Management of late-onset fetal growth restriction: pragmatic approach.

OBJECTIVES: There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. METHODS: This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. RESULTS: Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). CONCLUSIONS: Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Disentangling age-dependent DNA methylation: deterministic, stochastic, and nonlinear.

DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of "deterministic" CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of "stochastic" CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.

[The treatment efficacy of disturbed swallowing function in patients with ischemic stroke and neurogenous dysfagia in the intensive care unit]. / Éffektivnost' lecheniia narushennoi funktsii glotaniia u patsientov s ishemicheskim insul'tom i neirogennoi disfagiei v ramkakh otdeleniia reanimatsii i intensivnoi terapii.

AIM: To evaluate the efficacy of the training method of rehabilitation of patients with neurogenic dysphagia in ischemic stroke carried out with the use of special nutrient mixtures as part of combination therapy. MATERIAL AND METHODS: The study included 65 patients (35 men and 30 women, aged 45 to 80 years) with dysphagia in the acute period of ischemic stroke. Thirty patients were treated with special binding compounds as part of a combination therapy. Thirty-five patients did not use the mixture. The dynamics of the recovery function of swallowing using PAS (the Penetration-Aspiration Scale) and FEDSS (the Fiberoptic Endoscopic Dysphagia Severity Scale), as well as the transition from tube to independent feeding were studied. RESULTS AND CONCLUSION: The training method of rehabilitation with the help of special nutritional mixtures allows achieving significantly better indicators of restoration of swallowing function assessed with PAS and FEDSS in patients with ischemic stroke and neurogenic dysphagia. This trend is most pronounced in the group of patients with pseudobulbar syndrome. The application of the training method leads to a significantly better transition from tube to independent feeding. Tracheal intubation and mechanical ventilation are an additional factor aggravating swallowing disorders.

[A comparative analysis of the results of percutaneous nephrolithotomy and laparoscopic pyelolithotomy].

INTRODUCTION: Percutaneous nephrolithotripsy (PNL) is considered as the main treatment method of patients with large and staghorn kidney stones. In some cases, laparoscopic pyelolithotomy (LP) may be an alternative option to PNL. The aim of our work was to compare the results of these surgical methods for treatment of large pelvis stones. MATERIALS AND METHODS: The results of surgical treatment of 60 patients with large pelvis stones were reviewed. In 40 patients (66.7%) PNL were performed, while in 20 cases (33.3%) LP were done. In the PNL group, the average stone size was 2.7 (2.5-3.8) cm and in the LP group it was 3.0 (2.6-4.2) cm. Four patients in the LP group had kidney malrotation, one patient had pelvic dystopia, and in another case a horseshoe kidney was diagnosed. The operative time and stone-free rate, intra- and postoperative complications, the amount of blood loss and the length of hospitalization were compared. RESULTS: There was no conversion in both groups. There were no significant differences in the mean length of hospitalization (4.5+/-1.5 vs 4.4+/-1.4 days) and analgesic use (2.2+/-0.9 vs 2.4+/-1.0 days) and stone-free rate (100 vs 90%) between groups. The mean operative time was significantly higher at the PL (110.0+/-25.0 vs 65.4+/-24.5 min; p less or equal 0.05), but the amount of blood loss was significantly lower (70+/-28 versus 160.0+/-55 ml; p less or equal 0.05) compared to the PNL group. CONCLUSIONS: PNL remains the main treatment method for patients with large kidney stones. However, abnormal kidneys, concomitant ureteropelvic junction obstruction or endoscopic treatment failure can be indications to LP.

[The infective complications of the percutaneous nephrolithotomy].

In the article the main causes of the development of infective complications after percutaneous nephrolithotomy and their predictors described by the different authors are presented. A review of studies, dedicated to analysis of baseline risk factors of postoperative fever, systemic inflammatory response syndrome and/or sepsis was conducted. It was established that stone size and true bacteriuria are reliable risk factors as well as technical features of PCNL and the duration of the surgery. The staghorn and multiple stones increase the postoperative complications rate by three times. Despite low incidence of postoperative sepsis after PCNL, it is the serious complication and the main cause of mortality in a postoperative period. The use of prophylactic antibiotics with consideration of bacteria, isolated from the urinary tract significantly reduces the incidence of the postoperative infectious complications. The scheme of a single injection of the antibiotic 30 minutes before the surgery is effective.

[Subcapsular renal hematomas after ureteroscopic lithotripsy].

INTRODUCTION: Renal hematomas (RH) are a rare complication of retrograde endoscopic lithotripsy (REL). This study aimed to investigate the incidence and causes of RH after REL in patients with ureteral stones of different locations. MATERIALS AND METHODS: From 2001 to 2016, 1214 REL were performed at the Urology Clinic of the Mechnikov NWSMU. The analyzes of patients who had RH after REL included the following parameters: age, gender, history of upper urinary tract (UUT) surgery and concomitant diseases (diabetes mellitus, hypertension), the baseline kidney function, the stone characteristics and the degree of hydronephrosis observed in the postoperative period, results of laboratory tests, ultrasound and spiral computed tomography (SCT) of the kidneys. RESULTS: Renal hematomas were diagnosed in 4 (0.3%) of 1214 patients aged 36 to 50 years who had obstructive upper ureteral stones measuring from 0.8 to 1.2 cm in diameter. Three of them previously had UUT surgery: two had REL, and one female patient with a solitary left kidney twice underwent percutaneous nephro- and ureterolithotripsy. All four patients had a triad of symptoms: side flank pain, fever, and anemia. In three patients hematomas were diagnosed on day 2-3 and in one it was found two weeks after the surgery. Two of them were managed with conservative therapy, including bed rest and antibiotics. One patient underwent an ultrasound guided puncture and drainage of the hematoma. In the patient with a solitary kidney, laparoscopic drainage of RH was performed due to growing hematoma and aggravating renal insufficiency. Two patients received blood transfusions. Follow-up kidney SCT showed complete resolution of hematomas in all patients. CONCLUSION: Renal hematomas are a rare but serious complication of REL. The presence of side flank pain, fever and anemia may be indicative of REL and requires a kidney ultrasound. Management of RH should be patient specific, depending on the severity of the patients condition.

Sonographers' self-reported visualization of normal postmenopausal ovaries on transvaginal ultrasound is not reliable: results of expert review of archived images from UKCTOCS.

OBJECTIVE: In the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), self-reported visualization rate (VR) of the ovaries by the sonographer on annual transvaginal sonographic (TVS) examinations was a key quality control (QC) metric. The objective of this study was to assess self-reported VR using expert review of a random sample of archived images of TVS examinations from UKCTOCS, and then to develop software for measuring VR automatically. METHODS: A single expert reviewed images archived from 1000 TVS examinations selected randomly from 68 931 TVS scans performed in UKCTOCS between 2008 and 2011 with ovaries reported as 'seen and normal'. Software was developed to identify the exact images used by the sonographer to measure the ovaries. This was achieved by measuring caliper dimensions in the image and matching them to those recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimensions and visualization data reported by the expert. RESULTS: The expert reviewer confirmed visualization of both ovaries (VR-Both) in 50.2% (502/1000) of the examinations. The software identified the measurement image in 534 exams, which were split 2:1:1 providing training, validation and test data. Classifier mean accuracy on validation data was 70.9% (95% CI, 70.0-71.8%). Analysis of test data (133 exams) provided a sensitivity of 90.5% (95% CI, 80.9-95.8%) and specificity of 47.5% (95% CI, 34.5-60.8%) in detecting expert confirmed visualization of both ovaries. CONCLUSIONS: Our results suggest that, in a significant proportion of TVS annual screens, the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude that QC metrics based on self-reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Early detection of cancer in the general population: a blinded case-control study of p53 autoantibodies in colorectal cancer.

BACKGROUND: Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population. METHODS: Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case-control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer. RESULTS: The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9-8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12-3.8) years before clinical diagnosis. CONCLUSION: Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.

Magnetic field and contact resistance dependence of non-local charge imbalance.

Crossed Andreev reflection (CAR) in metallic nanostructures, a possible basis for solid-state electron entangler devices, is usually investigated by detecting non-local voltages in multi-terminal superconductor/normal metal devices. This task is difficult because other subgap processes may mask the effects of CAR. One of these processes is the generation of charge imbalance (CI) and the diffusion of non-equilibrium quasi-particles in the superconductor. Here we demonstrate a characteristic dependence of non-local CI on a magnetic field applied parallel to the superconducting wire, which can be understood by a generalization of the standard description of CI to non-local experiments. These results can be used to distinguish CAR and CI and to extract CI relaxation times in superconducting nanostructures. In addition, we investigate the dependence of non-local CI on the resistance of the injector and detector contacts and demonstrate a quantitative agreement with a recent theory using only material and junction characteristics extracted from separate direct measurements.

Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic "aging mosaic". At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.

Fluctuations of persistent current.

We theoretically analyze equilibrium fluctuations of the persistent current (PC) in nanorings. We demonstrate that these fluctuations persist down to zero temperature provided the current operator does not commute with the total Hamiltonian of the system. For a model of a quantum particle on a ring we explicitly evaluate PC noise power which has the form of sharp peaks at frequencies set by the corresponding interlevel distances. In rings with many conducting channels, a much smoother and broader PC noise spectrum is expected. A specific feature of PC noise is that its spectrum can be tuned by an external magnetic flux indicating the presence of quantum coherence in the system.

[Plasmapheresis intensive therapy of progressing stage of psoriatic disease].

There were examined 124 medical histories of patients with psoriatic disease in progressing stage. It's found that including of hardware-generated filtrational-membrane plasmapheresis, providing a middle-volume exfusion of plasma and following compensation of missing volume by water-electrolytic balanced solution at the beginning of intensive therapy of acute stage of disease is pathogenesisly proved and effective. Advancing using of plasmapheresis is shown on examples of patients with PASI more then 18 points, tending to decreasing of duration of acute form and severity of pathological process.

[The 265th anniversary of Orenburg military hospital].

Orenburg military hospital, founded according to decree of empress Anna Ioanovna one year later after grounding of fortress Orenburg, started it's work in June 1744. To the beginning of the Great Patriotic War 1941-1945 the hospital was a big military treatment institute. In 1946-1958 the hospital was a regional hospital of South-Ural military region, and then--regional hospital of Baikal military region. Hospital takes an active party in life of the Armed Forces in general, it's staff comprises veterans of Afgan war, of other flash points, military servicemen and civil staff taken part in peacemaking operations.

Inherent multistability in arrays of autoinducer coupled genetic oscillators.

Rhythm generation mechanisms are very important for genetic network functions as well as for the design of synthetic genetic circuits. A significant attention to date has been focused on the synchronization of communicating genetic units, which results in the production of an unified rhythm. In contrast to this we address the question: what mechanisms of intercell communication can be responsible for multirhythmicity in globally coupled genetic units? Here, we show that an autoinducer intercell communication system that provides coupling between synthetic genetic oscillators will inherently lead to multirhythmicity and the appearance of several coexisting dynamical regimes, if the time evolution of the genetic network can be split in two well-separated time scales. We investigate in detail a variety of dynamical regimes in a genetic population and show the possibility for multiple element distributions between clusters, as well as the possibility of generating complex oscillations with different return times in one limit cycle.

Stochastic suppression of gene expression oscillators under intercell coupling.

This paper examines the dynamics of an ensemble of hysteresis-based genetic relaxation oscillators, focusing on the influence of noise and cell-to-cell coupling on the appearance of new dynamical regimes. In particular, we show that control of the coupling strength and noise can effectively change the dynamics of the system leading to behaviors such as clustering, synchronous and asynchronous oscillations, and suppression. Moreover, under certain conditions an optimal amount of noise can lead to increased order in the system. The results obtained are correlated with relevant biological processes that occur in living organisms.

Noise-induced inhibitory suppression of frequency-selective stochastic resonance.

We study the control of oscillations in a system of inhibitory coupled noisy excitable and oscillatory units. Using dynamical properties of inhibition, we find regimes when the oscillations can be suppressed but the information signal of a certain frequency can be transmitted through the system. The mechanism of this phenomenon is a resonant interplay of noise and the transmission signal provided by certain value of inhibitory coupling. Analyzing a system of three or four oscillators representing neural clusters, we show that this suppression can be effectively controlled by coupling and noise amplitudes.

Noise-induced excitability in oscillatory media.

A noise-induced phase transition to excitability is reported in oscillatory media with FitzHugh-Nagumo dynamics. This transition takes place via a noise-induced stabilization of a deterministically unstable fixed point of the local dynamics, while the overall phase-space structure of the system is maintained. Spatial coupling is required to prevent oscillations through suppression of fluctuations (via clustering in the case of local coupling). Thus, the joint action of coupling and noise leads to a different type of phase transition and results in a stabilization of the system. The resulting regime is shown to display characteristic traits of excitable media, such as stochastic resonance and wave propagation. This effect thus allows the transmission of signals through an otherwise globally oscillating medium.

Oscillatory amplification of stochastic resonance in excitable systems.

We study systems which combine both oscillatory and excitable properties, and hence intrinsically possess two internal frequencies, responsible for standard spiking and for small amplitude oscillatory limit cycles (Canard orbits). We show that in such a system the effect of stochastic resonance can be amplified by application of an additional high-frequency signal, which is in resonance with the oscillatory frequency. It is important that for this amplification one needs much lower noise intensities as for conventional stochastic resonance in excitable systems.

Doubly stochastic coherence via noise-induced symmetry in bistable neural models.

The generation of coherent dynamics due to noise in an activator-inhibitor system describing bistable neural dynamics is investigated. We show that coherence can be induced in deterministically asymmetric regimes via symmetry restoration by multiplicative noise, together with the action of additive noise which induces jumps between the two stable steady states. The phenomenon is thus doubly stochastic, because both noise sources are necessary. This effect can be understood analytically in the frame of a small-noise expansion and is confirmed experimentally in a nonlinear electronic circuit. Finally, we show that spatial coupling enhances this coherent behavior in a form of system-size coherence resonance.

Frequency-dependent stochastic resonance in inhibitory coupled excitable systems.

We study frequency selectivity in noise-induced subthreshold signal processing in a system with many noise-supported stochastic attractors which are created due to slow variable diffusion between identical excitable elements. Such a coupling provides coexisting of several average periods distinct from that of an isolated oscillator and several phase relations between elements. We show that the response of the coupled elements under different noise levels can be significantly enhanced or reduced by forcing some elements in resonance with these new frequencies which correspond to appropriate phase relations.