevent excessive blood loss.Aim: to evaluate the quantitative and qualitative characteristics in the system P-selectin-von Willebrand factor (vWF)-metallo-protease ADAMTS13 during natural and uncomplicated childbirth in women with a physiological pregnancy.Materials and methods. The study included 40 pregnant women without somatic pathology, with a physiologically progressing pregnancy that ended with physiological birth (general group). Of these, 16 women had their first birth (group 1), 18 had their second birth (group 2) and 6 had their third birth (group 3). Venous blood sampling was performed at three points throughout the study: 1st point — the onset of labor, 2nd point — 2 hours after childbirth and 3rd point — 24 hours after child -birth. The control group consisted of 25 healthy non-pregnant women. The blood samples were examined for: vWF antigen (vWF:Ag), binding ability of vWF to platelet receptor GPIb (vWF:GPIb), binding ability of vWF to collagen type I (vWF:CBAI) and type III (vWF:CBAIII), antigen and activity ADAMTS13 (ADAMTS13:Ag and ADAMTS13:AC), antibodies to ADAMTS13 (ADAMTS13:AB) and P-selectin.Results. The medians of the studied vWF characteristics in the genera l group were statistically significantly higher compared to the control group at all study points, with the exception of the medians of the vWF:GPIb/vWF:Ag ratio, which in the general group were statistically significantly lower at all study points when compared with the control group. The median values of vWF:GPIb and vWF:Ag in women in the second group were statistically significantly higher at all points of the study, compared with similar indicators in both the first and third groups. The median values of ADAMTS13:AC and ADAMTS13:AB in the overall group were statistically significantly higher when compared with the control group at all study points. Median ADAMTS13:Ag and ADAMTS13:AC/ADAMTS13:Ag ratios were statistically significantly lower at all study points. Individual P-selectin values varied widely from 212.1 to 1398 ng/ml, but the medians of this indicator were statistically significantly higher in all study groups and at all study points compared to the control group.Conclusion. The increase in platelet-binding and collagen-binding abilities of vWF suggests that these adhesive properties of the hemostatic protein play an important role in preventing excessive bleeding during labor. Taking into account the decrease in the vWF:GPIb/vWF:Ag ratio compared to the control group, the adhesion of vWF to collagen is more important under these conditions. Despite the fact that ADAMTS13 concentration does not decrease, an actual twofold increase in its activity provides a sufficient antithrombotic effect. The interaction between vWF and ADAMTS13 under conditions of physiological labor does not lead to excessive formation and accumulation of high-affinity antibodies to ADAMTS13.

Optical coherence tomography angiography evaluation of retinal and choroidal microvascular changes in pregnant women with a history of unexplained recurrent spontaneous abortions.

To study retinal and choroidal microcirculation by optical coherence tomography angiography (OCTA) in pregnant women with unexplained recurrent spontaneous abortion (RSA) and to compare them with healthy pregnant and nonpregnant subjects. Pregnant women with an unexplained history of RSA (group 1), healthy pregnant (group 2), and healthy non-pregnant women (group 3) were included in the study. After a thorough ophthalmologic examination:best-corrected visual acuity, intraocular pressure,slit-lamp biomicroscopy, fundus examination,autorefractometer, biometry, and axial length measurement; OCT and OCTA measurements were performed with Swept Source OCT-Angiography (Topcon Co, Japan). The nonpregnant group had higher values for central foveal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD) and lower values for superior, inferior, and mean VD compared with pregnant groups (p < 0.001). Choriocapillaris values (CC) VD were higher in groups 1 and 2 than in group 3 (p < 0.001). The group with unexplained RSA had a relatively smaller FAZ (foveal avascular zone) area than the group of healthy pregnant women (p:0.047). There were no statistically significant differences between groups in the retina, retinal nerve fiber layer, ganglion cell layer, and choroidal thickness (p > 0.05). Although our study did not identify any etiology in pregnant women with RSA, we observed detectable differences in FAZ area and vessel density values using OCTA, when comparing them with healthy pregnant women and healthy nonpregnant controls. We believe that OCTA, as used in many pathologies such as diabetic and hypertensive retinopathy and retinal vascular occlusion, can also be extended to unexplained RSA both to detect etiology and to monitor treatment in studies with a larger number of patients.

Фактори ризику аденоміозу в жінок репродуктивного віку

The problem of adenomyosis is of particular relevance to patients of reproductive age since these diseases are accompanied by significant violations of the menstrual and generative functions. Aim - determine the risk factors for the development of adenomyosis in women of reproductive age in order to improve a complex pathogenetically based approach in the selection of treatment. Materials and methods. Analysis of anamnestic data and examination of 90 women of reproductive age with adenomyosis, which made up the main group, was carried out. The control group - 30 gynecologically healthy non-pregnant women of reproductive age. Results. The article provides data on the results of clinical-statistical analysis among reproductive-age women with the adenomyosis. The risk factors of development of adenomyosis in investigated group are determined. Those are: complicated heredity, high frequency of the clinical abortions, spontaneous miscarriages, pathological deliveries in the past. The low index of health is observed in such category of women: high sick rate of gynecological or extragenital pathology, 3 times higher frequency of child's and respiratory illnesses, the surgical intervention on uterus and ovarium promotes the progress of the endometriosis. That the most frequent clinical manifestations of adenomyosis are pain and hemorrhagic syndrome. Conclusions. The clinical and statistical analysis of the examined patients made it possible to identify risk factors for the development of adenomyosis in women of reproductive age: burdened heredity (60%), unmarried and single women (58.5%); employees with intellectual and mental and neuropsychological stress (63.3%), high infection index, accompanying extragenital pathology (37.4%), menstrual cycle disorders (93.3%) and reduced reproductive and sexual function; aggravated gynecological history: chronic inflammatory processes of the uterus and appendages (44.2%), pathology of the cervix (36.5%), artificial (66.6%) and involuntary (14.4%) abortions; intrauterine surgical interventions (76.3%). The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Bleeding Time and Clotting Time in Pre-eclampsia, Eclampsia and Normal Pregnancy

Introduction: The most important cause of maternal and perinatal morbidity and mortality are hypertensive disorder (Preeclampsia and eclampsia). In preeclampsia and eclampsia there is hypercoagulable state which acts as a risk factor for thromboembolism and DIC. Objective: This study was carried out to compare the coagulation indices in normal pregnancy, preeclampsia and eclampsia. Materials and Methods: This cross sectional study was conducted in Dhaka Medical College from January to December’ 2014. Total 150 women aged 18 – 40 years were selected for this study. Among them 50 normal pregnant, 50 preeclamptic and 50 eclamptic women were selected as study group and age matched 50 healthy nonpregnant women were considered as control group. Bleeding time was estimated by Duke’s method and clotting time was estimated by capillary tube method. Results: In this study bleeding time and clotting time were significantly higher in preeclamptic and eclamptic women than those of healthy nonpregnant women. Conclusion: From this study it can be concluded that bleeding time and clotting time are closely related with preeclampsia and eclampsia. Medicine Today 2023 Vol.36 (1): 41-44

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial

There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete. Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. The EU Horizon Program TRACVAC.

Qualitative study on shared decision making in cystitis management in general practice.

Cystitis is commonly treated with antibiotics, although non-antibiotic options could be considered for healthy non-pregnant women. Shared decision making (SDM) can be used in cystitis management to discuss the various treatment options but is not frequently applied in general practice. To identify barriers and facilitators for applying SDM in cystitis management in general practice. Qualitative explorative research in general practice with healthcare professionals (HCPs; GPs and GP assistants) and healthy non-pregnant women with a recent history of cystitis (patients). Individual semi-structured interviews were conducted between May and October 2022. We applied a combination of thematic and framework analysis. Ten GPs, seven GP assistants, and 15 patients were interviewed. We identified the following three main barriers and one key facilitator: (1) applying SDM is deemed inefficient; (2) HCPs assume that patients expect antibiotic treatment and some HCPs consider non-antibiotic treatment inferior; (3) patients are largely unaware of the various non-antibiotic treatment options for cystitis; and (4) HCPs recognise some benefits of applying SDM in cystitis management, including reduced antibiotic use and improved patient empowerment, and patients appreciate involvement in treatment decisions, but preferences for SDM vary. SDM is infrequently applied in cystitis treatment in general practice owing to the current focus on efficient cystitis management that omits patient contact, HCPs' perceptions, and patient unawareness. Nevertheless, both HCPs and patients recognise the long-term benefits of applying SDM in cystitis management. Our findings facilitate the development of tailored interventions to increase the application of SDM, which should be co-created with HCPs and patients, and fit into the current efficient cystitis management.

Evaluation of Fibrinogen Level and Platelet Count among the Apparently Healthy Pregnant Women at 3rd Trimester

Background: Different physiological changes affect normal coagulation and fibrinolytic system during pregnancy. Hemostatic abnormalities are often associated with various complications of pregnancy. Objectives: This study was aimed to evaluate the fibrinogen level and platelet count among pregnant women at third (3rd) trimester as compared to non-pregnant healthy women. Methods: This cross-sectional study was conducted at the Department of Physiology, Rajshahi Medical College (RMC), Rajshahi, Bangladesh, from July 2016 to June 2017 on 60 healthy women, out of them 30 were apparently healthy pregnant women of third trimester in the age group of 20-35 years (cases), and 30 were age matched non-pregnant healthy women (controls). Their detailed case history was taken and relevant clinical examinations were done. Plasma fibrinogen level and platelet count were measured using auto analyzer. Data were analyzed and compared by statistical test. Results: The mean±SD age of the pregnant women was 27.27±3.72 years and that was 27.13±4.01 years in non-pregnant healthy women. The maximum (40.0%) study women were in 26-30 years age group followed by 38.3% was in 20-25 years age group and 21.7% was in 31-35 years age group. Most of the cases were primipara [22(36.66%)] and majority women in the control group were multiparous [17(28.33%)]. Mean±SD body mass index (BMI), pulse rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were nearly similar between the groups. Plasma fibrinogen level was significantly high (p&lt;0.001) and platelet count was relatively low among women at 3rd trimester of pregnancy in comparison to non-pregnant healthy women. Conclusion: Plasma fibrinogen level is significantly high and platelet count is relatively low at 3rd trimester of pregnancy. Coagulation parameters are altered in a balanced way during normal 3rd trimester pregnancy.

Characteristics and functions of memory regulatory T cells in normal pregnancy cycle and pregnancy complications

Regulatory T cells (Tregs) are activated and expanded after exposure to fetal-specific (paternal) antigens. A proportion of Tregs differentiate into memory Tregs (mTregs), exhibiting immune memory function and exerting more potent immunosuppression than naive Tregs (nTregs). However, it is unclear how mTregs are regulated during normal and pathological pregnancies (e.g., gestational diabetes mellitus (GDM) and preeclampsia (PE)). In this study, PD-1, HLA-G, and HLA-DR expressions on memory CD4+ T cells, naive CD4+ T cells, Tregs, mTregs, and nTregs in healthy non-pregnant women (n=20), healthy first (n=20), second (n=20), and third-trimester women (n=20), postpartum women (n=20), GDM (n=20), and PE patients (n=20) were analyzed. The proportion of mTregs out of Tregs was increased (P<0.05) in the first trimester compared with that in non-pregnancy and reduced in the second and third trimesters. The proportions of PD-1+ Tregs and mTregs were significantly increased during the first trimester compared to those of non-pregnancy (P<0.01), reached their maximum in the second trimester. Moreover, the proportions of HLA-G+ memory CD4+ T cells, Tregs, and mTregs were increased in the first and second trimesters (P<0.01), reached their maximum in the third trimester. GDM patients were characterized by significantly lower percentages of PD-1+ and HLA-G+ mTregs (P<0.01), while PE patients were characterized by significantly lower percentages of HLA-G+ mTregs (P<0.01), compared with the healthy third-trimester women. In general, as demonstrated by this study, mTregs increase in number and enhance maternal-fetal immunoregulation during pregnancy, and their dysfunction can result in pregnancy complications such as GMD or PE.

A comparison among oscillometric waveforms in healthy nonpregnant women, pregnancy and hypertensive disorders of pregnancy.

Understanding of how oscillometric waveforms (OMW) vary between pregnant and nonpregnant individuals remains low. An exploratory analysis was completed to assess for quantitative and qualitative changes in OMW and oscillometric envelope features in pregnancy. Eighteen pregnant individuals (over 20 weeks gestational age) and healthy, nonpregnant (HNP) women were recruited. Six HNP were matched to six healthy pregnant (HP) women, and six pregnant women with a hypertensive disorder of pregnancy (HDP) by age, arm circumference, and cuff size. Blood pressure measurements were completed per the International Organization for Standardization (ISO) protocol using a custom-built oscillometric device as the test device and two-observer mercury auscultation as the reference measurement. Auscultatory blood pressure and blood pressure derived from slope-based and fixed ratio algorithms were determined. OMW and envelope features were compared among groups. In HNP, HP, and HDP groups respectively: mean auscultatory blood pressure (systolic mean ± SD/diastolic mean ± SD) was 103.4 ± 12.2/67.1 ± 7.9; 109.5 ± 3.1/58.1 ± 6.4; 135.6 ± 18.9/85.1 ± 14.2 mmHg. HDP had significantly higher auscultatory systolic and diastolic blood pressure than the HP group ( P = 0.001). The pregnant groups had a lower average pulse width (mean ± SD: HNP = 0.8 ± 0 s, HP = 0.6 ± 0.1 s, HDP = 0.6 ± 0.1 s; HP vs. HNP mean difference [adjusted P value]: 0.2 [ P = 0.004], HDP vs. HNP 0.1 [ P = 0.018]) compared with the HNP group. The HDP group had a larger area under the OMW envelope than the HNP group (mean ± SD: HNP = 22.6 ± 3.4; HDP = 28.5 ± 4.2; HDP vs. HNP mean difference [adjusted P value]: 5.9 P = 0.05). In this exploratory work, differences in the OMW morphology and parameters were found in pregnancy and in hypertensive disorders of pregnancy compared with healthy controls. Even small differences may have important implications in algorithm development; further work comparing OMW envelopes in pregnancy is needed to optimize the algorithms used to determine blood pressure in pregnancy.

ICOS-ICOSL pathway enhances NKT-like cell antiviral function in pregnant women with COVID-19.

Objective: The immune response initiated by SARS-CoV-2 infection in pregnancy is poorly elucidated. We aimed to access and compare the antiviral cellular responses and lymphocytes activation between healthy pregnancies and pregnant women infected with SARS-CoV-2. Methods: We detected the immunological changes of lymphocytes in peripheral blood of healthy non-pregnant women, non-pregnant women with COVID-19, healthy pregnant women, pregnant women with COVID-19 and convalescent group by flow cytometry. In vitro blockade was used to identify NKT-like cell activation through ICOS-ICOSL pathway. Results: We found that CD3+CD56+ NKT-like cells decreased significantly in COVID-19 positive pregnant women compared to healthy pregnant women. NKT-like cells of pregnant women expressed higher level of activating receptors CD69 and NKp46 after SARS-CoV-2 infection. Particularly, they also increased the expression of the co-stimulatory molecule ICOS. NKT-like cells of pregnant women with COVID-19 up-regulated the expression of IFN-γ, CD107a and Ki67. Meanwhile, we found that ICOSL expression was significantly increased on pDCs in pregnant women with COVID-19. Blocking ICOS in vitro significantly decreased the antiviral activity of NKT-like cells in COVID-19 positive pregnant women, suggesting that ICOS-ICOSL may play an important role in the virus clearance by NKT-like cells. Conclusions: During SARS-CoV-2 infection, NKT-like cells of pregnant women activated through ICOS-ICOSL pathway and played an important role in the antiviral response.

Comorbid pathology of the mammary glands and endometriosis: risk factors and prognosis

Aim: based on a retrospective analysis, the relationship between external genital endometriosis and comorbid breast pathology was established and risk factors were identified, their comparison and the formation of a prognostic risk criterion were determined. Materials and Methods: to address the objectives of the study, a retrospective analysis of 470 cases of patients treated for external genital endometriosis after surgical treatment and comorbid breast pathology was conducted. The control group included 30 healthy non-pregnant women. Statistical processing was performed on a personal computer using the statistical software package Statistica 10. Results: As a result of the analysis, the age of the patients ranged from 23 to 40 years. The average age of patients in the study group was (32.2}1.18) years, and in the control group (31.1}1.35) (p&gt;0.05). The groups were homogeneous in terms of age (p&gt;0.05), marital status (p&gt;0.05) and level of education (p&gt;0.05). Close relatives in 208 (44.25}2.18) % (OR=8.86; 95 % CI: (0.68-10.53); p&lt;0.002) cases suffered from benign (hormone-dependent) tumours and tumour-like diseases of the uterus and appendages in isolation or in various combinations (fibroids, adenomyosis, endometrial hyperplasia). It was also found that 102 (21.70}1.67) % of patients had endometriosis, which may indicate a genetic predisposition to this disease. In the closest relatives of EM patients: in 118 (25.10}2.01) % of the examined parents, breast problems were noted, in 66 (14.04}1.12) % – diabetes mellitus, and in 98 (20.85}1.22) % thyroid diseases were detected, which in total amounted to (60.00}2.23) % (OR=9.12; 95 % CI: (0.58-11.54); p&lt;0.002). Early menarche almost tripled the risk of EM (OR=2.72; 95% CI: (1.02-5.11); p&lt;0.002), and menstrual irregularities doubled it (OR=2.04; 95% CI: (1.09-3.14); p&lt;0.05), higher education, urban residents – 2.2 times higher (OR= 2.27; 95 % CI: (1.11-3.63); p&lt;0.05), diseases of the gastrointestinal tract and hepatobiliary complex – 5.2 times higher (OR=5.27; 95 % CI: (1.89-12.03); p&lt;0.05), frequently recurrent inflammatory diseases of the appendages – 3 times higher (OR=3.14; 95 % CI: (0.91-5.14); p&lt;0.05), dysmetabolic manifestations (thyroid dysfunction) – 5 times higher (OR=5.11; 95 % CI: (1.61-9.503); p&lt;0.002). Conclusions: Thus, in endometriosis and dyshormonal diseases of the mammary glands, menstrual and generative function disorders, along with clinical symptoms of pelvic pain, dysmenorrhoea, autonomic nervous system disorders and sexual dysfunction, are significant components of this problem, initiating comorbidity processes in target organs in the setting of hormonal maladaptation. Therefore, these comorbidities become a trigger for the activation of systemic hormonal imbalance and become an urgent interdisciplinary problem that requires further study.

Determination of cytokines for assessment of inflammatory status at genital endometriosis

Objective: The Aim of the research was to study the profile of serum cytokines in patients with genital endometriosis, as well as to evaluate the sensitivity and specificity of any single cytokine or combination of cytokines in predicting the inflammatory status in endometriosis.&#x0D; Material and methods: The study included 48 patients. They were divided into two groups: I group (experimental) – 28 women with genital endometriosis, II group (control) - 20 healthy non-pregnant women. For the determination of serum biomarkers (IL-6, IL-8, IL-18, TNF-α, MIF) the multiplex immunofluorescence method with XMap technology was used.&#x0D; Results: There were no statistical differences in IL-18 and MIF levels between the studied groups (p = 0.630 and p = 0.421). However, serum levels of IL-6, IL-8, TNF-α were significantly different (respectively, p = 0.037, p &lt; 0.001, p &lt; 0.001). In women with endometriosis the levels of IL-8 and TNF-α were increased 5 times, and level of IL-6 was increased 3 times. The diagnostic significance of IL-6, IL-8 and TNF-α levels for predicting genital endometriosis was 75.0% and 60.0%; 100.0% and 90.0%; 92.9% and 85.0%, respectively.&#x0D; Conclusions: The levels of IL-6, IL-8, and TNF-α were significantly higher in patients with genital endometriosis. The diagnostic significance of IL-6, IL-8 and TNF-α levels for predicting genital endometriosis was also established with the determination of the sensitivity and specificity of the model.&#x0D; Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 121-129

Serum CYFRA21–1 and SCC-Ag levels in women during pregnancy and their diagnostic value for cervical cancer

ObjectivesThe incidence of cervical cancer increases every year during pregnancy. Cervical cytology in pregnant women has a unique morphology and liquid-based cytology methods are prone to cause false positives. The aim of this study was to investigate the serum cytokeratin 19 fragment antigen 21–1 (CYFRA21–1) and squamous cell carcinoma associated antigen (SCC-Ag) concentrations in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy. MethodsIn this prospective study, 165 healthy non-pregnant women, 441 healthy pregnant women and 22 patients with cervical cancer in pregnancy were recruited. The healthy pregnant women group included 143 women in the first trimester (T1), 147 in the second (T2) and 151 in the third (T3). ResultsBoth SCC-Ag and CYFRA21–1 levels were significantly different in the healthy pregnant women group compared to the control group. The CYFRA21–1 and SCC-Ag were higher in the T1 and T3 than in the control groups. However, there was no statistically significant difference in serum CYFRA21–1 and SCC-Ag levels in the T2 group compared to the control group. The AUCs of CYFRA21–1, SCC-Ag and CYFRA21–1 combined with SCC-Ag were 0.674, 0.792, and 0.805, respectively. The cut-off values of CYFRA21–1 and SCC-Ag were 6.64 ng/mL and 1.75 ng/mL, respectively. ConclusionsSerum CYFRA21–1 and SCC-Ag levels were higher in pregnant women during early and late pregnancy compared to non-pregnant individuals, while they were not statistically different from non-pregnant women during mid-trimester. CYFRA21–1 and SCC-Ag have diagnostic value for cervical cancer in pregnancy.