Volume Reduction Research Articles

Adverse childhood experiences and left hippocampal volumetric reductions: A structural magnetic resonance imaging study

BackgroundAdverse childhood experiences (ACEs) have been associated with volume alterations of stress-related brain structures among aging and clinical populations, however, existing studies have predominantly assessed only one type of ACE, with small sample sizes, and it is less clear if these associations exist among a general population of young adults. ObjectiveThe aims were to describe structural hippocampal volumetric differences by ACEs exposure and investigate the association between ACEs exposure and left and right hippocampal volume in a student sample of young adults. Methods959 young adult students (18–24 years old) completed an online questionnaire on ACEs, mental health conditions, and sociodemographic characteristics. Magnetic resonance imaging (MRI) was used to measure left and right hippocampal volume (mm3). We used linear regression to explore the differences of hippocampal volumes in university students with and without ACEs. ResultsTwo thirds of students (65.9%) reported ACEs exposure. As ACEs exposure increased there were significant volumetric reductions in left (p < 0.0001) and right hippocampal volume (p = 0.001) and left (p = 0.0023) and right (p = 0.0013) amygdala volume. After adjusting for intracranial brain volume, sex, age, and depression diagnosis there was a negative association between ACEs exposure and left (β = −22.6, CI = −44.5, −0.7, p = 0.0412) but not right hippocampal volume (β = −18.3, CI = −39.2, 2.6, p = 0.0792). After adjusting for intracranial volume there were no associations between ACEs exposure and left (β = −9.2, CI = −26.2, 7.9 p = 0.2926) or right (β = −5.6, CI = −19.9,8.8 p = 0.4466) amygdala volume. ConclusionsHippocampal volume varied by ACEs exposure in young adult students. ACEs appear to contribute to neuroanatomic differences in young adults from the general population.

Effects of single and combined urinary polycyclic aromatic hydrocarbon effects on lung function in the U.S. adult population

BackgroundThe impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults.MethodsData from 4040 adults in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites.ResultsAnalyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers.ConclusionThis study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment.

Early activation of macrophage-2 with IL-4 in stromal vascular fraction increases VEGF levels and adipocyte count and maintains volume of fat graft in Wistar rats (Rattus norvegicus)

Several previous studies have demonstrated the benefits of early macrophage 2 activation fat grafts supplemented with macrophage culture. However, this approach is considered impractical in clinical settings because of intraperitoneal induction use. The aim of this study was to investigate the effect of early stromal vascular fraction (SVF) macrophage-2 activation with IL-4 on fat graft survival compared to SVF alone using an animal model for better fat graft viability. This experimental study included inguinal fat harvesting, isolated with collagenases to retrieve the SVF, and then injected with a combination of fat graft and SVF (0.3 mL) into the scalp region. The intervention group received an IL-4 intralesional injection on the third day, and the fat grafts were biopsied on days 7, 14, and 30. The primary outcomes were the final volume of the fat graft, vascular endothelial growth factor (VEGF) expression, and the adipocyte cell count using perilipin staining on immunohistochemistry examination. The group receiving IL-4 exhibited significantly higher VEGF on days 7, 14, and 30 (p=0.009, 0.009, and 0.021, respectively). Similarly, the IL-4 treatment significantly increased the perilipin concentration on days 7, 14, and 30 (p=0.008, 0.008, and 0.029, respectively). In this group, VEGF concentration was significantly increased on day 14 as compared to day 7 (p=0.009), while no significant difference was observed in the control group (p=0.090). Additionally, the IL-4 group displayed significantly less reduction of fat graft volume than the control group, as observed on days 7, 14, and 30 (p=0.009, 0.009, and 0.021, respectively). Overall, the study underscores the potential benefits of early M2 polarization in fat grafting, as well as providing practical advantages for improving fat graft volume retention.

Experimental investigation and numerical analysis of material removal efficiency using abrasive microaggregates in grinding processes of Ti6Al4V

Reducing plastic interactions between abrasive grains and the material being processed improves grinding efficiency and lowers energy consumption. Widening the cutting zone with abrasive grains enhances chip formation and reduces lateral material displacement. This can be achieved by using abrasive microaggregates.The paper presents an experimental analysis of grinding with modified wheels containing abrasive microaggregates. It examines how these microaggregates impact the grinding wheel's surface microgeometry and material removal efficiency. The study measured changes in the number, surface area, volume, and spacing of active contact areas on the grinding wheel active surface. A comparative analysis using the Shos indicator showed that abrasive microaggregates promote the formation of active areas with wide cutting edges perpendicular to the cutting direction.Finite element method simulations confirmed that abrasive microaggregates enhance material removal by widening the micro-cutting zone and increasing lateral resistance, which reduces the formation of flashes along the cutting path. The study also assessed how these surface features impact the roughness of the ground surface. A comparative analysis of roughness parameters showed a statistically significant reduction in surface, volume, hybrid, and functional parameters when using grinding wheels with abrasive microaggregates. This analysis was conducted using bootstrap statistical hypothesis tests.

Remote Sensing-Based Drought Monitoring in Iran’s Sistan and Balouchestan Province

Drought is a natural phenomenon that has adverse effects on agriculture, the economy, and human well-being. The primary objective of this research was to comprehensively understand the drought conditions in Sistan and Balouchestan Province from 2002 to 2017 from two perspectives: vegetation cover and hydrology. To achieve this goal, the study utilized MODIS satellite data in the first part to monitor vegetation cover as an indicator of agricultural drought. In the second part, GRACE satellite data were employed to analyze changes in groundwater resources as an indicator of hydrological drought. To assess vegetation drought, four indices were used: Vegetation Health Index (VHI), Vegetation Drought Index (VDI), Visible Infrared Drought Index (VSDI), and Temperature Vegetation Drought Index (TVDI). To validate vegetation drought indices, they were compared with Global Land Data Assimilation System (GLDAS) precipitation data. The vegetation indices showed a strong, statistically significant correlation with GLDAS precipitation data in most regions of the province. Among all indices, the VHI showed the highest correlation with precipitation (moderate (0.3–0.7) in 51.7% and strong (≥0.7) in 45.82% of lands). The output of vegetation indices revealed that the study province has experienced widespread drought in recent years. The results showed that the southern and central regions of the province have faced more severe drought classes. In the second part of this research, hydrological drought monitoring was conducted in fifty third-order sub-basins located within the study province using the Total Water Storage (TWS) deficit, Drought Severity, and Total Storage Deficit Index (TSDI Index). Annual average calculations of the TWS deficit over the period from April 2012 to 2016 indicated a substantial depletion of groundwater reserves in the province, amounting to a cumulative loss of 12.2 km3 Analysis results indicate that drought severity continuously increased in all study basins until the end of the study period. Studies have shown that all the studied basins are facing severe and prolonged water scarcity. Among the 50 studied basins, the Rahmatabad basin, located in the semi-arid northern regions of the province, has experienced the most severe drought. This basin has experienced five drought events, particularly one lasting 89 consecutive months and causing a reduction of more than 665.99 km3. of water in month 1, placing it in a critical condition. On the other hand, the Niskoofan Chabahar basin, located in the tropical southern part of the province near the Sea of Oman, has experienced the lowest reduction in water volume with 10 drought events and a decrease of approximately 111.214 km3. in month 1. However, even this basin has not been spared from prolonged droughts. Analysis of drought index graphs across different severity classes confirmed that all watersheds experienced drought conditions, particularly in the later years of this period. Data analysis revealed a severe water crisis in the province. Urgent and coordinated actions are needed to address this challenge. Transitioning to drought-resistant crops, enhancing irrigation efficiency, and securing water rights are essential steps towards a sustainable future.

The Usefulness of Portable Echo in the Preoperative Mapping of Lymphaticovenular Anastomosis.

This study evaluated the effectiveness of a pocket-sized ultrasound device in preoperative planning for lymphaticovenular anastomosis (LVA) to enhance lymphedema treatment outcomes. A retrospective analysis was performed on 24 patients who underwent LVA for secondary upper extremity lymphedema between June 2020 and August 2022. Patients were categorized into two groups: the ultrasound group, which used a pocket-sized device (Vscan Air), for preoperative vein identification, and a control group that did not. Preoperative lymphatic mapping was performed using indocyanine green lymphography, and suitable veins for anastomosis were identified using ultrasound. Upper extremity lymphedema index and incision length were compared. Participants in the ultrasound group had a shorter average incision length (2.85 ± 0.48 cm) than those in the control group (3.23 ± 0.78 cm, p = 0.038), indicating a more targeted and minimally invasive approach. Although volume reduction rates were not significantly different, the pocket ultrasound device facilitated more precise vein selection, enhancing surgical planning. Pocket-sized ultrasound devices provide a cost-effective and practical solution for vein identification during LVA, particularly in resource-limited settings. While high-frequency ultrasound offers superior resolution, portable devices could become standard tools for lymphatic surgery with continued technological advancement.

Clinical Improvements after Endoscopic Lung Volume Reduction with Valves in Patients with advanced Emphysema and a 6-Minute-Walk-Test ≤140 m at Baseline

BackgroundData regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with very low 6-Minute Walk Test (6-MWT) is limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6-MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutics benefits and increased complication risk.Study Designs and MethodsThis study utilized data from the Lungenemphysemregister e.V., a large German national multi-center prospective open label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6-MWT ≤140 m and dyspnea primarily attributed to hyperinflation.ResultsFifty-four patients with a baseline 6-MWT ≤140 m and 365 patients with a baseline 6-MWT between 140 m and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6-MWT ≤140 m at baseline had a lower FEV1, DLCO and higher symptom burden. In the 3-month-follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6-MWT ≤140 m at baseline showed significantly more 6-MWT improvement compared to patients with baseline 6-MWT between 140 m–450 m. Moreover, complication rates were similar in both groups.InterpretationIn summary, the data indicates that ELVR may be an effective and safe treatment for emphysema patients with a very low 6-MWT ≤140 m, if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6-MWT.

Efficacy of echolaser smart interface-guided laser ablation in volume reduction of symptomatic benign thyroid nodules.

The management of benign symptomatic thyroid nodules until recent years has been limited to surgery, radioactive iodine treatment, or surveillance which is associated with the burden of morbidity of complications or symptom non-relief as well as cost. Laser ablation has emerged as a minimally invasive alternative, this uses laser energy to thermally ablate nodule tissue, leading to volume reduction and symptom relief. Long-term treatment response data is growing but remains limited in the United States. Our study aims to quantify the effectiveness of laser ablation in reducing the volume of thyroid nodules over a 12 to 18-month period. Retrospective review of data was conducted for 63 adults with cytologically benign, solid symptomatic thyroid nodules ranging from 1.333 cm3 to 103.794 cm3 in volume. Ultrasound-guided laser thermal ablation was performed on all nodules using EchoLaser X4 Smart Interface device with 1064 nm diode laser to deliver total ablation energy (joules), calculated per device guidelines. Serial sonographic volume measurements were conducted 1 month, 3 -6 months, 6 - 12 months, and 12 to 18 months post-ablation intervals. Study cohort was comprised of 63 thyroid nodules. reduction in nodule volume increased progressively over time, with median reductions of 46.05% [STD 21.8] at 1 month, 60.33% [STD 20.1] at 3-6 months, 68.69% [STD 18.8] at 6-12 months, and 64.04% [STD 19.27] at 12-18 months. A total of 62, 56, 42, and 17 nodules had available data for analysis at these respective intervals. This study demonstrated a marked progressive reduction of thyroid nodule volume following ablation. The treatment appears to be consistently effective in reducing symptoms across a wide range of nodule sizes, although the degree of volume reduction varies. The results of our study underscore the potential of laser ablation as a viable treatment option for thyroid nodules, with a sustained reduction in nodule volume observed over an extended post-procedure period.

IMPROVEMENT OF THE TEST METHODOLOGY OF AIRCRAFT VIDEO RECORDING EQUIPMENT UNDER THE CONDITIONS OF A SPECIAL PERIOD

The introduction of weapons and military equipment at the stage of Russia's armed aggression requires the rational use of human resources, standard means of measurement, registration and indication as part of measurement systems and further processing of the results obtained in automated systems for collecting and processing information for its use during tests of serial (modernized) samples of OVT. The rapid development of technical means of measurement, transformation and exchange of data within and between systems require the improvement of test methods for video recording of aircraft, which take into account the peculiarities of the development of electronic equipment of aviation equipment and are based on a unified approach to the problem of optimal use of resources. Modern means of video registration have quite justifiably been widely used in the Armed Forces of Ukraine. The research was conducted using the methods of the theory of system analysis, synthesis, comparison, and generalization. The purpose of the article is to develop a typical methodology for testing aircraft video recording equipment in the conditions of a special period. To achieve the goal, the following was done: to analyze the existing methods of testing domestic and foreign aircraft video registration means; to consider an improved model of functioning and the technology of conducting tests of means of video registration of aircraft with a reduction in volume; to develop a typical methodology for conducting tests of aircraft video registration devices in the conditions of a special period. The results of the analysis should be taken into account when justifying ways to reduce the amount of tests in the conditions of a special

Effects of Polyvinyl Chloride Microplastics on the Reproductive System, Intestinal Structure, and Microflora in Male and Female Mice

The pervasive use of plastics in numerous industrial sectors has resulted in the circulation of microplastics across diverse ecosystems and food chains, giving rise to mounting concerns regarding their potential adverse impacts on biological systems and the environment. The objective of this experiment was to investigate the distinct effects of microplastic-polyvinyl chloride (PVC) exposure on the reproductive system, intestinal tissue structure, and intestinal microbial flora of both male and female mice. A total of 24 4-week-old Kunming mice were randomly assigned to one of four groups: male control group (CM), female control group (CF), male PVC test group (PVCM), and female PVC test group (PVCF) (n = 6). The findings revealed that in terms of the reproductive system, the PVCM group exhibited an impaired testicular structure with an irregular arrangement and a significant reduction in spermatogonia, spermatocytes, and spermatozoa within the seminiferous tubules (p &lt; 0.01). The PVCF group exhibited a notable decrease in ovarian follicles (p &lt; 0.01), accompanied by a reduction in uterus volume, fallopian tube volume, and muscle layer thickness, all of which also decreased significantly (p &lt; 0.01). In comparison to the control groups, exposure to PVC resulted in a reduction in the width and height of the intestinal villi, accompanied by an increase in crypt depth. This led to a significant alteration in the ratio of villus height to crypt depth (V/C) (p &lt; 0.01). Moreover, a reduction in microbial species diversity was observed within both the PVCM and PVCF groups; additionally, it was accompanied by contrasting changes in relative abundance and functional gene profiles among the major intestinal flora constituents. In summary, the findings indicate that PVC induces damage to both male and female mice reproductive and digestive systems, further exhibiting notable sex-dependent effects on mouse intestinal microflora composition, which correlates significantly with its impact on reproductive organs.

Multiomics-Based Outcome Prediction in Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR).

Objectives: This retrospective study aims to develop a multiomics approach that integrates radiomics, dosiomics, and delta features to predict treatment responses in brain metastasis (BM) patients undergoing PULSAR. Methods: A retrospective study encompassing 39 BM patients with 69 lesions treated with PULSAR was undertaken. Radiomics, dosiomics, and delta features were extracted from both pre-treatment and intra-treatment MRI scans alongside dose distributions. Six individual models, alongside an ensemble feature selection (EFS) model, were evaluated. The classification task focused on distinguishing between two lesion groups based on whether they exhibited a volume reduction of more than 20% at follow-up. Performance metrics, including sensitivity, specificity, accuracy, precision, F1 score, and the area under the receiver operating characteristic (ROC) curve (AUC), were assessed. Results: The EFS model integrated the features from pre-treatment radiomics, pre-treatment dosiomics, intra-treatment radiomics, and delta radiomics. It outperformed six individual models, achieving an AUC of 0.979, accuracy of 0.917, and F1 score of 0.821. Among the top nine features of the EFS model, six features came from post-wavelet transformation and three from original images. Conclusions: The study demonstrated the feasibility of employing a data-driven multiomics approach to predict treatment outcomes in BM patients receiving PULSAR treatment. Integrating multiomics with intra-treatment decision support in PULSAR shows promise for optimizing patient management and reducing the risks of under- or over-treatment.

Advancing greener LNG-fueled vessels: Compact simultaneous reduction system for CH4, NOX and CO2 emissions

Stringent ship regulations necessitate simultaneous emission reductions, challenged by cargo loss and energy constraints. This study proposes a compact reduction system that simultaneously mitigate CH4, NOX, and CO2 emissions onboard LNG-fueled vessels. The proposed system integrates two pivotal technologies: a metal support-based compact methane oxidation catalyst (MOC)-selective catalytic reduction (SCR) system to capture CH4 and NOX, and a cryogenic CO2 capture (CCC) system to capture and store CO2 in its solid phase utilizing LNG's cold energy. This innovative approach addresses two challenges. First, the compact MOC-SCR system employs metal support with an enhanced surface area-to-volume ratio surpassing the capabilities of ceramic support materials, achieving a volume reduction of 80.02% and 79.82% respectively. Secondly, the CCC system significantly lowers specific energy consumption by 61.54% by harnessing LNG's cold energy compared to the absorption-based CO2 capture system. As a result, the proposed system not only reduces CH4, NOX, and CO2 emissions simultaneously with a high capture rate but also reduces volume and weight. Furthermore, it achieves a high CO2 capture rate of 92.12%, while diminishing cargo losses by 25.30%. These findings provide valuable guidance for developing environmentally sustainable vessels, aligning with the continuously increasing stringency of regulations.

Abnormal changes in neuropsychological function, brain structure and cerebral perfusion in patients with unruptured intracranial aneurysms.

Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. In the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results. Compared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function. UIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

Early Adversity Affects Cerebellar Structure and Function-A Systematic Review of Human and Animal Studies.

Recent research has highlighted cerebellar involvement in cognition and several psychiatric conditions such as mood and anxiety disorders and schizophrenia. Attention-deficit/hyperactivity disorder and autism spectrum disorder have been linked to reduced cerebellar volume as well. Cerebellar alterations are frequently present after early adversity in humans and animals, but a systematic integration of results is lacking. To this end, a systematic literature search was conducted in PubMed, Web of Science, and EBSCO databases using the keywords "early adversity OR early life stress" AND "cerebellum OR cerebellar." A total of 45 publications met the inclusion criteria: 25 studies investigated human subjects and 20 reported results from animal models. Findings in healthy subjects show bilateral volume reduction and decreased functional connectivity within the cerebellum and between the cerebellum and frontal regions after adversity throughout life, especially when adversity was assessed with the Childhood Trauma Questionnaire. In clinical populations, adults demonstrate increased cerebellar volume and functional connectivity after adversity, whereas pediatric patients show reduced cerebellar volume. Animal findings reveal cerebellar alterations without necessarily co-occurring pathological behavior, highlighting alterations in stress hormone receptor levels, cell density, and neuroinflammation markers. Cerebellar alterations after early adversity are robust findings across human and animal studies and occur independent of clinical symptoms.

Enhanced Real‐Time Monitoring of Catalytic Therapy Efficacy with Dual‐Channel MRI and Fluorescent Platform

AbstractCatalytic therapies, such as chemodynamic therapy and ferroptosis, harness the tumor microenvironment to enhance the specificity and penetration of treatments, thus improving targeted tumor therapy. Despite these advancements, treatment effectiveness varies due to individual differences, making precise monitoring of drug activity and dosage essential to optimize therapy. Traditional imaging strategies, which monitor metal ion release or reactive oxygen species production, frequently fail to well correlate with therapeutic outcome. Herein, this study have developed an integrated self‐monitoring catalytic therapy platform that combines palladium‐ and manganese‐based nanoparticles (PdMn NPs) with caspase‐3 activated probe (Casp probe). Dual‐channel MRI and fluorescent probe, responsive to both low pH and caspase‐3 activity, significantly enhances the accuracy of real‐time therapeutic evaluations, allowing for early reporting treatment response (in 6 h), earlier than tumor volume reduction (8 days). This approach improves the assessment of therapeutic outcomes and aligns with the shift toward individualized cancer treatment protocols.

Regional changes in the free Achilles tendon volume in response to repeated submaximal contractions

IntroductionThe Achilles tendon (AT) may become smaller in volume following acute bouts of heavy and sustained loading likely because of transient fluid exudation to the periphery and this could augment cellular mechanotransduction and tendon adaptation. Given the structure of the AT is distinct across its length, regional changes in the free AT volume may occur in response to loading. This study aimed to investigate whether the change in tendon volume in response to repeated submaximal loading is distinct across the free AT length. MethodsSixteen ATs of healthy males and females (age 24.4 ± 9.4 years, body mass 70.9 ± 16.1 kg, height 1.7 ± 0.1 m) were scanned at rest using freehand 3D ultrasound. Scanning was done before and immediately after submaximal (75 %) voluntary isometric plantarflexion contractions (8 s) involving four sets of ten repetitions. Regional volumetric changes were assessed across the free AT length by dividing the tendon into distal, mid, and proximal regions. ResultsSignificant reduction in the free AT volume occurred across all tendon regions in response to the intervention, however, the mid- region exhibited the greatest reduction in volume compared to the proximal region (P = 0.025). DiscussionThe fact that volume reduction was greatest in the mid-region compared to the proximal region of the free AT may suggest greater tendon adaptation, via mechanotransduction pathways, in the mid-region and this may be important for tendon health and injury prevention.

Blood-Brain Barrier-Penetrating Metal-Organic Framework Antioxidant Nanozymes for Targeted Ischemic Stroke Therapy.

Overproduction of reactive oxygen species (ROS) during reperfusion in ischemic stroke (IS) severely impedes neuronal survival and results in high rates of morbidity and disability. The effective blood-brain barrier (BBB) penetration and brain delivery of antioxidative agents remain the biggest challenge in treating ischemic reperfusion-induced cerebrovascular and neural injury. In this study, a metal-organic framework (MOF) nanozyme (MIL-101-NH2(Fe/Cu)) with ROS scavenging activities to encapsulate neuroprotective agent rapamycin is fabricated and decorating the exterior with BBB-targeting protein ligands (transferrin), thereby realizing enhanced drug retention and controlled release within ischemic lesions for the synergistic treatment of IS. Through the receptor-mediated transcellular pathway, the transferrin-coated MOF nanoparticles achieved efficient transport across the BBB and targeted accumulation at the cerebral ischemic injury site of mice with middle cerebral artery occlusion/reperfusion (MCAO/R), wherein the nanocarrier exhibited catalytic activities of ROS decomposition into O2 and H2O2-responsive rapamycin release. By its BBB-targeting, antioxidative, anti-inflammatory, and antiapoptotic properties, the MOF nanosystem addressed multiple pathological factors of IS and realized remarkable neuroprotective effects, leading to the substantial reduction of cerebral infarction volume and accelerated recovery of nerve functions in the MCAO/R mouse model. This MOF-based nanomedicine provides valuable design principles for effective IS therapy with multi-mechanism synergies.

Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review.

Cerebrovascular events (CVEs) are a dreaded complication of transcatheter aortic valve replacement (TAVR). They are associated with significant mortality, morbidity, and reduced quality of life and impose a significant burden to health care systems. Although the rates of clinical stroke have reduced since the advent of TAVR, it remains an important complication, particularly as TAVR is increasingly utilized. CVE may occur at the time of the TAVR, as a direct consequence of the procedure, or may occur later, related to thrombosis of the prosthetic valve, atrial fibrillation, and other comorbidities. Imaging of the brain has revealed a high prevalence of subclinical cerebral infarcts (68%-98%) associated with the TAVR procedure. Although their clinical significance has not been fully established, clinically evident CVE ranges between 3% and 5% in patients considered at high operative risk to between 1% and 3% in low operative risk patients. Periprocedural CVEs are largely the result of embolization of the thrombus and tissue derived from the valve, vasculature, or myocardium. Cerebral embolic protection devices have been studied in multiple trials, with some evidence supporting a reduction in new cerebral lesion volume, number, and potentially disabling strokes. However, thus far, there is no robust evidence that they reduce the overall stroke rate. The number and severity of comorbidities, in particular, new-onset atrial fibrillation, are associated with CVEs. Valve thrombosis diagnosed using computed tomography as areas of hypoattenuated leaflet thickening has been identified in 10% to 15% of patients. This is a dynamic process associated with an increase in CVEs, but that resolves with anticoagulation or sometimes without it. Routine use of anticoagulation compared with a single antiplatelet agent is associated with an increased risk of bleeding, without any additional alleviation in risk of thromboembolism. Future studies to improve risk stratification could facilitate the tailoring of preventive therapies to patients at high risk of CVE, who stand to gain the most benefit.

Cell stress and phase separation stabilize the monomeric state of pseudoisocyanine chloride employed as a self-assembly crowding sensor

Cellular stress and ageing involve an increase in crowding and aggregation of amylogenic proteins. We here investigate if crowding is the intrinsic cause of aggregation and utilise a previously established non-protein aggregation sensor, namely pseudoisocyanine chloride (PIC). PIC shows fibrillization in cells into a highly fluorescent J-aggregated state and is sensitive to crowding. Surprisingly, cell stress conditions stabilise the monomeric rather than the aggregated state of PIC both in the cytoplasm and in stress granules. Regarding the different physiochemical changes of the cytoplasm occurring upon cell stress, involving volume reduction, phase separation and solidification, the intrinsic crowding effect is not the key factor to drive associated self-assembly processes.

7770 Damage of Ovarian Vasculature by Chemotherapies induces Ovarian Dysfunction in Mice

Abstract Disclosure: W. So: None. R. Dong: None. Y. Luan: None. A. Abazarikia: None. S. Kim: None. Background: Chemotherapy demonstrates efficacy to destroying cancer cells; however, it can inadvertently impact normal healthy cells, leading to irreversible side effects, particularly affecting the ovaries in female patients. Female cancer survivors encounter endocrine dysfunction and infertility due to ovarian damage caused by gonadotoxic cancer therapies. The ovary, a vital organ responsible for producing oocytes and endocrine hormones, faces significant challenges following such treatment. A study with premenopausal breast cancer patients reported a significant reduction in ovarian blood flow and volume immediately following chemotherapy. The preservation of ovarian function depends on the ovarian vasculature in supporting the development and maintenance of ovarian follicles. Despite its importance, the relationship between ovarian vasculature and follicle following chemotherapy has not been studied. Results: To investigate the direct impacts of chemotherapy, ovaries from postnatal 5 CD-1 mice were subjected to testing with three chemotherapeutic agents: cisplatin (CDDP), cyclophosphamide (CPA), and doxorubicin (DOXO). The expression of CD31/PECAM-1 (platelet endothelial adhesion molecule) exhibited a significant decrase after 96 hours of culture with 4-HC, an active metabolite of CPA. This reduction implies that ovarian vasculature was also compromised when chemotherapy eliminated immature follicles. In order to evaluate the influence of vascular endothelial growth factor (VEGF) in safeguarding both vasculature and ovarian follicles, ovaries were co-cultured with VEGF165 or VEGF165b in combination with chemotherapy. Interestingly, pre-treatment with VEGF165 before 4-HC led to an increased expression of CD31 in the cortex area, while VEGF165b further diminished CD31 expression compared to treatment with 4-HC alone. Additionally, adolescent CD-1 mice were intraperitoneally injected with CDDP, CPA, or DOXO, and ovaries were harvested one week after injection. Ovaries treated with chemotherapeutic agents exhibited a reduction in ovary weight and decreased CD31 expression compared to control mice. Conclusions: We propose that these chemotherapeutic agents not only induced the loss of ovarian follicles but also affected ovarian vasculature in mice. This suggests a potential decrease in folliculogenesis within the ovary, coupled with the depletion of ovarian reserve, as the delivery of nutrients and oxygen to growing ovarian follicles may be compromised. VEGF165 may play a beneficial role in maintaining ovarian function by safeguarding ovarian vasculature following chemotherapy. Understanding these intricate dynamics is essential for developing strategies to mitigate the negative impact of cancer therapies on reproductive health in female cancer survivors, particularly in preserving endocrine function and reproductive lifespan. Presentation: 6/2/2024