Electromagnetic field (50 Hz) enhance metabolic potential and induce adaptive/reprogramming response mediated by the increase of N6-methyladenosine RNA methylation in adipose-derived mesenchymal stem cells in vitro.

BACKGROUND: Electromagnetic fields (EMF) have an impact on numerous cellular processes. It can positively and negatively affect adipose-derived stem cells (ASCs) thus their fate through the influence of specific factors and protein secretion. EMF can be a great factor for preconditioning ASCs for regenerative medicine purposes, however, understanding the cell's biological response to its effects in vitro is essential. METHODS: ASCs were exposed to the EMF (50 Hz; 1.5 mT) for 24 and 48 h, and then cell biological response was analyzed. RESULTS: 24 h exposure of ASCs to EMF, significantly increased N6-methyladenosine (m6A) RNA methylation, indicating epitranscriptomic changes as an important factor in ASCs preconditioning. Furthermore, the expression of stem cell markers such as Nanog, Oct-4, Sox-2, CD44, and CD105 increased after 24 h of EMF exposure. Besides, western blot analysis showed upregulation of p21 and DNMT2/TRDMT1 protein levels compared to control cells with no differences in the p53 profile. Moreover, after 24 h of exposure to EMF, cell membrane flexibility, the metabolic potential of cells as well as the distribution, morphology, and metabolism of mitochondria were altered. CONCLUSION: ASCs undergo a process of mobilization and adaptation under the EMF influence through the increased m6A RNA modifications. These conditions may "force" ASCs to redefine their stem cell fate mediated by RNA-modifying enzymes and alter their reprogramming decision of as differentiation begins.

Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach.

Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible.

The Dynamic(s) of Adipose Stem Cell System, Their Survival, and Cessation under the Influence of Electromagnetic Fields.

CONTEXT: The electromagnetic field (EMF) is one of the external biophysical factors that can influence stem cells' structure and functionality. Depending on its frequency and magnetic flux density, EMF can have both a positive and negative effect on stem cell biology. AIMS: The aim of the study is to define EMF conditions that support beneficial physiological processes and those that lead to pathophysiological phenomena. Understanding the changes and processes occurring in stem cells after exposure to EMFs of different parameters can be an important factor to be applied in stem cell-based therapies and regenerative medicine. MATERIALS AND METHODS: In this study, using fluorescent microscopy and flow cytometry methods, the influence of EMF on adipose-derived stem cells proliferation, cell cycle, viability, and death were examined. EMF parameters were set in accordance with the ion cyclotron resonance (ICR) theory that influences Ca2+ and Mg2+ ions influx. Results were statistically developed using the ANOVA and effect size (Cohen's d) analyses. RESULTS: In this study, the continuous exposure of adipose-derived stem cells to EMF (ICR parameters: 76.6 Hz; 20 µT) causes a statistically significant increase in cell death through the enhancement of apoptotic, necrotic, and autophagic cell numbers. Apart from increased cell deaths after EMF exposure, increased proliferation after 24 h of EMF exposure has been also observed. CONCLUSIONS: Results presented in this study show that EMF influences stem cell dynamics resulting in a significantly increased cell death, thus altering the stem cell fate. It is important to further establish EMF conditions that support ASCs functioning and beneficial physiological processes for future regenerative medical purposes.

In search of nano-materials with enhanced secondary electron emission for radiation detectors.

There has been limited research devoted to secondary electron emission (SEE) from nano-materials using rapid and heavy ion bombardment. Here we report a comparison of SEE properties between novel nano-materials with a three-dimensional nano-structure composed of a mostly regular pattern of rods and gold used as a standard material for SEE under bombardment of heavy ions at energies of a few MeV/nucleon. The nano-structured materials show enhanced SEE properties when compared with gold. Results from this work will enable the development of new radiation detectors for science and industry.

Augmented deep learning model for improved quantitative accuracy of MR-based PET attenuation correction in PSMA PET-MRI prostate imaging.

PURPOSE: Estimation of accurate attenuation maps for whole-body positron emission tomography (PET) imaging in simultaneous PET-MRI systems is a challenging problem as it affects the quantitative nature of the modality. In this study, we aimed to improve the accuracy of estimated attenuation maps from MRI Dixon contrast images by training an augmented generative adversarial network (GANs) in a supervised manner. We augmented the GANs by perturbing the non-linear deformation field during image registration between MRI and the ground truth CT images. METHODS: We acquired the CT and the corresponding PET-MR images for a cohort of 28 prostate cancer patients. Data from 18 patients (2160 slices and later augmented to 270,000 slices) was used for training the GANs and others for validation. We calculated the error in bone and soft tissue regions for the AC µ-maps and the reconstructed PET images. RESULTS: For quantitative analysis, we use the average relative absolute errors and validate the proposed technique on 10 patients. The DL-based MR methods generated the pseudo-CT AC µ-maps with an accuracy of 4.5% more than standard MR-based techniques. Particularly, the proposed method demonstrates improved accuracy in the pelvic regions without affecting the uptake values. The lowest error of the AC µ-map in the pelvic region was 1.9% for µ-mapGAN + aug compared with 6.4% for µ-mapdixon, 5.9% for µ-mapdixon + bone, 2.1% for µ-mapU-Net and 2.0% for µ-mapU-Net + aug. For the reconstructed PET images, the lowest error was 2.2% for PETGAN + aug compared with 10.3% for PETdixon, 8.7% for PETdixon + bone, 2.6% for PETU-Net and 2.4% for PETU-Net + aug.. CONCLUSION: The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated µ-map and consequently the PET quantification compared to the state of the art.

Value of liver iron concentration in healthy volunteers assessed by MRI.

Iron overload is a relatively common clinical condition resulting from disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, and myelodysplasia that can lead to progressive fibrosis and eventually cirrhosis of the liver. Therefore, it is essential to recognize the disease process at the earliest stage. Liver biopsy is the reference test for the assessment of liver fibrosis. It also allows for quantifying liver iron concentration (LIC) in patients. However, this is an invasive method with significant limitations and possible risks. Magnetic resonance imaging (MRI) and evaluation of the R2* relaxation rate can be an alternative to biopsy for assessing LIC. However, it causes a need for accurate R2* data corresponding to standard value for further comparison with examined patients. This study aimed to assess the normative values of liver R2* in healthy individuals. A total of 100 volunteers that met established criteria were enrolled in the study: 36 (36%) men and 64 (64%) women. The mean age was 22.9 years (range 20 to 32 years). R2* was estimated by an MRI exam with a 1.5 T clinical magnetic resonance scanner. Images for measuring the LIC and liver fat concentration were obtained using the IDEAL-IQ technique for liver imaging. The Mean (SD) liver R2* was 28.34 (2.25) s-1 (95% CI, 27.78-28.90, range 23.67-33.00 s-1) in females, 29.57 (3.20) s-1 (95% CI, 28.49-30.66, range 23.93-37.77 s-1) in males, and 28.72 (2.69) s-1 (range 23.67-37.77 s-1) in the whole group. R2* value in this particular population with a high proportion of young women did not exceed 38 s-1. In the absence of fibrosis or steatosis, liver stiffness and fat fraction did not show any relationship with R2*.

Publisher Correction: Classification of aggressive and classic mantle cell lymphomas using synchrotron Fourier Transform Infrared microspectroscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Uterine leiomyomas: correlation between histologic composition and stiffness via magnetic resonance elastography - a Pilot Study.

OBJECTIVES: To evaluate magnetic resonance elastography as a tool for characterizing uterine leimyomas. MATERIAL AND METHODS: At total of 12 women with symptomatic leiomyomas diagnosed in physical and ultrasound examinations were enrolled in this pilot study. Before surgery, all patients underwent magnetic resonance elastography of the uterus using a 1.5 T MR whole-body scanner (Optima, GE Healthcare, Milwaukee, WI, USA). Surgical specimens were forwarded for histological examination. The findings were allocated into 3 categories depending on the percentage content of connective tissue: below 15%, from 15 to 30% and more than 30%. The median stiffness of leiomyomas for each of the group was calculated. The U-Mann Whitney test was used for statistical analysis. RESULTS: The stiffness of the leiomyomas ranged between 3.7-6.9 kPa (median value 4.9 kPa). The concentration of extracellular components in the leiomyomas did not exceed 40%. An increasing trend of the stiffness with the growing percentage of extracellular component was observed. Stiffness of the leiomyomas obtained by MRE varies depending on microscopic composition. CONCLUSIONS: The value of stiffness shows a trend of increasing with the percentage of extracellular component of the leiomyoma. Further studies are required to assess the usefulness of MRE in diagnostics of uterine leiomyomas.

Classification of aggressive and classic mantle cell lymphomas using synchrotron Fourier Transform Infrared microspectroscopy.

Mantle cell lymphoma (MCL) is regarded as an incurable neoplasm, even to the novel drug strategies. It is known MCL has two morphological variants- classic and aggressive. Aggressive MCL is characterized by a higher mitotic index and proliferation rate, and poor overall survival in comparison to classic subtype. The insight into the detailed biochemical composition of MCL is crucial in the further development of diagnostic and treatment guidelines for MCL patients; therefore Synchrotron radiation Fourier Transform Infrared (S-FTIR) microspectroscopy combined with Principal Component Analysis (PCA) was used. The major spectral differences were observed in proteins and nucleic acids content, revealing a classification scheme of classic and aggressive MCLs. The results obtained suggest that FTIR microspectroscopy has reflected the histopathological discrimination of both MCL subtypes.

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension.

Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously shown that IL-1 receptor antagonist (IL-1Ra) protects against murine BPD; therefore, we hypothesized that IL-1Ra may also be effective against BPD-PH. We employed daily injections of IL-1Ra in a murine model in which BPD/BPD-PH was induced by antenatal LPS and postnatal hyperoxia of 65% O2. Pups reared in hyperoxia for 28 days exhibited a BPD-PH-like disease accompanied by significant changes in pulmonary vascular morphology: micro-CT revealed an 84% reduction in small vessels (4-5 µm diameter) compared to room air controls; this change was prevented by IL-1Ra. Pulmonary vascular resistance, assessed at day 28 of life by echocardiography using the inversely-related surrogate marker time-to-peak-velocity/right ventricular ejection time (TPV/RVET), increased in hyperoxic mice (0.27 compared to 0.32 in air controls), and fell significantly with daily IL-1Ra treatment (0.31). Importantly, in vivo cine-angiography revealed that this protection afforded by IL-1Ra treatment for 28 days is maintained at day 60 of life. Despite an increased abundance of mediators of pulmonary angiogenesis in day 5 lung lysates, namely vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1), no difference was detected in ex vivo pulmonary vascular reactivity between air and hyperoxia mice as measured in precision cut lung slices, or by immunohistochemistry in alpha-smooth muscle actin (α-SMA) and endothelin receptor type-A (ETA) at day 28. Further, on day 28 of life we observed cardiac fibrosis by Sirius Red staining, which was accompanied by an increase in mRNA expression of galectin-3 and CCL2 (chemokine (C-C motif) ligand 2) in whole hearts of hyperoxic pups, which improved with IL-1Ra. In summary, our findings suggest that daily administration of the anti-inflammatory IL-1Ra prevents the increase in pulmonary vascular resistance and the pulmonary dysangiogenesis of murine BPD-PH, thus pointing to IL-1Ra as a promising candidate for the treatment of both BPD and BPD-PH.

Normative values for magnetic resonance elastography-based liver stiffness in a healthy population.

INTRODUCTION Chronic liver disease resulting in fibrosis, and ultimately cirrhosis, is a significant cause of morbidity and mortality worldwide. None of the conventional imaging techniques are able to detect early fibrosis and compare its grade with the histopathologic scale. Liver biopsy, as the diagnostic standard for liver fibrosis, also has limitations and is not well accepted by patients. Magnetic resonance elastography is a well­established technique for evaluating liver stiffness and may replace invasive procedures. Detection of liver fibrosis in its early stages, however, requires a detailed knowledge of normal liver stiffness. OBJECTIVES This study aimed to determine normal liver stiffness values in healthy volunteers. PATIENTS AND METHODS A total of 102 volunteers (mean age, 21.6 years; range, 20-28 years) with no history of gastrointestinal, hepatobiliary, or cardiovascular disease were enrolled in the study. Liver stiffness was evaluated by magnetic resonance elastography with a 1.5T clinical magnetic resonance scanner. Images of the induced transverse wave propagation were obtained and converted to tissue stiffness maps (elastograms). RESULTS The mean (SD) liver stiffness for the entire group of volunteers was 2.14 (0.28) kPa (range, 1.37-2.66 kPa). For women, the mean (SD) stiffness value was 2.14 (0.30) kPa (range, 1.37-2.66 kPa), and for men, 2.14 (0.25) kPa (range, 1.54-2.54 kPa). CONCLUSIONS Liver stiffness in a healthy adult cohort did not exceed 2.7 kPa and is not influenced by sex, body mass index, or fat content.

High-Resolution X-Ray Phase-Contrast 3-D Imaging of Breast Tissue Specimens as a Possible Adjunct to Histopathology.

Histopathological analysis is the current gold standard in breast cancer diagnosis and management, however, as imaging technology improves, the amount of potential diagnostic information that may be demonstrable radiologically should also increase. We aimed to evaluate the potential clinical usefulness of 3-D phase-contrast micro-computed tomography (micro-CT) imaging at high spatial resolutions as an adjunct to conventional histological microscopy. Ten breast tissue specimens, 2 mm in diameter, were scanned at the SYRMEP beamline of the Elettra Synchrotron using the propagation-based phase-contrast micro-tomography method. We obtained pixel size images, which were analyzed and compared with corresponding histological sections examined under light microscopy. To evaluate the effect of spatial resolution on breast cancer diagnosis, scans with four different pixel sizes were also performed. Our comparative analysis revealed that high-resolution images can enable, at a near-histological level, detailed architectural assessment of tissue that may permit increased breast cancer diagnostic sensitivity and specificity when compared with current imaging practices. The potential clinical applications of this method are also discussed.

Does fine-needle aspiration biopsy still have a place in the diagnosis of breast lesions?

INTRODUCTION: Core needle biopsy is a preferable breast biopsy technique under ultrasound guidance. However, fine-needle biopsy is considered equally popular. AIM OF THE STUDY: To redefine the role of fine-needle aspiration biopsy (FNAB) in the diagnosis of breast lesions. MATERIAL AND METHODS: We retrospectively analysed the medical records of 680 patients who underwent breast ultrasound examination. In most cases, no pathologic structures were observed within the mammary glands. In 321 patients, the presence of focal lesions was revealed, and 107 patients in this group qualified for FNAB according to current recommendations. Patients with suspicious smears were referred for core needle or surgical biopsy. Patients with benign cytological smears underwent repeated ultrasound checks at 6-month intervals during the following year. RESULTS: All the smears were diagnostic. The vast majority of the results were categorised as benign lesions. Cancer cells were detected in six women. In one patient the lesion was classified as suspicious, probably malignant. In all of these cases, open biopsy was performed, and histopathological examination confirmed the presence of a malignant tumour. The patients were given appropriate oncological treatment. For women with benign or suspicious, but probably benign, lesions, breast ultrasound was performed twice at six-month intervals. Control tests showed no significant changes compared to the baseline examination. None of the patients required extensive additional diagnostic tests. CONCLUSIONS: FNAB is a reliable method of assessing pathologic lesions in mammary glands.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer.

Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

How electromagnetic fields can influence adult stem cells: positive and negative impacts.

The electromagnetic field (EMF) has a great impact on our body. It has been successfully used in physiotherapy for the treatment of bone disorders and osteoarthritis, as well as for cartilage regeneration or pain reduction. Recently, EMFs have also been applied in in vitro experiments on cell/stem cell cultures. Stem cells reside in almost all tissues within the human body, where they exhibit various potential. These cells are of great importance because they control homeostasis, regeneration, and healing. Nevertheless, stem cells when become cancer stem cells, may influence the pathological condition. In this article we review the current knowledge on the effects of EMFs on human adult stem cell biology, such as proliferation, the cell cycle, or differentiation. We present the characteristics of the EMFs used in miscellaneous assays. Most research has so far been performed during osteogenic and chondrogenic differentiation of mesenchymal stem cells. It has been demonstrated that the effects of EMF stimulation depend on the intensity and frequency of the EMF and the time of exposure to it. However, other factors may affect these processes, such as growth factors, reactive oxygen species, and so forth. Exploration of this research area may enhance the development of EMF-based technologies used in medical applications and thereby improve stem cell-based therapy and tissue engineering.

Application of Raman Spectroscopy and Infrared Spectroscopy in the Identification of Breast Cancer.

Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact verifies that Raman spectroscopy and IR spectroscopy are very useful diagnostic tools that will shed new light in understanding the etiology of breast cancer.

Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis, an autosomal recessive disorder caused by a mutation in a gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), remains a leading cause of childhood respiratory morbidity and mortality. The respiratory consequences of cystic fibrosis include the generation of thick, tenacious mucus that impairs lung clearance, predisposing the individual to repeated and persistent infections, progressive lung damage and shortened lifespan. Currently there is no cure for cystic fibrosis. With this in mind, we investigated the ability of human amnion epithelial cells (hAECs) to express functional CFTR. We found that hAECs formed 3-dimensional structures and expressed the CFTR gene and protein after culture in Small Airway Growth Medium (SAGM). We also observed a polarized CFTR distribution on the membrane of hAECs cultured in SAGM, similar to that observed in polarized airway cells in vivo. Further, hAECs induced to express CFTR possessed functional iodide/chloride (I(-/)Cl(-)) ion channels that were inhibited by the CFTR-inhibitor CFTR-172, indicating the presence of functional CFTR ion channels. These data suggest that hAECs may be a promising source for the development of a cellular therapy for cystic fibrosis.

DNA damage and repair kinetics after microbeam radiation therapy emulation in living cells using monoenergetic synchrotron X-ray microbeams.

A novel synchrotron-based approach, known as microbeam radiation therapy (MRT), currently shows considerable promise in increased tumour control and reduced normal tissue damage compared with conventional radiotherapy. Different microbeam widths and separations were investigated using a controlled cell culture system and monoenergetic (5.35 keV) synchrotron X-rays in order to gain further insight into the underlying cellular response to MRT. DNA damage and repair was measured using fluorescent antibodies against phosphorylated histone H2AX, which also allowed us to verify the exact location of the microbeam path. Beam dimensions that reproduced promising MRT strategies were used to identify useful methods to study the underpinnings of MRT. These studies include the investigation of different spatial configurations on bystander effects. γH2AX foci number were robustly induced in directly hit cells and considerable DNA double-strand break repair occurred by 12 h post-10 Gy irradiation; however, many cells had some γH2AX foci at the 12 h time point. γH2AX foci at later time points did not directly correspond with the targeted regions suggesting cell movement or bystander effects as a potential mechanism for MRT effectiveness. Partial irradiation of single nuclei was also investigated and in most cases γH2AX foci were not observed outside the field of irradiation within 1 h after irradiation indicating very little chromatin movement in this time frame. These studies contribute to the understanding of the fundamental radiation biology relating to the MRT response, a potential new therapy for cancer patients.

Haemodynamic indices of the early phase of the tilt test: does measurement predict outcome?

INTRODUCTION: Tilt testing (TT) is a well-established tool in the diagnosis of syncope. However, it is time-consuming. Therefore, identification of parameters that could shorten the duration of TT is desirable. AIM: To identify and assess the usefulness of early haemodynamic parameter changes in prediction of the tilt test results in a group of patients with syncope of unknown aetiology. METHODS: The study involved a group of 105 patients, including 61 women and 44 men, with a mean age of 34.2+/-13.7 (from 13 to 82) years, with at least two episodes of syncope in the last 6 months. The head-up tilt test was carried out according to protocol 60/20 min and if necessary was continued after administration of sublingual nitroglycerine in a dose of 250 g. The assessment of haemodynamic indices was performed employing the beat-to-beat method using the Portapres M2 device. Systolic (SBP) and diastolic (DBP) arterial pressure, heart rate (HR), cardiac output (CO) and stroke volume (SV), and total peripheral vascular resistance (TPR) were analysed. The measured values of haemodynamic indices were calculated by means of averaging 10-second intervals within 3-minute studied periods either before or after tilting a patient. Mean baroreceptor sensitivity (BRS) for the same 3-minute-long intervals was evaluated using the xBRS (cross-correlation) method. In the analysis, differences (Rx) of the haemodynamic values between the beginning of tilting a patient and the rest period were also calculated. RESULTS: Loss of consciousness was noted in 47 (46%) of the studied patients - group I. The remaining subjects (58 patients, 54%) did not develop syncope during TT (group II). The univariate and multivariate logistic analyses of regression revealed that the mean vascular resistance difference (meanRTPR) <-10 dyn.s/cm8 was an independent risk factor of syncope (chi2=3.4; p<0.0008). The presence of this risk factor was associated with a significantly higher risk of a positive response during the tilt test (65% vs 39%; RR: 1.7, 95% CI: 1.2-3.2). In predicting a positive TT result, sensitivity of this parameter was 65%, specificity was 61% and the prognostic value of the positive and negative result was 32% and 86%, respectively. CONCLUSIONS: In patients with syncope of unknown origin, an early (within first 3 minutes of TT) asymptomatic fall in total peripheral vascular resistance is a significant predictor of a positive final result of the test.