Evident Signs Research Articles

In vitro ultrastructure and biodegradation of activated plasma albumin gel derived from human samples: A prospective observational study.

In soft tissue regeneration, the clinical efficacy of fibrin membranes has been a pressing concern. The key to this efficacy lies in the stability of membrane and its controlled absorption. Human serum albumin, with its influence on the formation and stability of fibrin networks, could hold the key to developing a more stable alternative. This study investigates the ultrastructure and biodegradability of plasma albumin-activated gel, a potential game-changer in the field. Blood samples were collected from the participants and centrifuged to obtain the concentrated growth factor. The poor platelet plasma syringe was placed inside the activated plasma albumin gel device. The ultrastructure of the membrane was examined using a scanning electron microscope (SEM). The weight difference was measured over 21 days to investigate the biodegradability of the samples. Twenty-two samples were prepared from six individuals (three males and three females). Based on SEM images, activated albumin gel after 21 days in Hank's solution exhibited a significant decrease in density and evident signs of surface degradation. The weight was significantly reduced after 21 days (p <0.05). In the present study, the investigation of the ultrastructure and biodegradability of activated albumin gel showed that, based on the observed weight difference, the amount of biodegradation is high, and it may be necessary to use a thicker membrane compared to the conventional thickness of the connective tissue graft. Enhanced stability and biocompatibility: The study highlights plasma albumin-activated gel's potential as a soft tissue scaffold, demonstrating significant biodegradation and structural changes that support cell infiltration and nutrient exchange, essential for tissue regeneration. Controlled degradation profile: Plasma albumin gel offers a prolonged biodegradation period compared to conventional fibrin membranes, making it suitable for applications requiring stable, long-lasting scaffolds in soft tissue regeneration. Future clinical applications: Findings suggest that thicker plasma albumin membranes may be needed for optimal effectiveness, paving the way for further exploration in clinical trials and animal models to validate this approach in soft tissue grafting. This study investigates plasma albumin-activated gel as a promising material for supporting soft tissue repair, particularly in periodontal regeneration. Traditional materials, such as fibrin membranes, are often used to aid healing, but their rapid breakdown can limit effectiveness in the body. Plasma albumin, a protein naturally found in human blood, might offer a more stable alternative by forming a longer-lasting structure. In this study, researchers processed blood samples from participants to create the gel, examining its structure under a powerful microscope and tracking changes in weight over 21 days to assess its breakdown. Results showed that the gel gradually became less dense and more porous, allowing for cell movement and nutrient flow-both critical for tissue repair. Additionally, a significant reduction in weight indicated a controlled breakdown over time. These findings suggest that plasma albumin-activated gel may serve as a more durable scaffold for soft tissue regeneration, potentially improving healing outcomes in periodontal applications where a stable, longer-lasting material is needed.

Notch1 blockade by a novel, selective anti-Notch1 neutralizing antibody improves immunotherapy efficacy in melanoma by promoting an inflamed TME

BackgroundImmune checkpoint inhibitors (ICI) have dramatically improved the life expectancy of patients with metastatic melanoma. However, about half of the patient population still present resistance to these treatments. We have previously shown Notch1 contributes to a non-inflamed TME in melanoma that reduces the response to ICI. Here, we addressed the therapeutic effects of a novel anti-Notch1 neutralizing antibody we produced, alone and in combination with immune checkpoint inhibition in melanoma models.MethodsAnti-Notch1 was designed to interfere with ligand binding. Mice were immunized with a peptide encompassing EGF-like repeats 11–15 of human Notch1, the minimal required region that allows ligand binding and Notch1 activation. Positive clones were expanded and tested for neutralizing capabilities. Anti-Notch1-NIC was used to determine whether anti-Notch1 was able to reduce Notch1 cleavage; while anti-SNAP23 and BCAT2 were used as downstream Notch1 and Notch2 targets, respectively. K457 human melanoma cells and the YUMM2.1 and 1.7 syngeneic mouse melanoma cells were used. Cell death after anti-Notch1 treatment was determined by trypan blue staining and compared to the effects of the gamma-secretase inhibitor DBZ. 10 mg/kg anti-Notch1 was used for in vivo tumor growth of YUMM2.1 and 1.7 cells. Tumors were measured and processed for flow cytometry using antibodies against major immune cell populations.ResultsAnti-Notch1 selectively inhibited Notch1 but not Notch2; caused significant melanoma cell death in vitro but did not affect normal melanocytes. In vivo, it delayed tumor growth without evident signs of gastro-intestinal toxicities; and importantly promoted an inflamed TME by increasing the cytotoxic CD8+ T cells while reducing the tolerogenic Tregs and MDSCs, resulting in enhanced efficacy of anti-PD-1.ConclusionsAnti-Notch1 safely exerts anti-melanoma effects and improves immune checkpoint inhibitor efficacy. Thus, anti-Notch1 could represent a novel addition to the immunotherapy repertoire for melanoma.

Investigating the influence of possible liver fibrosis on mortality in patients with coronary artery disease - a post-hoc ISCHEMIA trial analysis

Abstract Background There is a plethora of studies demonstrating that comorbidities (e.g., diabetes and renal dysfunction) directly influence outcomes in patients undergoing PCI or CABG for coronary artery disease (CAD). Yet, liver dysfunction is not really included in current risk assessment beyond the presence of liver cirrhosis. Retrospective single center evidence now suggests that the presence of liver fibrosis may be an indicator of elevated risk. Using the FIB-4 score, where increasing values correlate with increaseing degrees of histological liver fibrosis, liver fibrosis could already be detected with all required laboratory values (AST, ALT, platelets) within normal range. In addition, the study suggests a beneficial effect of off-pump CABG when FIB-4 is elevated. This finding contradicts current randomized evidence, negating any difference between off and on-pump CABG. Since randomized trials always suffer from strong selection of low risk patients, it is conceivable that trial patients may primarily have low FIB-4 scores. Purpose To address the distribution of FIB-4 scores in a selected trial population with CAD (from the ISCHEMIA trial) and relate the degree of liver fibrosis reflected by the score to mortality. Methods The FIB-4 score was calculated for all patients. According to the standard classification, a value of greater than 1.2 reflects a 90% chance of the presence of histological liver fibrosis. The imapct of FIB-4 on late all-cause mortality was assessed as a continuous and categorical variable using maximally selected rank statistics determined FIB-4 cutoff. Cox regression model was peformed including the adjustment for the main CAD risk factors. Results Among 3735 included patients, 58.8% had a FIB-4 value above 1.2. Patients with higher FIB-4 score (cutoff= 1.64) were slighly older, presented higher prevalence of male sex, prior PCI and CABG, and prior history of atrial fibrillation and cerebrovascular disease. FIB-4 score was directly associated with higher risk of mortality when addressed as a continouos variable and as a categorical variable (Fig. 1). This relationship was evident in the overall population and in all subsets (PCI, CABG and no revascularization; Fig. 2). Conclusions The use of Fib-4 to determine the degree of liver fibrosis may be powerful to predict mortality in CAD populations which may not show any evident clinical signs of liver dysfunction. The Fib-4 distribution in this trial population, considered as selected and low risk, warrants investigating randomized trial populations having compared on- and off-pump CABG.Figure 1.Mortality: overall population.Figure 2.Mortality: by therapy subsets.

The state of psychological and immunological indicators in graduate students of a medical university

Training future doctors for professional practice usually entails building awareness and embracing the significant responsibility inherent in the field. This, in turn, leads to significant psycho-emotional stress by the time of graduation from academic institution. With the aim of identifying the correlation between homeostatic system indicators, a comparative analysis was conducted to characterize the immunological and psychological parameters of final-year medical university students, contingent upon their respective training programs. The study involved sixth-year students of the Therapeutic and Preventive Faculty [TPF] (29 individuals) and the Military Training Center [MTC] (34 individuals) of Rostov State Medical University, a Federal State Budgetary Educational Institution of Higher Education. The exclusion criteria for all participants included the presence of chronic diseases and any infectious process of any origin within three months prior to the study. The groups were similar in terms of age (23.8±1.82 and 23.9±2.2 years, respectively), gender (all male), and corresponded to health group I. Psychological evaluation was conducted employing the Spielberger–Hanin Scale to gauge levels of personal and situational anxiety. The assessment of immunological status was carried out at the Scientific Research Institute of Clinical Immunology using standard methodological approaches. Registration cards for immunopathology analysis were used to characterize health status over the year. Analysis of the obtained data from psychological questionnaires revealed that students of the Therapeutic and Preventive Faculty, compared to their counterparts from the Military Training Center, demonstrated a higher degree of situational and, particularly, personal anxiety. Differences in the immune response system between the compared groups were identified with regards to indicators that characterize both adaptive and innate immunity. These differences were expressed in a more significant number of circulating regulatory T lymphocytes, a less pronounced lytic potential of effector cells, a greater number of TLR9+ monocytes with a decrease in the proportion of cells of the monocyte series carrying HLA-DR in medical students compared to their counterparts studying in the medical service officers’ program. Thus, the period of psychological preparation in a medical university for the commencement of professional activity varies based on the characteristics of the educational process and proves to be more effective for sixth-year students of MTC. Students from the TPF exhibit more pronounced psycho-emotional stress compared to their counterparts in military medical training, leading to evident signs of immune system dysregulation. It is imperative to develop strategies for timely detection of changes in both psychological and immunological adaptive capacities.

Intratympanic injection of MSC-derived small extracellular vesicles protects spiral ganglion neurons from degeneration

Sensorineural hearing loss is one of the most prevalent sensory deficits. Spiral ganglion neurons (SGNs) exhibit very limited regeneration capacity and their degeneration leads to profound hearing loss. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been demonstrated to repair tissue damage in various degenerative diseases. However, the effects of MSC-sEV on SGN degeneration remain unclear. In this study, we investigated the efficacy of MSC-sEV for protection against ouabain-induced SGN degeneration. MSC-sEV were derived from rat bone marrow and their components related to neuron growth were determined by proteomic analysis. In primary culture SGNs, MSC-sEV significantly promoted neurite growth and growth cone development. The RNA-Seq analysis of SGNs showed that enriched pathways include neuron development and axon regeneration, consistent with proteomics. In ouabain induced SGN degeneration rat model, MSC-sEV administration via intratympanic injection significantly enhanced SGN survival and mitigated hearing loss. Furthermore, after ouabain treatment, SGNs displayed evident signs of apoptosis, including nuclei condensation and fragmentation, with numerous cells exhibiting TUNEL-positive. However, administration of MSC-sEV effectively decreased the number of TUNEL-positive cells and reduced caspase-3 activation. In conclusion, our findings demonstrate the potential of MSC-sEV in preventing SGN degeneration and promoting neural growth, suggesting intratympanic injection of MSC-sEV is a specific and efficient strategy for neural hearing loss.

Clinical Outcome of Surgical Treatment of Giant Femoral Artery Pseudoaneurysms

Femoral artery was used as an access site for cardiovascular procedures and by IV drug abusers, Femoral Artery Pseudoaneurysm (FAP) was a common complication associated with these procedures. Objective: To evaluate clinical outcome of surgical repair of femoral artery pseudoaneurysms. Methods: The prospective study was conducted in Doctors Hospital, Lahore from October 2022 to October 2023. The study included patients with giant femoral artery pseudoaneurysms who required surgical intervention. Data from a total of 50 patients were included in whom both peripheral vascular interventions and percutaneous cardiac catheterization was performed. Patients were followed up at 1-, 3-, 6- and 12 months postoperatively. SPSS version 23.0 was used for data analysis. Results: All patients underwent open surgical treatment. Of 50 patients, 25 (50%) had SFA pseudoaneurysm, 20 (40%) had CFA pseudoaneurysm and 5 (10%) had PFA pseudoaneurysm. The mean duration of clinical manifestations was 16.30 ± 7.74 days. Surgical repair was successful in all 50 (100%) patients and distal ischemia was fully resolved. There was no case of limb loss or post-operative mortality. One patient had an infection in the groin wound and had raised Total leucocyte count (TLC), which was resolved by early drainage and antibiotic treatment. Patients were followed up at 1, 3, 6, and 12 months and there were no signs of clinical or angiographic evidence of post-operative complications and changes in distal pulse. Conclusion: Surgical repair was first-line treatment for giant FAP. It was clinically feasible and has a high success rate and low complication rate.

Clinical experience of a patient with hemopericardium

Introduction: pericardial effusion is a frequent entity in daily practice, which can occur due to a wide range of pathologies, it is the result of an increase in the blood content of the pericardial sac.Case presentation: female patient, white skin, 93 years old, presented with a fall on her own feet, was taken to the Orthopedics and Traumatology Department where a diagnosis of intertrochanteric right hip fracture was made and admission to the observation room was indicated for subsequent surgical treatment. The patient began to become tachycardic 110/min, hypotensive 80/50 mmHg, she began to resuscitate with volume responding to fluid minirection (4ml/Kg). Hematocrit was repeated and found to be 0.25, her state of shock was attributed as hypovolemic hemorrhagic. Signs of tissue hypoperfusion persisted, despite the prescribed measures and increased vasopressor requirements. It was decided to perform an echocardiogram where there were evident signs of pericardial effusion. Pericardial window and hemostasis of the bleeding site were performed, achieving the survival of this case. Conclusions: hemopericardium is an entity with a reserved prognosis, which may occur due to a wide range of traumatic and non-traumatic pathologies; imaging methods are a key diagnostic tool, transthoracic echocardiography is the first line method for its evaluation. Therapeutic percutaneous approach, surgical exploration, as well as pericardiocentesis are therapeutic methods

Focal spleen lesions in loiasis: A pilot study in Gabon.

Infection with the filarial nematode Loa loa, endemic in Central and Western Africa, has been associated with increased morbidity and mortality. A number of reports described the presence of spleen nodules, originating from degenerating microfilariae, in humans and animals infected with L. loa. The long-term consequences of this process on individuals chronically exposed to infection in terms of spleen function and possible link with excess mortality are unknown. The aim of this study was to evaluate the prevalence of focal spleen lesions, their evolution over time, and markers of spleen function, in individuals with L. loa infection living in highly endemic areas of Gabon. This was a cross-sectional study followed by a longitudinal study of the subset of individuals with spleen nodules. Two hundred sixteen participants from Ngounié and Moyen-Ogooué provinces of Gabon, reporting a history of eyeworm migration and/or Calabar swelling, were included. Participants were categorized into infected microfilaraemic with low (N = 74) and high (N = 10) microfilaraemia, and symptomatic amicrofilaraemic (N = 132), based on blood microscopy. Howell-Jolly bodies in erythrocytes, as indirect marker of spleen functional impairment, were within normal ranges. On ultrasound, no evident signs of spleen fibrosis or hypotrophy were observed. Multiple spleen hypoechoic centimetric macronodules were observed in 3/216 participants (1.4%), all with microfilaraemic L. loa infection (3.4% of microfilaraemics); macrondules disappeared at the 6-months follow-up examination in 2/3 individuals. Spleen hypoechoic micronodules, persisting at the 6-months follow-up, were detected in 3/216 participants (1.4%), who were all amicrofilaraemic. Transitory spleen macronodules are present in a small but consistent proportion of individuals with microfilaraemic loiasis, appearing a rather benign phenomenon in terms of impact on spleen morphology and function. Their occurrence should be taken into consideration to avoid misdiagnosis and mistreatment. Prevalence and significance of spleen micronodular ultrasound patterns in the general population would be also worth evaluating.

Evolutionary pathways of disk galaxies with different sizes

This work delves into the complex interaction between disk galaxies and their host dark matter halos. It specifically focuses on scenarios with minimal external ("nurture") influences such as mergers and substantial tidal interactions. The study uncovers the varied evolutionary paths of disk galaxies of different sizes, shaped by the initial conditions of their parent dark matter halos and subsequent internal processes. Thus, we can explore the ``nature'' of these galaxies. From the TNG50 simulation, a sample of 836 central disk galaxies with tiny stellar halos is chosen to study the inherent evolution of galaxies driven by nature. These galaxies are classified as compact, normal, or extended by referencing their locations on the mass-size ($M_ $) diagram. Scaling relations were then established to measure the correlations driven by internal mechanisms. This research demonstrates the distinctive evolutionary pathways of galaxies with different sizes in IllustrisTNG simulations, primarily driven by their nature. It is confirmed that disk galaxies inherit the angular momentum of their parent dark matter halos. More compact galaxies form earlier within halos that exhibit a lower specific angular momentum through heightened star formation during the early phase at redshifts above 2. During the later phase, the size of extended galaxies experiences more pronounced growth by accreting gas with a high angular momentum. Additionally, we reveal that many key characteristics of galaxies are linked to their mass and size: (1) compact galaxies tend to exhibit higher metal content, proportional to the potential well, $ M_ star R_ $; (2) compact galaxies host more massive bulges and black holes, along with a higher central concentration. Furthermore, our analysis indicates that galaxies of all types continue to actively engage in star formation, with no evident signs of quenching attributed to their varying sizes and angular momenta.

Analysis of three primary prostatic sarcoma cases and literature review.

The objective of this study is to evaluate the clinical presentations, diagnostic approaches, and treatment modalities for primary prostate sarcoma postradical prostatectomy, aiming to enhance its diagnosis and management. We retrospectively reviewed the clinical records of three male patients diagnosed with primary prostate sarcoma at Beijing Chaoyang Hospital, affiliated with Capital Medical University, from February 2014 to February 2024. All patients underwent transrectal prostate biopsies, which informed the decision to proceed with laparoscopic radical prostatectomies. After surgery, one patient received a combination of epirubicin and ifosfamide as immunotherapy, along with external beam radiotherapy. After comprehensive discussions regarding potential benefits and risks, the remaining two patients decided against undergoing radiotherapy and chemotherapy. Based on the pathological examination results, two patients were diagnosed with stromal sarcoma and one with spindle cell sarcoma, all classified as high-grade sarcomas. Immunohistochemical analysis showed that all three cases were positive for VIMENTIN, but other results did not show significant specificity. During the follow-up period, one patient died within 12 months, and two patients were lost to follow-up after 6 months. However, there were no evident signs of recurrence observed during the follow-up period. Primary prostate sarcoma is extremely rare and typically has a poor prognosis once diagnosed. Early diagnosis should be based on pathological and immunohistochemical testing results, followed by prompt surgical treatment and adjuvant radiotherapy and chemotherapy. Despite these measures, recurrence is common, underscoring the need for a detailed and appropriate treatment plan and systematic therapy for affected patients.

Erosion and intergranular corrosion induced failure of S31254 stainless steel – Case study on Venturi scrubber in a natural gas purification plant

The flue gases such as SO2, SO3, and CO2 generated during the purification process of sulfur-containing natural gas need to be treated to a certain concentration before they can be discharged into the atmosphere. The flue gas unit of a purification plant in Sichuan adopts the new Cansolv flue gas treatment process. After running for a period of time, the Venturi scrubber experienced severe corrosion failure, resulting in equipment shutdown and significant economic losses. This paper utilizes an actual failed device as a case study to analyze the corrosion environment of the Venturi scrubber. It conducts a comprehensive failure analysis, encompassing material mechanical properties, metallographic analysis, and failure microstructure analysis, aiming to elucidate the reasons behind the Venturi scrubber failure. Systematic analysis shows that the manufacturing materials used in this scrubber meet all design requirements. However, flue gas at temperatures reaching 280 °C enters the scrubber tower at a flow rate exceeding 10 m/s. The dissolution of acidic gases leads to a significant drop in the pH of the cooling water to 1, manifesting evident signs of erosion corrosion and intergranular corrosion on the material surface. These observations suggest that erosion and intergranular corrosion in high-temperature acidic environments are the predominant factors contributing to the corrosion failure of the Venturi scrubber.

Prediction of Parkinson’s Disease using Handwriting Analysis and Voice Dataset- A Review

Parkinson's disease is a common neurological movement illness that impairs motor coordination. Parkinson’s disease (PD) symptoms and severity, however, differ from person to person. By extracting insights, trends, and possibilities from the data, data research can be utilized to uncover solutions to problems in medical research by utilizing data, machine learning algorithms, and cutting-edge technology. Among the less evident early signs of Parkinson's disease are tremors, muscle stiffness, imbalance problems, and difficulty walking. There is currently no test to detect the illness early on, when symptoms might not be evident. However, handwriting and hand- drawn subjects in humans have been linked to PD. In addition to being a useful tool for PD prediction, speech smearing functions as an early warning system. In order to control symptoms and maybe halt the disease's progression, early detection makes it possible to organize treatments and intervene promptly. For those with Parkinson's disease, early application of certain therapies and medications can extend survival and enhance quality of life.

Chronic thromboembolic pulmonary hypertension in acute pulmonary embolism: a risk factor evaluation study

Aims: Pulmonary thromboembolism (PTE) is a highly mortal disease, defined by presence of thrombus partially or completely obstructing pulmonary arteries and/or veins, commonly originated from deep venous system. Chronic thrombroembolic pulmonary hypertension (CTEPH) is a rare complication of PTE with high mortality if not treated properly. In recent studies, incidence of CTEPH was found between %0,4-9,1. Due to clinically silent PTE in roughly %50 of patients, it is difficult to pinpoint the exact incidence of CTEPH. In this study, we aim to investigate PTE patients during their long-term follow up to observe CTEPH presence and evaluate CTEPH risk factors. Methods: Patients who had been evaluated in emergency service and/or admitted to pulmonary medicine ward between January 2014 and January 2017 with PTE diagnosis confirmed by computed tomography pulmonary angiogram (CTPA) were accepted retrospectively into the study. Their echocardiography, CTPA and lower extremity venous Doppler ultrasonography at 3., 6. and 12. months follow up were also included. In the patient group with pulmonary arterial pressure (PAP ) above 50 mmHg and residual thrombosis at CTPA, ventilation-perfusion scintigraphy had been performed and was added to the study. Among those suitable for CTEPH, right cardiac catheterization had been done to confirm the diagnosis and accepted as CTEPH. In addition to this group, patients who were not found suitable for right cardiac catheterization but wereclinically suitable for CTEPH are also included in the CTEPH group. Results: Average age of patients included into the study was 62(±16, 5), with 71 (%39) being male and 111 (%61) female. As for risk factors, 130 (%71,4) had acquired, 16 (%8,8) had genetic and the rest 36 (%19,8) did not have any prominent risk factors. At time of diagnosis, 10 patients were accepted as massive, 26 as sub massive and the rest 139 were considered non-massive PTE. Due to hemodynamic instability, 7 (%3,8) patients were given thrombolytic therapy. During 1 year follow-up, 5 (%2,7) patients were diagnosed with CTPH. When further investigation was performed on these 5 patients, atrial fibrillation (AF), persistent thrombosis at 12. month follow up CTPA and PAP above 55 mmHg upon time of diagnosis were found significant risk factors (p being 0,001/0,023/0,009 respectively). In multivariate analysis, no independent predictive factors were found in regards to CTEPH diagnosis. Conclusion: CTEPH is a preventable complication of PTE with severe mortality and morbidity if not properly treated. It might prove useful to utilize echocardiography and CTPA together, especially in those in high risk groups, for diagnosis of patients in early stage of CTEPH with no evident signs or symptoms.

Identification of a Novel TP63 Variant in a Chinese Patient with Orofacial Clefts and Ectrodactyly: Case Report and Literature Review.

The TP63 gene is essential for epithelial proliferation, differentiation, and maintenance during embryogenesis. Despite considerable clinical variability, TP63-related symptoms are characterized by ectodermal dysplasia, distal limb malformations, and orofacial clefts. We identified a novel TP63 variant (c.619A > G, p.K207E) in a seven-month-old Chinese patient with orofacial clefts and ectrodactyly but no evident signs of ectodermal dysplasia. This phenotype was rarely reported before. We summarized the presence of the three main TP63-related manifestations in the literature and noted different distributions of CP- and CL/P-related variants regarding p63 structural domains.

Enhancing Hand Fracture Care: A Prospective Study of Artificial Intelligence Application With ChatGPT

BackgroundThe integration of artificial intelligence and machine learning technologies into the medical field has brought about remarkable advancements, particularly in the domain of clinical decision support systems. However, it is uncertain how they will perform as clinical decision makers. MethodsThis prospective cohort study evaluates the potential of incorporating ChatGPT-4 plus into the management of subcapital fifth metacarpal fractures. The treatment recommendations provided by ChatGPT-4 plus were compared with those of two control groups; the attending clinic plastic surgeon and independent expert panel. The primary outcome measures, operative or conservative, were compared between groups. Intra-class correlation of 0.61 infers moderate reliability in the consistency of recommended management plans across all groups. ResultsKey predictors for opting for operative management, regardless of the decision-maker, included clinical signs of scissoring, extension deficit, and radiographic evidence of intra-articular extension. ConclusionThese findings support the potential for AI applications in enhancing diagnostic and treatment decisions

Preliminary Investigation of the Remnants of Low-Latitude Glacial Activity on the Southeastern Margin of the Qinghai–Tibet Plateau

The formation of Quaternary glaciers represented a pivotal event in the climatic and geological history of the Tibetan Plateau. However, due to the scarcity of direct evidence for low-latitude glaciation, the timing and extent of late Quaternary glaciation on the Tibetan Plateau remain controversial. This study focuses on the Liangwang Mountains, which are located in the southeastern part of the Tibetan Plateau and has a maximum elevation of 2820 m, as the subject of investigation. Through a comprehensive application of glacial landform analysis, scanning electron microscopy (SEM)-based micromorphology analysis of quartz sand, and spore-pollen data analysis, we uncovered evident signs of glacial activity in this region during the Quaternary period. Our research identified typical glacial landforms such as cirques, U-shaped valleys, fluted moraines, and terminal moraines. Additionally, spore-pollen analysis revealed a high frequency of fir pollen, indicating cold climatic conditions during that time. Furthermore, the micromorphology analysis of quartz sand further corroborated the glacial origin of these deposits. Based on these combined findings, our study confirms that the Liangwang Mountains experienced glaciation during the Quaternary period, making them glacial relics at the lowest latitude currently known in mainland China. This discovery provides a valuable reference for understanding the paleoclimate and glacial history of the Tibetan Plateau and its surrounding regions.

Difficulties in the treatment of acute sepsis

SUMMARY. The problem of acute sepsis as a polyetiological acyclic disease with peculiar clinical symptoms and diagnostic difficulties, which requires special treatment, is considered. Acute sepsis is the main and most common clinical form of this disease. The predictors of acute sepsis and the variety of clinical manifestations of its two classical stages – septicemia and septicopyemia – are characterized in detail. A typical case of acute sepsis, which was diagnosed only later, is given. In this regard, etiotropic therapy was delayed. Therefore, despite powerful etiotropic therapy, the disease was not limited to acute sepsis, but continued in the form of infectious (septic) endocarditis. The septic nature of infectious endocarditis is due to the presence and persistence of a septic focus in the endocardium, as well as the course of the disease in the form of continuous growth of local inflammatory and destructive changes in primary septic foci and general infectious-metastatic, thromboembolic and immune complex manifestations, which in the absence of special treatment lead to an inevitable fatal outcome, that is, the development of a disease such as sepsis acyclicity. The diagnosis of infective endocarditis is based on the detection of initially reasonably suspicious clinical and then evident paraclinical signs of the disease. Classical clinical and morphological signs of infectious endocarditis, as well as general principles of therapy of such patients, are given.

Hippocampal neuroimmune response in mice undergoing serial daily torpor induced by calorie restriction.

Hibernating animals demonstrate a remarkable ability to withstand extreme physiological brain changes without triggering adverse neuroinflammatory responses. While hibernators may offer valuable insights into the neuroprotective mechanisms inherent to hibernation, studies using such species are constrained by the limited availability of molecular tools. Laboratory mice may serve as an alternative, entering states of hypometabolism and hypothermia similar to the torpor observed in hibernation when faced with energy shortage. Notably, prolonged calorie restriction (CR) induces serial daily torpor patterns in mice, comparable to species that utilize daily hibernation. Here, we examined the neuroinflammatory response in the hippocampus of male C57BL/6 mice undergoing serial daily torpor induced by a 30% CR for 4 weeks. During daily torpor episodes, CR mice exhibited transient increases in TNF-α mRNA expression, which normalized upon arousal. Concurrently, the CA1 region of the hippocampus showed persistent morphological changes in microglia, characterized by reduced cell branching, decreased cell complexity and altered shape. Importantly, these morphological changes were not accompanied by evident signs of astrogliosis or oxidative stress, typically associated with detrimental neuroinflammation. Collectively, the adaptive nature of the brain's inflammatory response to CR-induced torpor in mice parallels observations in hibernators, highlighting its value for studying the mechanisms of brain resilience during torpor. Such insights could pave the way for novel therapeutic interventions in stroke and neurodegenerative disorders in humans.

Optical coherence tomography angiography value for detection of early retinal microvascular changes in systemic hypertension

Purpose The aim of this study was to assess the macula and optic disc vessel density (VD) and perfusion and the anatomical alterations at the fovea and optic nerve in chronic treated hypertension (HTN) patients who exhibited no signs of hypertensive retinopathy using optical coherence tomography angiography (OCTA). Patients and methods This is a prospective case–control study that included 37 participants. They were subdivided into two groups: the hypertensive group that included 22 patients (mean age=51.9±5.9 years), with no clinically evident signs of hypertensive retinopathy, and the control group that included 15 individuals (mean age=48.8±3.7 years) with no known history of HTN or other chronic systemic diseases. OCTA scans covering a 6.0×6.0 mm area for the macula and a 4.5×4.5 mm region for the optic nerve head were performed to evaluate the VD, the foveal avascular zone area, macular thickness, and retinal nerve fiber layer (RNFL) thickness. The correlation of the VD measurements with the RNFL thickness was evaluated. Results The hypertensive patients exhibited a significantly lower overall mean macular VD (45.8±6.0) compared to the control group (48.5±2.9, P=0.017). In addition, they exhibited a significantly lower superficial VD in the superior hemifield (46.4±5.3 and 48.6±2.9, respectively, P=0.030). On the other hand, the deep vascular density in the superior hemifield showed no significant difference between the two groups. In addition, the hypertensive patients were found to have a significantly lower average RNFL thickness (103.2±17.8 μm) compared to the control group (117.1±14.1 μm, P=0.001), with specific statistically significant reductions in the superior (P=0.002) and inferior (P=0.004) sectors. Although the central ganglion cell-inner plexiform layer thickness did not reach statistically significant difference between the two groups (HTN: 50.7±12.0 μm vs. control: 55.7±8.8 μm, P=0.055), the hypertensive group exhibited statistically significant reductions in the ganglion cell-inner plexiform layer thickness in the superior (P&lt;0.001), inferior (P=0.002), nasal (P=0.003), and temporal (P=0.001) sectors compared to the controls. There was no statistically significant difference in the size of the foveal avascular zone between the two groups. Conclusion OCTA revealed subclinical alterations in the retinal microvasculature parameters among the hypertensive patients without clinical signs of hypertensive retinopathy, in comparison to normotensive individuals.

NITRIC OXIDE METABOLISM IN RAT SMALL INTESTINE TISSUES FOLLOWING SURGICAL TRAUMA REPRODUCED IN EXPERIMENTAL MODEL OF POSTTRAUMATIC STRESS DISORDER

The article investigates the parameters of the nitric oxide (NO) system in the small intestine tissues of rats subjected to surgical trauma within an experimental model of post-traumatic stress disorder (PTSD). The study involved 42 white Wistar rats weighing 210-230 g, divided into 6 groups: Group 1 comprised intact animals, Group 2 included animals with the PTSD induced through single-prolonged stress (SPS), Group 3 consisted of rats subjected to a sham surgical operation, Group 4 comprised animals undergoing laparotomy, Group 5 involved rats undergoing a sham surgical operation following SPS, and Group 6 included animals undergoing laparotomy under modeled SPS. Nitric oxide synthase (NOS) activity in small intestine homogenates was assessed using spectrophotometric methods; peroxynitrite formation was determined by analyzing the content of peroxynitrite of alkali and alkaline earth metals. The study has demonstrated the SPS results in evident signs of nitrosative stress in the small intestine tissues of rats: it enhances NOS activity by activating the inducible isoform, reduces the constitutive NOS activity and coupling, and elevates the concentration of peroxynitrites of alkali and alkaline-earth metals. On the 7th day following laparotomy under PTSD modelling, nitrosative stress indicators in the small intestine tissues such as total and inducible NOS activity, as well as peroxynitrite concentrations of alkaline and alkaline-earth metals, significantly surpassed their levels following a single laparotomy under simulated single prolonged stress.