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.

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.

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.

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.

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.

Feasibility and safety of antepartum tactile imaging.

INTRODUCTION AND HYPOTHESIS: Quantitative characterization of the birth canal and critical structures before delivery may provide risk assessment for maternal birth injury. The objective of this study was to explore imaging capability of an antepartum tactile imaging (ATI) probe. METHODS: Twenty randomly selected women older than 21 years with completed 35th week of pregnancy and a premise of vaginal delivery were enrolled in the feasibility study. The biomechanical data were acquired using the ATI probe with a double-curved surface, shaped according to the fetal skull and equipped with 168 tactile sensors and an electromagnetic motion tracking sensor. Software package COMSOL Multiphysics was used for finite element modeling. Subjects were asked for assessment of pain and comfort levels experienced during the ATI examination. RESULTS: All 20 nulliparous women were successfully examined with the ATI. Mean age was 27.8 ± 4.1 years, BMI 30.7 ± 5.8, and week of pregnancy 38.8 ± 1.4. Biomechanical mapping with the ATI allowed real-time observation of the probe location, applied load to the vaginal walls, and a 3D tactile image composition. The nonlinear finite element model describing the stress-strain relationship of the pelvic tissue was developed and used for calculation of Young's modulus (E). Average perineal elastic modulus was 11.1 ± 4.3 kPa, levator ani 4.8 ± 2.4 kPa, and symphysis-perineum distance was 30.1 ± 6.9 mm. The pain assessment level for the ATI examination was 2.1 ± 0.8 (scale 1-4); the comfort level was 2.05 ± 0.69 (scale 1-3). CONCLUSIONS: The antepartum examination with the ATI probe allowed measurement of the tissue elasticity and anatomical distances. The pain level was low and the comfort level was comparable with manual palpation.

Changing times: Fluorescence-lifetime analysis of amyloidogenic SF-IAPP fusion protein.

In a number of conformational diseases, intracellular accumulation of proteins bearing non-native conformations occurs. The search for compounds that are capable of hindering the formation and accumulation of toxic protein aggregates and fibrils is an urgent task. Present fluorescent methods of fibrils' detection prevent simple real-time observations. We suppose to use green fluorescent protein fused with target protein and fluorescence lifetime measurement technique for this purpose. The recombinant proteins analyzed were produced in E. coli. Mass spectrometry was used for the primary structure of the recombinant proteins and post-translational modifications identification. The fluorescence lifetime of the superfolder green fluorescent protein (SF) and the SF protein fused with islet amyloid polypeptide (SF-IAPP) were studied in polyacrylamide gel using Fluorescent-Lifetime Imaging Microscopy (FLIM). It was shown that the SF average fluorescence lifetime in gel slightly differs from that of the SF-IAPP monomer under these conditions. SF-IAPP does not lose the ability to form amyloid-like fibrils. Under the same conditions (in polyacrylamide gel), SF and SF-IAPP monomers have similar fluorescence time characteristics and the average fluorescence lifetime of SF-IAPP in fibrils significantly decreases. We propose the application of FLIM to the measurement of average fluorescence lifetimes of fusion proteins (amyloidogenic protein-SF) in the context of studies using cellular models of conformational diseases.

Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization.

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lactalbumin (bAl), and human lactoferrin (hLf) were investigated using small-angle neutron scattering (SANS). It was shown that while alpha-lactalbumin protein complexes were formed on the surface of polydisperse OA micelles, the lactoferrin complexes comprised a monodisperse system of nanoscale particles. Both hAl and hLf complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization. The possible roles of these processes in the specific anti-tumor activity of these complexes are discussed.

Controlling single-photon detector ID210 with bright light.

We experimentally demonstrate that a single-photon detector ID210 commercially available from ID Quantique is vulnerable to blinding and can be fully controlled by bright illumination. In quantum key distribution, this vulnerability can be exploited by an eavesdropper to perform a faked-state attack giving her full knowledge of the key without being noticed. We consider the attack on standard BB84 protocol and a subcarrier-wave scheme and outline a possible countermeasure.

An Interface Equilibria-Triggered Time-Dependent Diffusion Model of the Boundary Potential and Its Application for the Numerical Simulation of the Ion-Selective Electrode Response in Real Systems.

A simple dynamic model of the phase boundary potential of ion-selective electrodes is presented. The model is based on the calculations of the concentration profiles of the components in membrane and sample solution phases by means of the finite difference method. The fundamental idea behind the discussed model is that the concentration gradients in both membrane and sample solution phases determine only the diffusion of the components inside the corresponding phases but not the transfer across the interface. The transfer of the components across the interface at any time is determined by the corresponding local interphase equilibria. According to the presented model, each new calculation cycle begins with the correction of the components' concentrations in the near-boundary (first) layers of the membrane and solution, based on the constants of the interphase equilibria and the concentrations established at a given time as a result of diffusion. The corrected concentrations of the components in the boundary layers indicate the start of a new cycle every time with respect to the calculations of diffusion processes inside each phase from the first layer to the second one, and so on. In contrast to the well-known Morf's model, the above-mentioned layers do not comprise an imaginary part and are entirely localized in the corresponding phases, and this allows performing the calculations of the equilibrium concentrations by taking into account material balance for each component. The model remains operational for any realistic scenarios of the electrode functioning. The efficiency and predictive ability of the proposed model are confirmed by comparing the results of calculations with the experimental data on the dynamics of the potential change of a picrate-selective electrode in nitrate solutions when determining the selectivity coefficients using the methods recommended by IUPAC.

Objective Differences in Colonoscopy Technique Between Trainee and Expert Endoscopists Using the Colonoscopy Force Monitor.

BACKGROUND: Learning to perform colonoscopy safely and effectively is central to gastroenterology fellowship programs. The application of force to the colonoscope is an important part of colonoscopy technique. AIMS: We compared force application during colonoscopy between novice and expert endoscopists using a novel device to determine differences in colonoscopy technique. METHODS: This is an observational cohort study designed to compare force application during colonoscopy between novice and experienced trainees, made up of gastroenterology fellows from two training programs, and expert endoscopists from both academic and private practice settings. RESULTS: Force recordings were obtained for 257 colonoscopies by 37 endoscopists, 21 of whom were trainees. Experts used higher average forward forces during insertion compared to all trainees and significantly less clockwise torque compared to novice trainees. CONCLUSIONS: We present significant, objective differences in colonoscopy technique between novice trainees, experienced trainees, and expert endoscopists. These findings suggest that the colonoscopy force monitor is an objective tool for measuring proficiency in colonoscopy. Furthermore, the device may be used as a teaching tool in training and continued medical education programs.

Characterizing female pelvic floor conditions by tactile imaging.

INTRODUCTION AND HYPOTHESIS: Tactile imaging (TI) is the high-definition pressure mapping technology which allows recording pressure patterns from vaginal walls under applied load and during pelvic floor muscle contraction. The objective of this study was to identify new tactile imaging and muscle contraction markers to characterize female pelvic floor conditions. METHODS: The study subjects included 22 women with normal and prolapse conditions. They were examined by a new vaginal tactile imaging probe that images the entire vagina, the pelvic floor support structures, and pelvic floor muscle contractions. RESULTS: We identified 11 parameters as potential markers to characterize the female pelvic floor conditions. These parameters correlate with prolapse conditions, patient age, and parity. CONCLUSIONS: Our findings suggest that the tactile imaging markers such as pressure, pressure gradient, and dynamic pressure response during muscle contraction may be used for further quantitative characterization of female pelvic floor conditions.

Improved separate solution method for determination of low selectivity coefficients.

Simple, fast, and theoretically substantiated experimental method for determination of improved selectivity coefficients is proposed. The method is based on the well-known fact that low selectivity coefficients determined by the separate solution method (SSM) are time-dependent and, upon our finding, this dependence is a well-defined linear function of time raised to the certain negative power. In particular, the selectivity coefficients obtained for equally charged primary and foreign ions by SSM linearly depend on time to the minus one-fourth. It was found that extrapolation of experimental data using this function to the intersection with Y axes gives reliable values of rather low selectivity coefficients (down to n × 10(-7)), which strongly differ from those measured using SSM and correspond well with the values obtained using the modified separate solution method (MSSM) proposed by Bakker. At the same time, the new method is free of one very essential limitation inherent to MSSM, namely, it is applicable after the conditioning of electrodes in the primary ion solution and can be repeated many times.

Effect of propofol anesthesia on force application during colonoscopy.

BACKGROUND: Sedation is frequently used during colonoscopy to control patient discomfort and pain. Propofol is associated with a deeper level of sedation than is a combination of a narcotic and sedative hypnotic and, therefore, may be associated with an increase in force applied to the colonoscope to advance and withdraw the instrument. OBJECTIVE: To compare force application to the colonoscope insertion tube during propofol anesthesia and moderate sedation. DESIGN: An observational cohort study of 13 expert and 12 trainee endoscopists performing colonoscopy in 114 patients. Forces were measured by using the colonoscopy force monitor, which is a wireless, handheld device that attaches to the insertion tube of the colonoscope. SETTING: Community ambulatory surgery center and academic gastroenterology training programs. PATIENTS: Patients undergoing routine screening or diagnostic colonoscopy with complete segment force recordings. MAIN OUTCOME MEASUREMENTS: Axial and radial forces and examination time. RESULTS: Axial and radial forces increase and examination time decreases significantly when propofol is used as the method of anesthesia. LIMITATIONS: Small study, observational design, nonrandomized distribution of sedation type and experience level, different instrument type and effect of prototype device on insertion tube manipulation. CONCLUSIONS: Propofol sedation is associated with a decrease in examination time and an increase in axial and radial forces used to advance the colonoscope.

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.

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.

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.

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.

Quantifying vaginal tissue elasticity under normal and prolapse conditions by tactile imaging.

INTRODUCTION AND HYPOTHESIS: Vaginal tactile imaging (VTI) is based on principles similar to those of manual palpation. The objective of this study is to assess the clinical suitability of new approach for imaging and tissue elasticity quantification under normal and prolapse conditions. METHODS: The study subjects included 31 women with normal and prolapse conditions. The tissue elasticity (Young's modulus) was calculated from spatial gradients in the resulting 3-D tactile images. RESULTS: Average values for tissue elasticity for the anterior and posterior compartments for normal conditions were 7.4 ± 4.3 kPa and 6.2 ± 3.1 kPa respectively. For Stage III prolapse the average values for tissue elasticity for anterior and posterior compartments were 1.8 ± 0.7 kPa and 1.8 ± 0.5 kPa respectively. CONCLUSIONS: VTI may serve as a means for 3-D imaging of the vagina and a quantitative assessment of vaginal tissue elasticity, providing important information for furthering our understanding of pelvic organ prolapse and surgical treatment.