Irreversible Changes Research Articles

Exposure to elevated cholesterol results in a non-reversible epigenetic and metabolic shift in macrophages associated with increased residual inflammatory risk

Abstract Almost all patients with or at high risk of atherosclerosis are treated with statin therapy. However, there remains a high burden of cardiovascular risk in these patients. Indeed, it is now clear that residual inflammatory risk is a stronger predictor of cardiovascular events, cardiovascular death, and all-cause death than residual cholesterol risk (as measured by low-density lipoprotein cholesterol). Therefore, in this study we sought to better understand the origin of inflammatory residual risk associated with previous exposure to high cholesterol. Tissue resident macrophages and bone marrow derived macrophages (BMDM) from mice which have been exposed to high cholesterol display an augmented polarisation profile. BMDM’s generated ex vivo are grown under standard condition so any effects come from in vivo exposure to high cholesterol. BMDMs from high cholesterol mice display a heighten M1 and blunted M2-like phenotype. Metabolomic analysis of M(IL-4) macrophages reveal they have breaks in the TCA cycle resulting in reduced capacity to utilise OxPhos which is needed for full M(IL-4) polarisation. Macrophages from chimeric mice generated by bone marrow transfer of high cholesterol bone marrow into irradiated normo-cholesterol mice retain the same phenotype as macrophages from high-cholesterol mice. Critically we demonstrate that there are genome wide irreversible epigenetic changes in bone marrow cells and tissue resident macrophages as a result of exposure to high cholesterol. Mice from a high cholesterol background have an increased number of total HSC (lin-ckit+sca1+) within the bone marrow, however, there is a decreased in the total number of long term (LT)-HSC; critically, this phenotype is not reversible when lipids levels are normalised using monoclonal antibody therapy against PCSK9. This is coupled with an irreversible myeloid skewing in the bone marrow immune cell composition. Newly recruited macrophages within the adipose also retain a heighten M1 and blunted M2-like phenotype despite lipid normalisation conferring a negative systemic metabolic phenotype. Critically, these data show that cholesterol induces long term epigenetic and metabolic changes to HSC and macrophages, which may account for residual inflammatory risk.

Pre‐Vegetation Mixed (Wave‐Tide) Energy Trangressive Nearshore Sedimentation: Evidence From the Proterozoic Passive Margin Sequence of NW Himalaya, India

ABSTRACTThe coupled evolution of the Earth's atmosphere–biosphere system through time has caused irreversible changes in the geodynamics as well as surface processes and sedimentation patterns. One such significant change took place in sedimentation in the Palaeozoic (i.e., Silurian) by the appearance of vascular vegetation. While the impact of evolving vegetation on the terrestrial fluvial environment has been relatively well documented, vegetation‐induced effects down the system in marginal or nearshore marine settings have undergone little study. The Meso‐ to Neoproterozoic Rautgara Formation exposed in the Himalayan Orogenic Belt of NW India, offers a chance to study a well‐preserved fluvial–marine transition to nearshore sedimentation before the appearance of vascular vegetation. A detailed sedimentological analysis identifies six genetically linked facies associations (FA) probably deposited in barrier, back‐barrier, and subtidal deltaic environments. Contrary to the other transgressive barrier models (where beach‐barrier overlie the back barrier environments), in the present case, wave‐dominated barrier deposits mostly occupy the basal part of the stratigraphy. In the middle stratigraphic level, back‐barrier deposits lack thick mud flats and show a dominance of sandstone over mudstone. Stacked subtidal sand bar facies association represents the top part of the sequence. Two sequence stratigraphic surfaces, that is, subaerial unconformity and maximum flooding surface, have been identified and the whole succession is interpreted in terms of HST and TST. Barrier and back‐barrier sediments are deposited during HST and TST, respectively. Subtidal deltaic system developed in late TST. The lack of frequent interbedding between the barrier and back‐barrier facies indicates negligible landward migration of the barrier and demonstrates system stability. The barrier system might have resulted from vertical aggradations akin to modern vegetated systems. The study portrays that sandy barrier systems are common in the Proterozoic. Vegetation and thick mud flats are not always essential for the stability of a barrier‐beach system.

Chronic polypharmacy, monotherapy, and deprescribing: Understanding complex effects on the hepatic proteome of aging mice.

Polypharmacy (use of ≥5 concurrent medications) is highly prevalent among older adults to manage chronic diseases and is linked to adverse geriatric outcomes, including physical and cognitive functional impairments, falls, frailty, hospitalization, and mortality. Deprescribing (withdrawal) is a potential strategy to manage polypharmacy. The broad molecular changes by which polypharmacy causes harm and deprescribing may be beneficial are unknown and unfeasible to study rigorously in tissue from geriatric patients. Therefore, in a randomized controlled trial, we administered therapeutic doses of commonly used chronic medications (oxycodone, oxybutynin, citalopram, simvastatin, or metoprolol) as monotherapy or concurrently (polypharmacy) from middle-age (12 months) to old-age (26 months) to male C57BL/6J (B6) mice and deprescribed (gradually withdrew) treatments in a subset from age 21 months. We compared drug-related hepatic effects by applying proteomics along with transcriptomics and histology. We found that monotherapy effects on hepatic proteomics were limited but significant changes were seen with polypharmacy (93% unique to polypharmacy). Polypharmacy altered the hepatic expression of proteins involved in immunity, and in drug, cholesterol, and amino acid metabolism, accompanied by higher serum drug levels than monotherapies. Deprescribing not only reversed some effects but also caused irreversible and novel changes in the hepatic proteome. Furthermore, our study identified several hepatic protein co-expressed modules that are associated with clinically relevant adverse geriatric outcomes, such as mobility, frailty, and activities of daily living. This study highlights the complex molecular changes following aging, chronic polypharmacy, and deprescribing. Further exploration of these mechanistic pathways may inform management of polypharmacy and deprescribing in older adults.

Intermittent Exercise and Cigarette Smoke Extract-Induced Pulmonary Tensegrity Dysfunction; Monitoring Elastin, Matrix Metalloproteinase-12, Transforming Growth Factor-beta 1

Background: Cigarette smoke causes inflammation of the alveoli, leading to airflow restriction and potentially irreversible changes in lung architecture, including pulmonary emphysema. This study investigates the effects of a six-week aerobic interval training regimen on elastin activity in a rat model of cigarette smoke-induced COPD (CS-COPD). Objectives: Specifically, we observe the variables matrix metalloproteinase-12 (MMP12) and transforming growth factor-beta (TGF-β1). Methods: Twenty male Wistar rats, aged eight weeks, were divided into four groups (n = 5 per group): Control, aerobic interval training (Exe), cigarette smoke extract (CSE), and CSE + Exe. The aerobic interval training (Exe) was performed for 49 min/day, five days per week for six weeks in interval form. The CSE group received an intraperitoneal (IP) injection of 150 µL of cigarette smoke extract, one day per week for six weeks. Results: The CSE and CSE + Exe groups showed a significant decrease in elastin gene expression in lung tissue compared to the healthy control group (P = 0.0002 and P = 0.0057, respectively) and the Exe group (P = 0.0002 and P = 0.0042, respectively). Additionally, the CSE group exhibited a significant increase in lung MMP12 gene expression compared to the healthy control and Exe groups (P = 0.0008 and P = 0.0013, respectively). Notably, the CSE + Exe group showed a significant decrease in MMP12 gene expression in lung tissue compared to the CSE group (P = 0.0015). Furthermore, the CSE and CSE + Exe groups demonstrated a significant increase in TGFB1 gene expression in lung tissue compared to the healthy control group (P < 0.0001 and P = 0.0022, respectively) and the Exe group (P < 0.0001 for both). Conclusions: Our findings indicate that the group exposed to cigarette smoke experienced a significant decrease in elastin levels, accompanied by an increase in MMP12 and TGF-β1 expression. Although aerobic interval training provided some protection against the detrimental effects of cigarette smoke exposure, it was not sufficient to fully reverse the harmful impacts of the disease.

The Greenland spatial fingerprint of Dansgaard–Oeschger events in observations and models

Pleistocene Ice Ages display abrupt Dansgaard-Oeschger (DO) climate oscillations that provide prime examples of Earth System tipping points-abrupt transition that may result in irreversible change. Greenland ice cores provide key records of DO climate variability, but gas-calibrated estimates of the temperature change magnitudes have been limited to central and northwest Greenland. Here, we present ice-core δ15N-N2 records from south (Dye 3) and coastal east Greenland (Renland) to calibrate the local water isotope thermometer and provide a Greenland-wide spatial characterization of DO event magnitude. We combine these data with existing records of δ18O, deuterium excess, and accumulation rates to create a multiproxy "fingerprint" of the DO impact on Greenland. Isotope-enabled climate models have skill in simulating the observational multiproxy DO event impact, and we use a series of idealized simulations with such models to identify regions of the North Atlantic that are critical in explaining DO variability. Our experiments imply that wintertime sea ice variation in the subpolar gyre, rather than the commonly invoked Nordic Seas, is both a sufficient and a necessary condition to explain the observed DO impacts in Greenland, whatever the distal cause. Moisture-tagging experiments support the idea that Greenland DO isotope signals may be explained almost entirely via changes in the vapor source distribution and that site temperature is not a main control on δ18O during DO transitions, contrary to the traditional interpretation. Our results provide a comprehensive, multiproxy, data-model synthesis of abrupt DO climate variability in Greenland.

Intranasal administration of GRP78 protein (HSPA5) counteracts the neurodegeneration in the locus coeruleus in a model of chronic sleep restriction in rats

Chronic sleep restriction (sleep less than 6 hours per day) due to the workload and a decrease in sleep quality is an endemic disease in modern society. Chronic sleep deprivation causes serious neuropsychiatric disorders associated with irreversible neurodegenerative changes in the brain. The search for pharmacological agents that can reduce the risk of neurodegeneration as a result of chronic sleep loss is an urgent task issue for biomedicine. Intranasal administration of glucose-regulated 78 kDa heat shock protein (GRP78) has a neuroprotective effect in a rat model of Parkinson´s disease. The neuroprotective potential of intranasally administered GRP78 in chronic sleep deprivation has not been previously studied. The aim of the study is to find out whether preventive intranasal administration of GRP78 is able to weaken and/or stop the process of neurodegeneration in the locus coeruleus in the model of chronic sleep restriction (SR) in rats. The study was conducted on 6 months old male Wistar rats. For sleep deprivation, a validated method of a swinging platform was used in the mode: 3 hours of sleep deprivation and 1 hour of rest continuously for 5 days. Recombinant human protein GRP78 was administered intranasally two days before the start of SR and during 5 days of SR. Cellular and molecular changes in the locus coeruleus during SR and during the administration of GRP78 were studied using immunohistochemistry and Western blotting. It was shown that chronic SR leads to the degeneration of 30% of noradrenergic neurons in the locus coeruleus, that was associated with an increase in the levels of activated caspases-3 and 9. This indicates the development of apoptosis along the mitochondrial pathway. No signs of reactive microgliosis were found in the model of chronic SR in rats. We have demonstrated that intranasally administered GRP78 penetrates and accumulates in the neurons of the locus coeruleus, GRP78 counteracts the death of neurons along the path of apoptosis. The data obtained allows to consider GRP78 as a potential neuroprotective agent for the prevention of pathological consequences of chronic sleep deprivation.

VIABILIDADE DA ENERGIA FOTOVOLTAICA EM CARUARU

Renewable energy is an increasingly prominent topic due to the urgent need to reduce greenhouse gas emissions and combat global warming, which can lead to irreversible climate changes. In the state of Pernambuco, there is a growing popularity of solar energy, driven by its significant generation potential and ease of installation. Alongside these factors, there is an increase in the number of companies offering solar projects and installations for small consumers, enabling access to self-generated energy for both residences and businesses. However, despite these advantages, recent changes have raised questions about the viability of solar energy, particularly for the middle and lower classes. Thus, the purpose of this study is to analyze whether solar energy is feasible for residents of Caruaru or if further changes are needed to make it a realistic option.

Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?

Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area. We present an 80-year-old woman with AMD in both eyes, demonstrating progressive changes over a 2-year follow-up. While the right eye developed cRORA with vision decline, the left eye exhibited unexpected restoration of the outer retinal layers within the cRORA lesion. This finding challenges the notion of "end-stage atrophy" in GA development and highlights the potential reversibility of early atrophic lesions. Recognizing these dynamics has implications for the development of targeted therapies aimed at preserving vision in AMD's early stages.

Reversibility in Structural Dynamics on Pt−Ni Bimetallic Nanocrystals under Redox Conditions

AbstractThe reversibility of structural change in a bimetallic catalyst during the chemical reaction is an essential factor to determine the catalytic stability. Herein, we investigate the surface modulation of three Pt−Ni bimetallic alloy nanoparticle compositions (Pt3Ni1, Pt1Ni1, and Pt1Ni3) under alternating redox cycles. We validate trends in the structural change of the three compositions of Pt−Ni nanoparticles via spectroscopic/microscopic investigations at bulk and atomic levels. Pt‐rich Pt−Ni nanoparticles exhibited higher reversibility in structural change during the repeated redox cycles. On the contrary, Ni‐rich Pt−Ni nanoparticles showed irreversible structural changes, leading to the segregation and separation of Ni species from the alloy, which could deactivate the catalysts. This work demonstrates the reversibility of structural dynamics in alloy catalysts depending on their composition, providing fundamental insights for developing ideal bimetallic catalysts.

Equivalent Circuit Model for Electrochemical Impedance Spectroscopy of Commercial 18650 Lithium‐Ion Cell Under Over‐Discharge and Overcharge Conditions

AbstractThis study endeavors to assess the impedance responses exhibited by 18650 Graphite||LiCoO2 (C6||LCO) cells under conditions of over‐discharge and overcharge. The impedance measurements are conducted at a potential of 4.20 V, followed by subjecting the cells to over‐discharge and overcharge scenarios. It is observed that the impedance magnitude experiences augmentation in both instances. Upon reaching a potential of 2.70 V, the electrochemical attributes of the cells revert to their normal state post over‐discharge. However, the impedance characteristics persist even upon exceeding a potential of 4.70 V. These observations imply that overcharge induces enduring alterations in impedance behavior, while over‐discharge is a reversible phenomenon. To delve deeper into the underlying mechanisms, an equivalent circuit process model is constructed. This model elucidates that over‐discharge of Li‐ion batteries is reversible, indicating the potential for restoration of original impedance behavior upon recharge. Conversely, overcharge precipitates permanent alterations in impedance behavior, engendering irreversible changes in battery characteristics. In summation, this study underscores the criticality of meticulously managing the charging and discharging processes of Li‐ion batteries to avert irreversible impairment to impedance behavior, thereby safeguarding battery performance and longevity.

Upconverting thermal history paint for investigations of short thermal events

The main goal of the work was to develop phosphorescent coating for investigations of surface temperature distribution resulted from short duration and high energy thermal events such as small rocket engine testing. For that purpose, we developed thermal history paint with upconverting Gd2O3: Er3+, Yb3+, Mg2+ nanopowder. The developed paint was heated by Joule effect with precise control over temperature and heating time. Photoluminescence signal of cooled samples was excited with 980 nm laser and collected in automatic manner with use of an optical fibre probe connected to photospectrometer. The results show that irreversible changes of paint emission are temperature and heating time specific for calcination temperatures from 700 °C to 1150 °C. Calibration curves were prepared for heating times of 10, 60 and 180 seconds. Finally, 2D surface temperature samples were determined with use of upconverting thermal history paint and compared to IR camera and pyrometric measurements. The results indicate that uncertainty of temperature measurement below 10 °C was achieved for temperatures above 1000 °C. It has been demonstrated that developed thermal history paint allows for measurements of 2D surface temperature distribution with high spatial resolution and good agreement to standard measurements techniques like thermal camera and pyrometer.

Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.

Sjögren's syndrome (SS) or Sjögren's disease (SjD) is a systemic autoimmune disease clinically manifested as sicca symptoms. This disease primarily impacts the functionality of exocrine glands, specifically the lacrimal and salivary glands (SG). SG fibrosis, an irreversible morphological change, is a severe consequence that occurs in the later stages of the disease due to sustained inflammation. However, the mechanism underlying SG fibrosis in SS remains under-investigated. Glandular fibrosis may arise from chronic sialadenitis, in which the interactions between infiltrating lymphocytes and epithelial cells potentially contributes to fibrotic pathogenesis. Thus, both immune and non-immune cells are closely involved in this process, while their interplays are not fully understood. The molecular mechanism of tissue fibrosis is partly associated with an imbalance of immune responses, in which the transforming growth factor-beta (TGF-β)-dependent epithelial-mesenchymal transition (EMT) and extracellular matrix remodeling are recently investigated. In addition, viral infection has been implicated in the pathogenesis of SS. Viral-specific innate immune response could exacerbate the autoimmune progression, resulting in overt inflammation in SG. Notably, post-COVID patients exhibit typical SS symptoms and severe inflammatory sialadenitis, which are positively correlated with SG damage. In this review, we discuss the immune and non-immune risk factors in SG fibrosis and summarize the evidence to understand the mechanisms upon autoimmune progression in SS.

Forensic assessment of maternal deaths from the COVID-19 during the 2021 pandemic

BACKGROUND: According to the literature, the mortality rate from SARS-CoV-2 infection among pregnant women is up to 25%. The high-risk group for the development of severe forms of COVID-19 includes pregnant women with extragenital pathology. Obstetric tactics are determined by the severity of the condition of the mother and fetus, as well as the duration of pregnancy. The decision on early delivery is made as a result of an interdisciplinary medical consultation. Delivery in the midst of the disease is associated with an increase in maternal mortality. According to the literature, including our own research, it has been established that the basis for favorable perinatal outcomes in patients with severe and moderate forms of COVID-19 is: an adequate assessment of the condition of the pregnant woman and fetus (especially at the outpatient stage, where the pregnant woman goes first), early hospitalization, early initiation of intensive care and timely delivery before the onset of irreversible organ changes in pregnant women. AIM: The aim of this study was to analyze the tactics of pregnancy management, delivery and perinatal outcomes, assessing the quality of medical care at the outpatient and hospital stages provided to pregnant women who died in a specialized obstetric hospital from the extremely severe new coronavirus infection COVID-19 (based on the data of commission forensic examinations). MATERIALS AND METHODS: This retrospective study of pregnancy outcomes was performed in 11 patients who died from complications of extremely severe COVID-19 in a regional specialized obstetric hospital in Russia based on the data of commission forensic examinations performed in the Bureau of Forensic Medical Examination (Saint Petersburg, Russia) in 2021, at gestation periods of 28–34 weeks (n = 7) and 37–39 weeks (n = 4) in the context of assessing the quality of medical care in the field of obstetrics and gynecology. We confirmed the diagnosis of the new coronavirus infection COVID-19 in 10 (90.9%) patients by SARS-CoV-2 RNA identification using polymerase chain reaction in a nasopharyngeal smear on an average of 4.9 ± 3.6 days from the onset of the disease. In one patient, the clinical diagnosis was confirmed postmortem by the detection of SARS-Cov-2 RNA during autopsy (in the trachea, lungs, and spleen). All patients in the hospital underwent a comprehensive anamnestic, clinical and laboratory examination in the amount regulated by the administrative regulations of the Ministry of Health of the Russian Federation that were relevant at the time of providing medical care. Nine (81.8%) patients sought medical help from a local therapist on 3.1 ± 1.6 days from the onset of the disease and received outpatient treatment for 3.4 ± 1.8 days, two patients not seeing a doctor and receiving outpatient care. The average time before admission to the specialized obstetric hospital was 6.0 ± 2.2 days from the onset of the disease. RESULTS: During the forensic assessment of the medical records of deceased patients, significant defects in the quality of medical care were identified in the framework of this study at the stages of information collection, diagnosis, treatment, and succession. An indirect causal relationship was established between the most significant defects in the quality of medical care and adverse pregnancy outcomes, since the cause of death or critical conditions were individually determined severe complications, rather than defects in medical care, which, nevertheless, does not exclude their significance in the totality of causes of severe maternal outcomes. CONCLUSIONS: The data obtained indicate the need for earlier delivery in pregnant women with the new coronavirus infection COVID-19 before the appearance of irreversible changes in patients with progressive respiratory failure, multiple organ failure syndrome, systemic inflammatory response syndrome, and cytokine storm.

Holocene benthic foraminifera ecological succession in the Panamanian Caribbean

Benthic foraminifera assemblages from a 452 cm long sediment core (GAL18) were collected from a mangrove forest on the Caribbean coast of Panama. The core spans the last ∼5200 cal yrs. B.P. Ninety-six benthic species were recorded in the sedimentary sequence. The most frequent and abundant were the calcite hyaline species Ammonia batava, Ammonia tepida, Ammonia ariakensis, Elphidium articulatum, Elphidium cristobalense, and Cribroelphidium galeroense. The second most abundant were four porcelaneous species: Quinqueloculina cf. araucana, Quinqueloculina cf. poeyana, Quinqueloculina neocostata and Quinqueloculina seminulum. There were also scattered species of agglutinant taxa along the core and in modern sediments. Micropaleontological, sedimentological, and geochemical analyses allowed the recognition of four lithologic units that were consistent with four paleoenvironmental scenarios of ecological succession. (I) The Estuarine Zone deposited at ∼5200–3600 cal yrs. B.P. suggests the development of a mangrove ecosystem along a channeled tidal area with estuarine water exchange and dominant species from brackish waters such as Ammonia and Cribroelphidium. Isotopic (δ13Corg, δ15N), geochemical (C/N, Ca/Ti, K/Rd, Fe/Ca), and pollen data also show a polyhaline environment with bio-calcite production and active coastal weathering. (II) The Seaward Zone deposited between ∼3600–1250 cal yrs. B.P., closest to marine waters, with an overall increase in benthic species, like the euhaline Quinqueloculina spp., and other calcareous organisms. (III) The Transition Zone was deposited amid 1250–650 cal yrs. B.P. when the area experienced less frequent flooding by tidal waters, dominated by polyhaline Elphidium and Ammonia spp., and the establishment of a mangrove ecosystem influenced by changing salinity, as the sea level almost reached its modern position. Finally, (IV) the Landward Zone deposited over the last 650 cal yrs. B.P., where the lack of benthic foraminifera and bio-calcite deposits contrast with high amounts of organic carbon and vegetal debris, which supports that the core site was located further inland than in previous intervals. This multiproxy study features subtle but irreversible changes that a fringe mangrove community can experience over time, highlighting the complex relationship between the coastal region and the sea.

A retrospective multicenter cohort study of differences in clinical characteristics of Infantile Hemangiomas in preterm and term infants: Prematurity increases risk of permanent cutaneous sequelae

BackgroundWe observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with increased risk of scarring. ObjectiveTo compare the clinical features of localized IH in preterm versus term infants. MethodsA retrospective study at three tertiary referral centers was conducted on 830 consecutive patients with localized IH. ResultsPreterm infants had a significantly higher incidence of superficial IH (75% in <33weeks, 57% in 33-<37 weeks, and 50% in term infants, p=0.007). Overall, their IH had thicker superficial components (p<0.001) and more stepped borders (p<0.001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD=6.2) months, with no difference between gestational age. LimitationsThe retrospective design and use of non-standardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers. ConclusionPreterm infants have features of IH that have obvious implication for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred.

Atrial refractoriness early after transcatheter aortic valve implantation TAVI in patients with severe aortic stenosis and sinus rhythm.

Aortic valve stenosis (AS) is a common valvular heart disease, especially in the elderly, and is associated with a high prevalence of atrial fibrillation. Although the risk of atrial fibrillation is expected to decrease after the intervention, atrial fibrillation develops in many patients undergoing surgical or percutaneous transaortic valve implantation. We aimed to evaluate atrial refractoriness since it may play a key role in the occurrence of atrial fibrillation after transaortic valve implantation. Seventy-nine consecutive patients who underwent TAVI between October 2021 and May 2023 were enrolled in this trial. Sixty-seven patients underwent electrophysiology study before and after TAVI. We evaluated the changes in PA and AH intervals, as well as atrial effective refractory periods. Besides the hemodynamic changes, atrial effective refractory periods increased, and atrial effective refractory period dispersion (39.8±21.6 vs. 31.1±18.0) decreased significantly after TAVI. The change in atrial effective refractory period dispersion after TAVI was correlated only with the changes in left ventricular end-diastolic pressure (r=0.77, P=0.001) and the changes in aortic gradient (r=0.4, P=0.001). The independent variables affecting the changes in atrial effective refractory period dispersion were basal pro-BNP levels, besides the changes in left ventricular end-diastolic pressure and aortic gradient after transaortic valve implantation. Our results show an acute improvement in atrial refractoriness after TAVI, though high atrial fibrillation rates are reported in the literature. The timing of aortic valve replacement is important, as irreversible maladaptive changes might have already developed by the time of intervention.

Peripheral nerve traction injury modeling in an experiment

Background. Peripheral nerve (PN) injuries can lead to significant functional impairment and reduced quality of life. Functional recovery of PN is a complex process dependent on many factors, some of which can be controlled to improve outcomes. The number of wounded people with damage to the peripheral nerves of the limbs can be up to 25 % in war conditions. The degree of disability of patients is 65–70 %, so the issue of restoring peripheral nerves is extremely relevant, especially during wartime. The purpose was to develop a model of PN traction injury in an experiment resulting from longitudinal stretching of the sciatic nerve using a tool modified based on a standard self-retaining retractor, which provides the possibility of reproducing traumatic conditions that most accurately imitate real clinical cases. Materials and methods. The study was conducted on 20 outbreed male rats (average weight of 225 ± 55 g) kept in standard conditions of the vivarium of the State Institution “Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine” in compliance with current norms of bioethics. The animals were divided into two groups: the first one (n = 10) — traction injury of the nerve, withdrawal from the experiment after 15 days with further examination of the damaged area with the light and electron microscopy. The second group of animals (n = 10) — traction injury of the nerve, withdrawal from the experiment after 30 days with further examination of the damaged part of the nerve with the help of light and electron microscopy. Before surgery, on the 15th and 30th day after simulating injury (before the nerve harvesting for morphological analysis), the sciatic functional index (SFI) was determined using the walking track test in groups I and II of animals, respectively. Rats were maintained on a standard 12-h light/dark cycle with free access to food and water. The experiment ended by removing the animals from the experiment by injecting a lethal dose of thiopental sodium. For a more detailed analysis, on the 15th and 30th day after the start of the experiment, repeated surgical interventions were performed to collect the appropriate sections of the nerve for morphological examination. For accurate identification of the proximal end of the nerve, the method of applying a ligature to the epineurium was used, which allowed to clearly demarcate the studied areas for further analysis. Structural changes in the nerve tissue were analyzed using light and electron microscopy, which provided high detail of morphological characteristics. Results. At the beginning of the experiment, before traction injury, the SFI in the first group was 2.26 ± 0.27, and in the second group — 3.14 ± 0.53. Fifteen days after injury simulation, the SFI in the first group was 68.90 ± ± 1.61, and in the second group — 70.31 ± 1.75, the difference between the indicators was statistically insignificant (p ≥ 0.05). When comparing the SFI before and after injury, the difference was statistically significant (p &lt; 0.0014 and p &lt; 0.0032, respectively). Thirty days after injury simulation, the SFI in the second group was 32.27 ± 1.13 and, compared to the indicator on the 15th day after the injury, it differed statistically significantly in favor of the indicator after 30 days (p &lt; 0.0026). From the biomechanical point of view, three main types of injuries can be distinguished, when traction is the main traumatic mechanism: elastic stretching, inelastic (plastic) stretching and rupture. Elastic stretching is characterized by the return of the nerve to its original length after removal of traction. With a further increase in the stretching force, the nerve enters the phase of plastic deformation, during which irreversible changes in its structure occur, such as the rupture of axons, endoneural and perineural sheaths. When a certain threshold of stretching is exceeded (in particular, when the hook was moved along racks at position of 9, 10, 11 teeth), nerve rupture occurred. The results of morphological studies are planned to be described in detail in future scientific publications. Conclusions. 1. The model of the peripheral nerve traction injury is objective as evidenced by the sciatic nerve functional index. This technique is easily reproducible and does not require expensive and complex equipment. 2. The use of a model of peripheral nerve traction injury in an experiment, with the aim of studying the therapeutic effects in this type of trauma, will allow to expand the understanding of its patho- and morphogenesis and to improve treatment strategy. 3. Extrapolation of this model to clinical practice will allow to improve the treatment of victims with the consequences of combat injuries to peripheral nerves, where a similar mechanism of trauma often occurs.

Spectral signatures of soil horizons and soil orders from Wisconsin

AbstractWe used mid‐infrared (MIR) spectra (4000–600 cm−1) to identify and classify soil orders and soil horizons from 102 pedons across five soil orders (Alfisols, Entisols, Mollisols, Spodosols, and Histosols). The soils were analyzed for texture, total carbon, pH, and elemental properties. Random forest models were used to group the spectra of master horizons (O, A, E, B, and C), B horizons (Bs, Bt, and Bw), and the five soil orders. The prediction accuracies for the master horizons and B horizons were 0.81 and 0.89, respectively. The Kappa coefficient was 0.71 for the prediction of master horizons and 0.73 for the prediction of B horizons. The soil orders had an overall accuracy of 0.73 and a Kappa coefficient of 0.64. Histosols exhibited unique absorption characteristics at 2930 and 2860 cm−1 that differed distinctly from mineral soils. The MIR spectra accurately distinguished the O horizons. The spectral curve of topsoil of Spodosols was comparable to the O horizons. Spodosols under forest had A horizons with high organic matter and were classified accurately. Entisols (Psamments) displayed absorption peaks associated with sand, facilitating their differentiation from the other soil orders. The model struggled to discern subtle differences among some soil orders, and identification is hampered if soils undergo irreversible changes upon drying. However, our results showed that MIR spectra can be used for effectively identifying and classifying soil orders as well as soil horizons.

The effect of alcohol on brain structures involved in the formation of addiction

Annotation. The process of forming alcohol addiction leads to the occurrence of irreversible changes in the human body, which can be fatal. Neurons of the brain are among the most sensitive structures to the effects of ethanol. Brain neurons are one of the most sensitive structures to the action of ethanol. Understanding the mechanism of formation of alcohol dependence can help in the treatment of patients with this disorder. Therefore, goal is a detailed study of the areas of the brain that are responsible for the formation of this disorder. For this, was analyzed the PubMed database. Articles were selected that discussed the areas of the brain involved in the formation of this disorder, changes in dopaminergic and GABAergic neurons, increased or decreased expression of proteins that regulate neuroplasticity of these areas during chronic ethanol consumption. For the convenience of searching, articles are grouped by publication years: 2000-2010, 2011-2018, and 2019-2023. According to the results of this study, we believe that the hippocampus, prefrontal cortex (PFC), nucleus accumbens, the amygdala and the ventral tegmental area (VTA) are key brain structures involved in the formation of addiction; these areas are part of the mesocorticolimbic reward pathway; the hippocampus is responsible for the formation of pleasant memories, it can decrease under the influence of ethanol, which leads to the loss of episodic memory; the PFC has an influence on decision-making that is based on experience, alcohol suppresses PFC activity; the adjacent nucleus stimulates a person through dopamine connections to relapse, because plasticity changes under the influence of ethanol; the amygdala - is the center of formation of positive and negative emotions, and alcohol withdrawal reduces the activity of this structure and causes stress, while chronic use of ethanol, on the contrary, activates the amygdala; The VTA has connections with all structures of the mesocorticolimbic pathway, it can both facilitate alcohol use and stimulate aversion to it. Conclusion: in our opinion, these structures are the most important in the process of forming addiction. The perspective of the research, in our opinion, is the study of the molecular mechanisms of addiction.

Features of treatment tactics for some clinical and pathogenetic variants of gastroesophageal reflux disease

Relevance Gastroesophageal reflux disease is a disease that has a complex mechanism of formation, causing a variety of clinical and pathogenetic features, realised during the development of the pathological process. The variety of tactical and methodological solutions in its treatment is formed from this premise. Material and Methods The authors have 25 years of experience, which consists in direct participation in the diagnostic and therapeutic process in several thousand patients with gastroesophageal reflux, including several hundred patients with cylindrocellular metaplasia and Barrett’s oesophagus. Results Determination of indications for surgical treatment of complicated and uncomplicated gastroesophageal reflux disease is a complex and responsible decision. It is necessary to take into account: the nature and severity of cylindrocellular metaplasia, the size of axial hernia and its combination with insufficiency of cardiac jejunum, the severity of jejunal insufficiency and preservation of diaphragmatic constriction, the state of Gis angle, the type and severity of reflux - esophagitis, as well as the presence of irreversible changes in the mucosa to determine the indications for correction and surgical tactics. It is necessary to pay attention to the severity of clinical manifestations of the disease.