Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth.

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group's 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Biomechanical Integrity Score of the Female Pelvic Floor for Stress Urinary Incontinence.

INTRODUCTION AND HYPOTHESIS: This study is aimed at developing and validating a new integral parameter, the Biomechanical Integrity score (BI-score) of the female pelvic floor for stress urinary incontinence conditions. METHODS: A total of 130 subjects were included in the observational cohort study; 70 subjects had normal pelvic floor conditions, and 60 subjects had stress urinary incontinence (SUI). A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t test, correlation) to identify the VTI parameters sensitive to the pelvic SUI conditions. RESULTS: Twenty-seven parameters were identified as statistically sensitive to SUI development. They were subdivided into five groups to characterize tissue elasticity (group 1), pelvic support (group 2), pelvic muscle contraction (group 3), involuntary muscle relaxation (group 4), and pelvic muscle mobility (group 5). Every parameter was transformed to its standard deviation units using the dataset for normal pelvic conditions, similar to the T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups 1-5 and to the BI-score in standard deviation units. The p value for the BI-score has p = 4.0 × 10-28 for SUI versus normal conditions. CONCLUSIONS: Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the SUI BI-score in future research and clinical applications.

How the immune mousetrap works: Structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein.

One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization. It has also been suggested that this mechanism is used by influenza A virus in NS1-mediated immunosuppression. We have shown that the peptide corresponding to the primary structure of the potential immunosuppressive domain of NS1 protein (G51) can reduce concanavalin A-induced proliferation of PBMC cells, as well as in vitro, G51 can affect the oligomerization of the core peptide corresponding to the intramembrane domain of TCR, using AFM and small-angle neutron scattering. The results obtained using in cellulo and in vitro model systems suggest the presence of functional interaction between the NS1 fragment and the intramembrane domain of the TCR alpha subunit. We have proposed a possible scheme for such interaction obtained by computer modeling. This suggests the existence of another NS1-mediated mechanism of immunosuppression in influenza.

Maternal Influenza and Offspring Neurodevelopment.

This review examines the complex interactions between maternal influenza infection, the immune system, and the neurodevelopment of the offspring. It highlights the importance of high-quality studies to clarify the association between maternal exposure to the virus and neuropsychiatric disorders in the offspring. Additionally, it emphasizes that the development of accurate animal models is vital for studying the impact of infectious diseases during pregnancy and identifying potential therapeutic targets. By drawing attention to the complex nature of these interactions, this review underscores the need for ongoing research to improve the understanding and outcomes for pregnant women and their offspring.

Variability of internal standard method calibration factors estimated with a multifactorial Taguchi experiment in the analysis of alcoholic products by gas chromatography with flame ionization detection.

This study compares the variability of relative response factors (RRFs) using Taguchi's multifactorial analysis for two internal standard (IS) methods in gas chromatography (GC) for quality control of alcoholic products. Methods where either ethanol or pentan-1-ol was used as an IS were compared. For ten volatile substances prescribed by legislation, the RRFs of both methods were compared under 27 different experimental conditions. The influence of parameters (control factors) such as ethanol content in the matrix, analyte concentration, injected volume, injector temperature, split ratio, and flame ionization detector temperature was evaluated. The selected control factors had values at one of the three levels to cover the commonly used ranges of their settings in the measuring system and to characterize the majority of alcoholic products commonly analyzed in practice. The obtained results showed that the biggest differences in the variability of the results between the two methods were found for the most strictly controlled substances in alcoholic products, acetaldehyde, and methanol, where the application of ethanol as an IS provides clearly better results. For both methods, the way control factors affect the repeatability of GC measurements expressed in the form of relative deviation was also evaluated.

H+-Selective Electrodes Based on Amine-Type Ionophores: Generalized Theory and A Priori Quantification of Lower and Upper Detection Limits.

A critical analysis of the known theories of functioning of H+-selective electrodes (H+-SEs) based on neutral amine-type carriers is given. A model of specific ion association is proposed, according to which, in membranes plasticized with 2-nitrophenyloctyl ether, the protonated ionophore and cation-exchanger form much stronger ion pairs with inorganic ions extracted from the sample solution than with each other, and simple equations that describe the lower and upper limit detection (pHUDL and pHLDL) are obtained. A feasible and reliable method for quantifying the pKa values of ionophores in the membrane phase from potentiometric data is substantiated. The efficiency of using single-ion partition coefficients and ion pair formation constants for a priori quantitative description of the H+-SE response in solutions of various compositions has been demonstrated for the first time. It is shown that the width of the dynamic response range of such electrodes depends on the nature of the tertiary amino group, and the reasons for the observed effect are discussed.

Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle.

To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture.

A feasible, fast and reliable method for estimating ion-site association constants in plasticized PVC ion-selective electrode membranes.

A feasible, fast and reliable method for estimating ion association constants in PVC plasticized membranes of ion-selective electrodes from potentiometric data has been theoretically and experimentally substantiated. The method is based on the established fact of complete dissociation of salts of quaternary ammonium cations R4N + An‒ (except for those containing methyl substituents at the nitrogen atom) in a membrane plasticized with o-nitrophenyl octyl ether (o-NPOE). Therefore, the boundary potential at the interface of the membrane with an aqueous solution of R4N+ depends only upon the concentrations of the corresponding solution and the ion exchanger in the membrane and is independent of the presence of a lipophilic ionic additive (LIA), which makes it possible to use such ions as reference ones in the internal filling solution. If the ions studied (i+) are capable of forming ion associates with the ion exchanger, then the introduction of LIA into the membrane will lead to a decrease in the concentration of free i+ ions and to a corresponding increase in the boundary potential, from which the ion association constant can be directly calculated. The results obtained agree with the known literature data and the results of quantum chemical calculations. The prospective of applying the proposed method to the study of other membrane compositions is discussed.

Determination of Single-Ion Partition Coefficients between Water and Plasticized PVC Membrane Using Equilibrium-Based Techniques.

An experimentally simple method for the direct determination of single-ion partition coefficients between water and a PVC membrane plasticized with o-NPOE is suggested. The method uses the traditional assumption of equal single-ion partition coefficients for some reference cation and anion, in this case tetraphenylphosphonium (TPP+) and tetraphenylborate (TPB-). The method is based on an integrated approach, including direct study of some salts' distribution between water and membrane phases, estimation of ion association constants, and measurements of unbiased selectivity coefficients for ions of interest, including the reference ones. The knowledge of distribution coefficients together with ion association constants allows for direct calculation of the multiple of the single-ion partition coefficients for the corresponding cation and anion, while the knowledge of unbiased selectivity coefficients together with ion association constants allows for immediate estimation of the single-ion partition coefficients for any ion under study, if the corresponding value for the reference ion is known. Both potentiometric and extraction studies are inherently equilibrium-based techniques, while traditionally accepted methods such as voltammetry and diffusion are kinetical. The inner coherent scale of single-ion partition coefficients between water and membrane phases was constructed.

Caught red handed: modeling and confirmation of the myeloperoxidase ceruloplasmin alpha-thrombin complex.

The work is devoted to the study of the structural characteristics of the myeloperoxidase-ceruloplasmin-thrombin complex using small-angle neutron scattering methods in combination with computer modeling, as well as surface plasmon resonance and solid-phase enzyme assay. We have previously shown that the functioning of active myeloperoxidase during inflammation, despite the presence in the blood of an excess of ceruloplasmin which inhibits its activity, is possible due to the partial proteolysis of ceruloplasmin by thrombin. In this study, the myeloperoxidase-ceruloplasmin-thrombin heterohexamer was obtained in vitro. The building of a heterohexamer full-atomic model in silico, considering the glycosylation of the constituent proteins, confirmed the absence of steric barriers for the formation of protein-protein contacts. It was shown that the partial proteolysis of ceruloplasmin does not affect its ability to bind to myeloperoxidase, and a structural model of the heterohexamer was obtained using the small-angle neutron scattering method.

Evaluation of the variation in relative response factors of GC-MS analysis with the internal standard methods: Application for the alcoholic products quality control.

This paper focuses on the evaluation of variation of relative response factors (RRFs) obtained by two internal standard (IS) methods that are used to control the quality of alcoholic products. A standard IS method using 1-pentanol was compared with an "Ethanol as IS" method. The variation of RRF values for both methods was determined using standard solutions based on 20, 40 and 96% ethanol-water matrices. For this purpose, solutions of the ten most abundant volatile compounds were analysed at four different concentrations (250, 500, 1000 and 5000 mg L-1 absolute alcohol, AA) within these matrices. Each solution was measured four times by gas chromatography-mass spectrometry (GC-MS) in single ion monitoring (SIM) mode under repeatability conditions. Our results showed that for the 40% and 96% matrices, the ethanol and standard IS methods showed similar relative standard deviations (RSDs) variation of no more than 2% within the 250-1000 mg L-1 AA volatile compounds concentration range. For the 20% matrix as well as for the 250-5000 mg L-1 AA concentration range the resulting variation in calibration factors reaches 10% for both methods. As for the whole range of 20-96% alcohol by volume (ABV) and 250-5000 mg L-1 AA volatile concentration range, the resultant RRFs for the standard IS method (8% RSD) were more stable than those for the ethanol IS method (almost 40% RSD). Nonlinearity of the signal-to-amount dependence was also assessed with respect to the injection and detection processes.

Biomechanical integrity score of the female pelvic floor.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to develop and validate a new integral parameter, the Biomechanical Integrity score (BI-score), for the characterization of the female pelvic floor. METHODS: A total of 253 subjects with normal and pelvic organ prolapse (POP) conditions were included in the multi-site observational, case-control study; 125 subjects had normal pelvic floor conditions, and 128 subjects had POP stage II or higher. A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t-test, correlation) to identify the VTI parameters sensitive to the pelvic conditions. RESULTS: Twenty-six parameters were identified as statistically sensitive to POP development. They were subdivided into five groups to characterize (1) tissue elasticity, (2) pelvic support, (3) pelvic muscle contraction, (4) involuntary muscle relaxation, and (5) pelvic muscle mobility. Every parameter was transformed to its standard deviation units against the patient age similar to T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups (1)-(5) and the BI-score in standard deviation units. The p-value for the BI-score has p = 4.3 × 10-31 for POP versus normal conditions. A reference BI-score curve against age for normal pelvic floor conditions was defined. CONCLUSIONS: Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the BI-score in future research and practical applications.

Gaucher disease type 1: the first experience of enzyme replacement therapy in pediatric practice in Moldova - case report.

We report on a case of a little girl patient diagnosed with Gaucher disease (GD) type 1 in her early childhood and our first experience with enzyme replacement therapy (ERT). She was first diagnosed accidentally with enlarged spleen during a pediatric examination when she was three years old, but the family ignored investigations; she was hospitalized for diagnosis at six years old. The GD was confirmed based on: clinical manifestations of left abdominal flank pain, multiple bruising, general weakness, bone pain, low appetite, failure to thrive <5th percentile, minor hepato- and severe splenomegaly, enlarged submaxillary lymph nodes, associated by anemia with normal platelets; low activity of beta-Glucosidase, two found mutations in GBA gene, Gaucher cells in bone marrow. The ERT was initiated with Imiglucerase (54 UI/kg/2 wks) two years later after diagnosis, avoiding the splenectomy. Subsequently, the platelets showed the first a promising result, gradually increasing their number every 2 weeks and maintaining it in good parameters till the reported moment (2.5 yrs from the start). The hemoglobin level was appreciated within normal ranges 3 months after ERT start and stabilized completely after 6 months. On the other hand, the red blood count normalized within 20 months of applied therapy. The Lyso-GL-1 decreased by 30% after three months of therapy, no antibodies to Imiglucerase were found. The initial spleen volume (1178.19 cm3) decreased by almost 60% in 6 months of ERT, reaching absolutely normal dimensions after 9 months. The ERT with Imiglucerase was tolerated very well by the patient, showing a clear improvement of clinical symptoms after 4-6 months of therapy, hematological picture and splenomegaly solving. Even if the little patient had to come every 2 weeks for infusion, her quality of life improved a lot, being a totally happy child, going to school and having friends. The ERT should be initiated immediately after diagnosis to prevent the multisystem complications.

Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity.

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.

An approach for security evaluation and certification of a complete quantum communication system.

Although quantum communication systems are being deployed on a global scale, their realistic security certification is not yet available. Here we present a security evaluation and improvement protocol for complete quantum communication systems. The protocol subdivides a system by defining seven system implementation sub-layers based on a hierarchical order of information flow; then it categorises the known system implementation imperfections by hardness of protection and practical risk. Next, an initial analysis report lists all potential loopholes in its quantum-optical part. It is followed by interactions with the system manufacturer, testing and patching most loopholes, and re-assessing their status. Our protocol has been applied on multiple commercial quantum key distribution systems to improve their security. A detailed description of our methodology is presented with the example of a subcarrier-wave system. Our protocol is a step towards future security evaluation and security certification standards.

Formation and Evaluation of a Two-Phase Polymer System in Human Plasma as a Method for Extracellular Nanovesicle Isolation.

The aim of the study was to explore the polyethylene glycol-dextran two-phase polymer system formed in human plasma to isolate the exosome-enriched fraction of plasma extracellular nanovesicles (ENVs). Systematic analysis was performed to determine the optimal combination of the polymer mixture parameters (molecular mass and concentration) that resulted in phase separation. The separated phases were analyzed by nanoparticle tracking analysis and Raman spectroscopy. The isolated vesicles were characterized by atomic force microscopy and dot blotting. In conclusion, the protein and microRNA contents of the isolated ENVs were assayed by flow cytometry and by reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR), respectively. The presented results revealed the applicability of a new method for plasma ENV isolation and further analysis with a diagnostic purpose.

Tactile and Ultrasound Image Fusion for Functional Assessment of the Female Pelvic Floor.

Introduction: The true etiology of pelvic organ prolapse and urinary incontinence and variations observed among individuals are not entirely understood. Tactile (stress) and ultrasound (anatomy, strain) image fusion may furnish new insights into the female pelvic floor conditions. This study aimed to explore imaging performance and clinical value of vaginal tactile and ultrasound image fusion for characterization of the female pelvic floor. Methods: A novel probe with 96 tactile and 192 ultrasound transducers was designed. Women scheduled for a urogynecological visit were considered eligible for enrollment to observational study. Intravaginal tactile and ultrasound images were acquired for vaginal wall deformations at probe insertion, elevation, rotation, Valsalva maneuver, voluntary contractions, involuntary relaxation, and reflex pelvic muscle contractions. Biomechanical mapping has included tactile/ultrasound imaging and functional imaging. Results: Twenty women were successfully studied with the probe. Tactile and ultrasound images for tissues deformation as well as functional images were recorded. Tactile (stress) and ultrasound (strain) images allowed creation of stress-strain maps for the tissues of interest in absolute scale. Functional images allowed identification of active pelvic structures and their biomechanical characterization (anatomical measurements, contractive mobility and strength). Fusion of the modalities has allowed recognition and characterization of levator ani muscles (pubococcygeal, puborectal, iliococcygeal), perineum, urethral and anorectal complexes critical in prolapse and/or incontinence development. Conclusions: Vaginal tactile and ultrasound image fusion provides unique data for biomechanical characterization of the female pelvic floor. Bringing novel biomechanical characterization for critical soft tissues/structures may provide extended scientific knowledge and improve clinical practice.

Predictive Value of Biomechanical Mapping for Pelvic Organ Prolapse Surgery.

OBJECTIVE: This study examined biomechanical changes in pelvic floor after urogynecological surgery. METHODS: This multisite clinical study was designed to explore changes in tissue elasticity, pelvic support, and certain functions (contractive strength, muscle relaxation speed, muscle motility) after pelvic organ prolapse (POP) surgery. A biomechanical mapping of the pelvic floor was performed before and 4 to 6 months after the surgery. The biomechanical data for 52 parameters were acquired by vaginal tactile imaging for manually applied deflection pressures to vaginal walls and pelvic muscle contractions. The two-sample t-test (P < 0.05) was used to test the null hypothesis that presurgery data in group 1 (positive parameter change after surgery) and presurgery data in group 2 (negative parameter change after surgery) belonged to the same distribution. RESULTS: A total of 78 subjects with 255 surgical procedures were analyzed across 5 participating clinical sites. All 52 t-tests for group 1 versus group 2 had P value in the range from 4.0 × 10-10 to 4.3 × 10-2 associating all of the 52 parameter changes after surgery with the presurgical conditions. The P value of before and after surgery correlation ranged from 3.7 × 10-18 to 1.6 × 10-2 for 50 of 52 tests, with Pearson correlation coefficient ranging from -0.79 to -0.27. Thus, vaginal tactile imaging parameters strongly correlated weak pelvic floor presurgery with the positive POP surgery outcome of improved biomechanical properties. CONCLUSIONS: Pelvic organ prolapse surgery, in general, improves the biomechanical conditions and integrity of the weak pelvic floor. The proposed biomechanical parameters can predict changes resulting from POP surgery.

Advanced GC-MS method for quality and safety control of alcoholic products.

Recently developed and validated simple and reliable quantitative method employing ethanol as an internal standard (IS) for GC-MS quantification of volatile compounds in alcoholic products was applied to 36 samples including commercially available world-famous brand spirits from 18 countries and homemade distillates. The GC-MS analyses were performed simultaneously by the suggested approach and official IS method that is prescribed in the legislation of EU and USA. The independent samples t-test was employed to evaluate the statistical difference between the results of these two methods. The test revealed no difference in the results and their repeatability. The main benefits of the suggested method are the elimination of the necessity of manual IS addition and samples density measurement thus making it more economical and productive.