Is nuchal translucency of 3.0-3.4 mm an indication for cfDNA testing or microarray? - a multicenter retrospective clinical cohort study.

INTRODUCTION: This study aimed to evaluate the occurrence of clinically relevant (sub)microscopic chromosomal aberrations in fetuses with the NT range from 3.0 to 3.4 mm, which would be potentially missed by cfDNA testing. METHODS: A retrospective data analysis of 271 fetuses with NT between 3.0 and 3.4 mm and increased combined test (CT) risk in five cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed. RESULTS: A chromosomal aberration was identified in 18.8% fetuses (1:5; 51/271). In 15% (41/271) of cases trisomy 21, 18, or 13 was found. In 0.7% (2/271) sex chromosome aneuploidy was found. In 1.1% (3/271) of cases, CNV>10Mb was detected, which would potentially also be detected by genome-wide cfDNA testing. The residual risk for missing a submicroscopic chromosome aberration in the presented cohorts is 1.8% (1:54; 5/271). CONCLUSION: Our results indicate that a significant number of fetuses with increased CT risk and presenting NT of 3.0-3.4 mm carry a clinically relevant chromosomal abnormality other than common trisomy. Invasive testing should be offered and counseling on NIPT should include the test limitations that may result in NIPT false negative results in a substantial percentage of fetuses.

NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury.

Retinal ganglion cells (RGCs), neurons transmitting visual information via the optic nerve, fail to regenerate their axons after injury. The progressive loss of RGC function underlies the pathophysiology of glaucoma and other optic neuropathies, often leading to irreversible blindness. Therefore, there is an urgent need to identify the regulators of RGC survival and the regenerative program. In this study, we investigated the role of the family of transcription factors known as nuclear factor of activated T cells (NFAT), which are expressed in the retina; however, their role in RGC survival after injury is unknown. Using the optic nerve crush (ONC) model, widely employed to study optic neuropathies and central nervous system axon injury, we found that NFATc4 is specifically but transiently up-regulated in response to mechanical injury. In the injured retina, NFATc4 immunolocalized primarily to the ganglionic cell layer. Utilizing NFATc4-/- and NFATc3-/- mice, we demonstrated that NFATc4, but not NFATc3, knockout increased RGC survival, improved retina function, and delayed axonal degeneration. Microarray screening data, along with decreased immunostaining of cleaved caspase-3, revealed that NFATc4 knockout was protective against ONC-induced degeneration by suppressing pro-apoptotic signaling. Finally, we used lentiviral-mediated NFATc4 delivery to the retina of NFATc4-/- mice and reversed the pro-survival effect of NFATc4 knockout, conclusively linking the enhanced survival of injured RGCs to NFATc4-dependent mechanisms. In summary, this study is the first to demonstrate that NFATc4 knockout may confer transient RGC neuroprotection and decelerate axonal degeneration after injury, providing a potent therapeutic strategy for optic neuropathies.

Is the leptin/BMI ratio a reliable biomarker for endometriosis?

Background: The aim of this study was to analyze the concentration of leptin in peritoneal fluid and plasma and to assess their role as potential biomarkers in the diagnosis of endometriosis. Materials & methods: Leptin adjusted for BMI (leptin/BMI ratio) was measured using surface plasmon resonance imaging (SPRI) biosensors. Patients with suspected endometriosis were included in the study. Plasma was collected from 70 cases, and peritoneal fluid from 67 cases. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group and a control group (patients without endometriosis). Results: Leptin/BMI ratio in plasma did not differ between women with endometriosis and the control group (0.7159 ± 0.259 vs 0.6992 ± 0.273, p= 0,7988). No significant differences were observed in peritoneal leptin/BMI ratio levels in patients with and without endometriosis (0.6206 ± 0.258 vs 0.6215 ± 0.264, p= 0,9896). Plasma and peritoneal leptin/BMI ratios were significantly lower in women with endometriosis - related primary infertility compared to women with endometriosis without primary infertility (0.640 ± 0.502 vs 0.878 ± 0.623, p < 0.05). The difference was observed in case of primary infertility, but not in terms of the secondary one. No significant differences were noted between leptin/BMI ratio in the proliferative phase and the secretory phase (0.716 ± 0.252 vs 0.697 ± 0.288, p= 0,7785). Conclusion: The results of present study do not support the relevance of leptin concentration determination as a biomarker of the endometriosis. Due to the limited number of samples in the tested group, further studies are needed to confirm its role.

The SPRi determination of cathepsin L and S in plasma and peritoneal fluid of women with endometriosis.

PURPOSE: Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis. MATERIAL AND METHODS: In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor. RESULTS: The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma. CONCLUSIONS: Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis.

The Role of Catestatin in Preeclampsia.

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area.

The Effect of Sex on the Risk of Long-COVID and Cardiovascular Complications in Healthy Patients without Comorbidities: Data from a Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study.

Background: The prevalence of long-COVID (LC) presents a significant challenge to healthcare systems globally. There are still some discrepancies on the role of sex as an independent risk factor of LC complications. Thus, we aimed to determine the differences in clinical and cardiovascular complications between males and females without comorbidities after COVID-19. Methods: Clinical data on the course of the disease with the accompanying symptoms and post-COVID-19 symptoms were compiled from both male and female subjects with a minimum 12-week interval after COVID-19 recovery. Next, the patients were followed for 12 months. ECG, echocardiography, 24 h ECG monitoring, 24 h ambulatory blood pressure monitoring (ABPM), and selected biochemical tests were performed. LC was diagnosed based on the World Health Organization (WHO) definition. To reduce the impact of confounders, i.e., body mass index (BMI) and age, on the results of the study, the nearest neighbour (NN) propensity score matching (PSM) method with a 1:1 ratio was used. Results: The results were obtained following the removal of cases with comorbidities from the database consisting of 1237 males and 2192 females, and PSM of the new database included 886 cases (443 males and 443 females). At both the 3-month and 1-year post-recovery marks, females consistently reported a higher frequency of LC symptoms compared to males (p < 0.001 for both comparisons). Moreover, after 1 year of follow-up, females exhibited a higher prevalence of LC compared to males, with rates of 14% versus 8.3%, respectively (p = 0.013). The symptoms that significantly differed between females and males in the 12-month follow-up were hair loss (5.4 vs. 0.7%, p < 0.001), memory and concentration disturbances (8.4 vs. 4.3%, p = 0.013), and headaches (4.3 vs. 1.4%, p = 0.008). Females presented lower mean arterial pressure (MAP) [89 (83-95) mmHg versus (vs.) 94 (89-100); p < 0.001] and lower pulse pressure (PP) [46 (42-52) mmHg vs. 51 (48-57); p < 0.001] in 24 h ABPM and more elevated heart rates (HRs) in 24 h ECG monitoring as well as arrhythmia (p < 0.001 and p = 0.018, respectively). Males had a higher occurrence of ECG abnormalities such as QRS >= 120 ms, ST-T changes, T inversion, arrhythmia, and QRS fragmentation (27.3% vs. 19.2%; p = 0.004). No significant differences were observed between males and females concerning physical activity levels, stress, fatigue, alcohol consumption, and smoking habits. Conclusions: One year post-COVID-19 recovery, regardless of age and BMI, healthy females more often suffered from LC symptoms than males. They had lower MAP and PP in 24 h ABPM, more often had higher HRs and arrhythmia in 24 h ECG monitoring, and fewer ECG abnormalities than males.

Predictors of Long-COVID and Chronic Impairment of Exercise Tolerance in Spiroergometry in Patients after 15 Months of COVID-19 Recovery.

BACKGROUND: The aim of the study was to identify factors that may cause the presence of long COVID and to assess factors that affect chronic limited exercise tolerance in spiroergometry after one-year follow-up in patients who had recovered from COVID-19. METHODS: Of 146 patients hospitalised in the Cardiology Department, 82 completed a one-year follow-up (at least 15 months post-COVID-19 recovery). We compared their conditions at initial screening and follow-up to analyse the course of long COVID and exercise intolerance mechanisms. Clinical examinations, laboratory tests, echocardiography, cardiopulmonary exercise testing, and body composition analysis were performed. RESULTS: The patients, after one-year follow-up, had significantly higher levels of high-sensitivity cardiac troponin T (hs-cTnT) (p = 0.03), left atrium diameter (LA) (p = 0.03), respiratory exchange ratio (RER) (p = 0.008), and total body water content percentage (TBW%) (p < 0.0001) compared to the 3-month assessment. They also had lower forced vital capacity in litres (FVC) (p = 0.02) and percentage (FVC%) (p = 0.001). The factors independently associated with a decline in maximum oxygen uptake (VO2max) after one-year follow-up included the percentage of fat (OR 2.16, 95% CI: 0.51-0.77; p = 0.03), end-diastolic volume (EDV) (OR 2.38, 95% CI 0.53-0.78; p = 0.02), and end-systolic volume (ESV) (OR 2.3, 95% CI: 0.52-0.78; p = 0.02). CONCLUSIONS: Higher left ventricular volumes and fat content (%) were associated with a reduced peak VO2max when assessed 15 months after COVID-19 recovery.

New Ideas for the Prevention and Treatment of Preeclampsia and Their Molecular Inspirations.

Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.

Effects of the Trp64Arg Polymorphism in the ADRB3 Gene on Body Composition, Cardiorespiratory Fitness, and Physical Activity in Healthy Adults.

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults (N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath-Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference (p = 0.035), hip circumference (p = 0.029), BF (%) (p = 0.008), and BF (kg) (p = 0.010), BMI (p = 0.005), WHtR (p = 0.021), and BAI (p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components (p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake (p= 0.023) and oxygen pulse (p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise (p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise.

Diagnostic Usefulness of Spiroergometry and Risk Factors of Long COVID in Patients with Normal Left Ventricular Ejection Fraction.

The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic has brought forth various clinical manifestations and long-term complications, including a condition known as long COVID. Long COVID refers to a persistent set of symptoms that continue beyond the acute phase of the disease. This study investigated the risk factors and the utility of spiroergometry parameters for diagnosing patients with long COVID symptoms. The 146 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with normal left ventricular ejection fraction and without respiratory diseases were included and divided into two groups: the group demonstrating long COVID symptoms [n = 44] and the group without long COVID symptoms [n = 102]. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. ClinicalTrials.gov Identifier: NCT04828629. Patients with long COVID symptoms had significantly higher age [58 (vs.) 44 years; p < 0.0001], metabolic age [53 vs. 45 years; p = 0.02)], left atrial diameter (LA) [37 vs. 35 mm; p = 0.04], left ventricular mass index (LVMI) [83 vs. 74 g/m2, p = 0.04], left diastolic filling velocity (A) [69 vs. 64 cm/s, p = 0.01], the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') [7.35 vs. 6.05; p = 0.01], and a lower ratio of early to late diastolic transmitral flow velocity (E/A) [1.05 vs. 1.31; p = 0.01] compared to the control group. In cardiopulmonary exercise testing (CPET), long COVID patients presented lower forced vital capacity (FVC) [3.6 vs. 4.3 L; p < 0.0001], maximal oxygen consumption measured during incremental exercise indexed per kilogram (VO2max) [21 vs. 23 mL/min/kg; p = 0.04], respiratory exchange ratio (RER) [1.0 vs. 1.1; p = 0.04], forced expiratory volume in one second (FEV1) [2.90 vs. 3.25 L; p = 0.04], and a higher ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) [106 vs. 100%; p = 0.0002]. The laboratory results pointed out that patients with long COVID symptoms also had a lower rate of red blood cells (RBC) [4.4 vs. 4.6 × 106/uL; p = 0.01]; a higher level of glucose [92 vs. 90 mg/dL; p = 0.03]; a lower glomerular filtration rate (GFR) estimate by Modification of Diet in Renal Disease (MDRD) [88 vs. 95; p = 0.03]; and a higher level of hypersensitive cardiac Troponin T (hs-cTnT) [6.1 vs. 3.9 pg/mL; p = 0.04]. On the multivariate model, only FEV1/FVC% (OR 6.27, 95% CI: 2.64-14.86; p < 0.001) independently predicted the long COVID symptoms. Using the ROC analysis, the FEV1/FVC% ≥ 103 was the most powerful predictor of spiroergometry parameters (0.67 sensitive, 0.71 specific, AUC of 0.73; p < 0.001) in predicting the symptoms of long COVID. Spiroergometry parameters are useful in diagnosing long COVID and differentiating it from cardiovascular disease.

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment.

One of the most dangerous complications of pregnancy is preeclampsia (PE), a disease associated with a high risk of maternal and fetal mortality and morbidity. Although its etiology remains unknown, the placenta is believed to be at the center of ongoing changes. One of the hormones produced by the placenta is chromogranin A (CgA). Thus far, its role in pregnancy and pregnancy-related disorders is enigmatic, yet it is known that both CgA and its derived peptide catestatin (CST) are involved in the majority of the processes that are disturbed in PE, such as blood pressure regulation or apoptosis. Therefore, in this study, the influence of the preeclamptic environment on the production of CgA using two cell lines, HTR-8/SVneo and BeWo, was investigated. Furthermore, the capacity of trophoblastic cells to secrete CST to the environment was tested, as well as the correlation between CST and apoptosis. This study provided the first evidence that CgA and CST proteins are produced by trophoblastic cell lines and that the PE environment has an impact on CST protein production. Furthermore, a strong negative correlation between CST protein level and apoptosis induction was found. Hence, both CgA and its derived peptide CST may play roles in the complex process of PE pathogenesis.

The GLVC scoring system: a single-center model for predicting survival and hospitalization in patients with heart failure.

BACKGROUND: Heart failure (HF) is the only cardiovascular disease with an ever-increasing incidence. AIMS: The aim of this study was to assess the predictors of adverse clinical events (CE) and the creation and evaluation of the prognostic value of a novel personalized scoring system in patients with HF. METHODS: The study included 113 HF patients (median age 64 years (IQR 58-69); 57.52% male). The new novel prognostic score named GLVC (G, global longitudinal peak strain (GLPS); L, left ventricular diastolic diameter (LVDD); V, oxygen pulse (VO2/HR); and C, high sensitivity C-reactive protein (hs-CRP)) was created. The Kaplan-Meier method and log-rank test were used to compare the CE. RESULTS: Results from final analyses showed that low GLPS (< 13.9%, OR = 2.66, 95% CI = 1.01-4.30, p = 0.002), high LVDD (> 56 mm, OR = 2.37, 95% CI = 1.01-5.55, p = 0.045), low oxygen pulse (< 10, OR = 2.8, 95% CI = 1.17-6.70, p = 0.019), and high hs-CRP (> 2.38 µg/ml, OR = 2.93, 95% CI = 1.31-6.54, p = 0.007) were independent prognostic factors for adverse CE in HF population. All the patients were stratified into a low-risk or high-risk group according to a novel "GLVC" scoring system. The Kaplan-Meier analyses demonstrated that patients in the high-risk group were more predisposed to having higher adverse clinical events compared to patients in the low-risk group. CONCLUSIONS: A novel and comprehensive personalized "GLVC" scoring system is an easily available and effective tool for predicting the adverse outcomes in HF.

Two oncomiRs, miR-182-5p and miR-103a-3p, Involved in Intravenous Leiomyomatosis.

Leiomyomas, also referred to as fibroids, belong to the most common type of benign tumors developing in the myometrium of the uterus. Intravenous leiomyomatosis (IVL) tends to be regarded as a rare type of uterine leiomyoma. IVL tumors are characterized by muscle cell masses developing within the uterine and extrauterine venous system. The underlying mechanism responsible for the proliferation of these lesions is still unknown. The aim of the study was to investigate the expression of the two epigenetic factors, oncomiRs miR-182-5p and miR-103a-3p, in intravenous leiomyomatosis. This study was divided into two stages: initially, miR-182-5p and miR-103a-3p expression was assessed in samples coming from intravenous leiomyomatosis localized in myometrium (group I, n = 6), intravenous leiomyomatosis beyond the uterus (group II; n = 5), and the control group, i.e., intramural leiomyomas (group III; n = 9). The expression level of miR-182-5p was significantly higher in samples coming from intravenous leiomyomatosis (group I and group II) as compared to the control group (p = 0.029 and p = 0.024, respectively). In the second part of the study, the expression levels of the studied oncomiRs were compared between seven samples delivered from one woman during a four-year observation. The long-term follow-up of one patient demonstrated significantly elevated levels of both studied oncomiRs in intravenous leiomyomatosis in comparison to intramural leiomyoma samples.

Chromogranin A: An Endocrine Factor of Pregnancy.

Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among others, by the placenta. Although it has been previously linked to pregnancy, no existing articles have ever managed to clarify the role of this protein regarding this subject. Therefore, the aim of the present study is to gather knowledge of chromogranin A's function with reference to gestation and parturition, clarify elusive information, and, most importantly, to formulate hypotheses for the future studies to verify.

Factors of Persistent Limited Exercise Tolerance in Patients after COVID-19 with Normal Left Ventricular Ejection Fraction.

Exercise intolerance de novo is one of the most common reported symptoms in patients recovering from the Coronavirus Disease 2019 (COVID-19). The present study determines etiological and pathophysiological factors influencing the mechanism of impaired exercise tolerance in patients during Long-COVID. Consequently, the factors affecting the percentage predicted oxygen uptake at peak exercise (%VO2pred) in patients after COVID-19 with a normal left ventricular ejection fraction (LVEF) were assessment. A total of 120 patients recovering from COVID-19 at three to six months after confirmed diagnosis were included. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. The subjects were divided into the following groups: study patients' group with worsen oxygen uptake (%VO2pred < 80%; n = 47) and control group presenting%VO2pred ≥ 80% (n = 73). ClinicalTrials.gov Identifier: NCT04828629. The male gender and the percent of total body water content (TBW%) were significantly higher in the study group compared to the control group (53 vs. 29%, p = 0.007 and 52.67 (±6.41) vs. 49.89 (±4.59), p = 0.02; respectively). Patients with %VO2pred < 80% presented significantly lower global peak systolic strain (GLPS), tricuspid annular plane systolic excursion (TAPSE), and late diastolic filling (A) velocity (19.34 (±1.72)% vs. 20.10 (±1.35)%, p = 0.03; 21.86 (±4.53) vs. 24.08 (±3.20) mm, p = 0.002 and median 59.5 (IQR: 50.0−71.0) vs. 70.5 (IQR: 62.0−80.0) cm/s, p = 0.004; respectively) compared to the controls. The results of the multiple logistic regression model show that (A) velocity (OR 0.40, 95%CI: 0.17−0.95; p = 0.03) and male gender (OR 2.52, 95%CI: 1.07−5.91; p = 0.03) were independently associated with %VO2pred. Conclusions: Men have over twice the risk of persistent limited exercise tolerance in Long-COVID than women. The decreased (A) velocity, TAPSE, GLPS, and hydration status are connected with limited exercise tolerance after COVID-19 in patients with normal LVEF.

Reliability of Rodent and Rabbit Models in Preeclampsia Research.

In vivo studies on the pathology of gestation, including preeclampsia, often use small mammals such as rabbits or rodents, i.e., mice, rats, hamsters, and guinea pigs. The key advantage of these animals is their short reproductive cycle; in addition, similar to humans, they also develop a haemochorial placenta and present a similar transformation of maternal spiral arteries. Interestingly, pregnant dams also demonstrate a similar reaction to inflammatory factors and placentally derived antiangiogenic factors, i.e., soluble fms-like tyrosine kinase 1 (sFlt-1) or soluble endoglin-1 (sEng), as preeclamptic women: all animals present an increase in blood pressure and usually proteinuria. These constitute the classical duet that allows for the recognition of preeclampsia. However, the time of initiation of maternal vessel remodelling and the depth of trophoblast invasion differs between rabbits, rodents, and humans. Unfortunately, at present, no known animal replicates a human pregnancy exactly, and hence, the use of rabbit and rodent models is restricted to the investigation of individual aspects of human gestation only. This article compares the process of placentation in rodents, rabbits, and humans, which should be considered when planning experiments on preeclampsia; these aspects might determine the success, or failure, of the study. The report also reviews the rodent and rabbit models used to investigate certain aspects of the pathomechanism of human preeclampsia, especially those related to incorrect trophoblast invasion, placental hypoxia, inflammation, or maternal endothelial dysfunction.

Effects of Implementing Personalized Health Education in Ambulatory Care on Cardiovascular Risk Factors, Compliance and Satisfaction with Treatment.

Aim and Methods: Data from the CARDIOPLUS study (a prospective, multicenter, non-interventional study, which was conducted among patients and physicians from ambulatory patient care in Poland) were used to assess whether primary care behavioral counseling interventions to improve diet, increase physical activity, stop smoking and reduce alcohol consumption improve outcomes associated with cardiovascular (CVD) risk factors, metabolic parameters, compliance and satisfaction with treatment in adults. The study was carried out throughout Poland in the period from July to December 2019. Results: The study included 8667 patients­49% women and 51% men aged (63 ± 11 years)­and 862 physician-researchers. At the 3-month follow-up, there was a significant reduction in body weight (p = 0.008); reduction of peripheral arterial pressure, both systolic (p < 0.001) and diastolic (p < 0.001); reduction in total cholesterol levels (p < 0.001), triglycerides (p < 0.001), and LDL cholesterol (p < 0.001). The percentage of respondents who fully complied with the doctor's recommendations increased significantly. The respondents assessed their own satisfaction with the implemented treatment as higher (by about 20%). Conclusions: As a result of pro-health education in the field of lifestyle modifications, a significant reduction of risk factors for cardiovascular diseases, as well as improved compliance and satisfaction with pharmacological treatment, was observed. Thus, appropriate personalized advice on lifestyle habits should be given to each examinee in a positive, systematic way following the periodic health check-ups in order to reduce the person's risk and improve the effectiveness of the treatment.

Obesity and Body Mass Components Influence Exercise Tolerance and the Course of Hypertension in Perimenopausal Women.

The aim of this study was to identify the potential influence of obesity and body mass components on exercise tolerance assessed in cardiopulmonary exercise testing (CPET), biochemical and echocardiographic parameters and factors correlated with oxygen absorption at the anaerobic threshold in hypertensive women with low levels of physical activity in the perimenopausal period. The study comprised 188 hypertensive women divided, based on body mass index (BMI), into an obesity group and a non-obesity group. Women with BMI ≥ 30 kg/m2 had significantly higher parameters of left ventricular diastolic dysfunction in echocardiography, lower total body water (TBC) in percentage assessed by bioimpedance and significantly worse exercise capacity assessed by CPET. In the study group, VO2 AT (mL/kg/min) correlated positively with TBW (r = 0.4, p < 0.0001) and with the ratio of extracellular water to total body water (ECW/TBW) (r = 0.4, p < 0.00001) and negatively with fat (% and kg) (r = −0.4, p < 0.0001 for both). Obesity negatively affects parameters of diastolic left ventricular function, as well as exercise tolerance in CPET in hypertensive females during the perimenopausal period. The oxygen uptake at anaerobic threshold correlates positively with total body water and ECW/TBW and negatively with body fat; this connection is more pronounced in women without obesity. ClinicalTrials.gov Identifier: NCT04802369.

The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia.

Preeclampsia (PE) is characterised by high levels and activity of the transcription factor Nuclear Factor kappa B (NFĸB) in the maternal blood and placental cells. This factor is responsible for the regulation of over 400 genes known to influence processes related to inflammation, apoptosis and angiogenesis, and cellular responses to oxidative stress and hypoxia. Although high NFĸB activity induces hypoxia and inflammation, which are beneficial for the process of implantation, NFĸB level should be reduced in the later stages of physiological pregnancy to favour maternal immunosuppression and maintain gestation. It is believed that the downregulation of NFĸB activity by pharmacotherapy might be a promising way to treat preeclampsia. Interestingly, many of the drugs adopted for the prevention and treatment of preeclampsia have been found to regulate NFĸB activity. Despite this, further innovation is urgently needed to ensure treatment safety and efficacy. The present article summarizes the current state of knowledge about the drugs recommended by cardiology, obstetrics, and gynaecology societies for the prevention and treatment of preeclampsia with regard to their impact on the cellular regulation of NFĸB pathways.

New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism.

Introduction: Congenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown. Material and methods: Targeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state. Results: Here we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PROKR2/SPRY4/NSMF. These genes are known to contribute to the phenotype of hypogonadotropic hypogonadism, yet our results point to potential new "partners" underlying digenic and trigenic patterns. Conclusions: The finding supports the importance of oligogenic inheritance and demonstrates the complexity of genetic architecture in hypogonadotropic hypogonadism. It also underlines the necessity for developing fine-tuned guidelines to provide a tool for adequate and precise sequence variant classification in non-Mendelian conditions.