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Quantitative molecular imaging of cardiac fibrosis and response to treatment using a novel collagen III-specific MR imaging probe

Abstract Background Heart failure (HF) remains a major cause of morbidity and death affecting 64 million people globally[1]. Myocardial fibrosis, characterised by changes in type I (COL1) and III (COL3) collagen levels, may lead to HF [2,3]. Cardiac magnetic resonance (CMR) is a preferred method to detect fibrosis non-invasively, however it provides only indirect measures of fibrosis. Molecular imaging can directly visualise fibrosis, but current imaging probes target COL1. Purpose Here, we developed a COL3-specific probe and used molecular CMR imaging to directly quantify, previously undetectable, COL3 remodelling following myocardial infarction and to monitor treatment response. Methods Myocardial infarction (MI) was induced in mice by permanent ligation of the left anterior descending artery (LAD). Functional and molecular CMR images were acquired at days 10 and 21 post-MI in untreated and mice treated with Enalapril (20mg/kg/day) (n=6/group) using a 3T clinical MRI scanner. A subgroup of untreated mice was also imaged using a negative control probe and Gadovist (n=3). Cardiac function was assessed using 2D short-axis cine images of the left ventricle, and late gadolinium enhancement (LGE) images were obtained using T1-weighted 3D inversion recovery (IR) imaging. T1 mapping was performed using a 2D Look-Locker sequence with thirty inversion recovery images. Results Molecular CMR enabled selective profiling of the natural turnover of COL3 after MI with strong signal enhancement at day 10, and decreased enhancement at day 21 when COL3 is replaced by COL1 (Fig. 1A). Quantitative T1 maps discriminated between infarcted and remote myocardium with lower T1 values in the infarct and higher in the remote myocardium. Importantly, there was no enhancement using the scrambled probe or the clinical agent Gadovist. The imaging data were validated by histology (Fig.1B). Mice treated with Enalapril showed similar enhancement at day 10 compared to untreated mice (Fig. 2A). However, at day 21 mice treated with Enalapril showed higher signal enhancement compared to untreated mice, suggesting that Enalapril may prolong the presence of COL3 in the infarcted myocardium. Quantification of signal enhancement showed the increase in LGE volume and R1 relaxation rates within the infarcted myocardium at day 10, the subsequent decrease at day 21 and the prolongation of the COL3 signal at day 21 in enalapril treated mice (Fig.2B-C) Despite changes in cardiac fibrosis detected with molecular imaging, cardiac function was similar between the groups (Fig. 2D), suggesting that molecular change may precede functional changes. Conclusion(s) Quantitative molecular CMR imaging of COL3 enabled visualisation of changes in COL3 after MI and in response to treatment for the first time. This approach may provide insights into the role of COL3 in cardiac fibrosis and provide an non-invasive method to detect fibrosis early, stage fibrosis and monitor therapeutic response.

Identification of new instances of white matter hyperintensities in patients following TAVI (from the CAPITA study)

Abstract A third of patients diagnosed with symptomatic severe aortic valve stenosis and scheduled for transcatheter aortic valve implantation (TAVI) exhibit some level of cognitive impairment. The prospective CAPITA study aimed to systematically evaluate the impact of TAVI on cerebral and cognitive outcomes in patients undergoing the procedure. In this report, we focus on the identification of new incidence of white matter hyperintensities (WMH) and the correlation with changes in cognitive functioning. The CAPITA (CArdiac OutPut, Cerebral Blood Flow and Cognition In Patients With Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation) study is a prospective study of cerebral and cognitive outcomes following TAVI. Patients underwent magnetic resonance imaging (MRI) and extensive neuropsychological testing at baseline and three month follow-up. New cerebral infarcts were defined according to NeuroARC criteria. We examined the incidence of new WMH in terms of volume (Δ mL) and number on FLAIR MRI, and explored the correlation between new WMH and cognitive functioning. A total of 148 patients were included who underwent TAVI between August 2020 and October 2022. Mean age was 80.5±5.7 years, of whom 43% female with a median STS-PROM of 2.0% (IQR 1.4%-2.9%). Median baseline WMH comprised 127 (IQR 32-216) lesions, with a total volume of 13.1 (IQR 7.0-24.6) mL. At 3 months follow-up, the number of lesions increased to 164 (IQR 121-301) lesions, with a total volume of 13.3 (IQR 5.8-21.5) mL. Median WMH volume increase was 0.1 (IQR 0.0-0.3) ml (p=0.02). A total of 9 patients (9.5%) had an increase of 1 mL of WMH or more. At follow-up, 12% of patients exhibited cognitive decline of >0.5SD. These patient tended to have a greater increase in white matter hyperintensity volume (1.26±2.96 ml), compared to the 53% of patients with stable cognition (0.29±0.45 ml) and the 36% of patients with improved cognition (0.31±0.91 ml), (p=0.06). WMH lesions did not exhibit distribution patterns across various locations within the groups characterized by declined, stable, or improved cognition (Figure 1). WMH volumes were higher in patients who experienced postprocedural delirium than in patients without delirium (27.1±14.0 vs 15.0±12.5 mL, p<0.001). In this study, patients with severe symptomatic aortic valve stenosis undergoing TAVI, there was an overall increase of white matter hyperintensity volume between baseline and 3-month follow-up. Up to 12% of patients had cognitive decline, which was associated with new white matter hyperintensities on MRI.

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI >95 g/m2 for women and >115 g/m2 for men with RWT >0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p<0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p<0.001) and after 24 hours (1322 ng/l vs 784, p<0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Diagnostic value of low dose dobutamine stress echocardiography in paradoxical low flow low gradient aortic stenosis

Abstract Background In aortic stenosis with low-gradient scenarios distinguishing between fixed and pseudo-severe stenosis becomes challenging. Low-dose dobutamine stress echocardiography (DSE) is recommended for classical low-flow low- gradient stenosis with reduced ejection fraction. Doubts of DSE's utility in paradoxical low-flow low-gradient (PLFLG) stenosis when ejection fraction is preserved are partially reasoned by proposed inefficiency in generating a contractile reserve 1. Guidelines advocate an integrated approach, combining various clinical and imaging aspects 2. Purpose This study aimed to investigate usefulness of DSE in PLFLG stenosis, identifying specific features to predict the possibility of generating significant stroke volume augmentation and distinguishing fixed aortic stenosis. Methods We identified patients with aortic stenosis who underwent DSE and multi-modality imaging at our centre between 2020 and 2023. Among them, those with PLFLG situations were used for detailed analysis. Multiple linear regression analysis was performed to identify parameters predictive of significant contractile reserve, defined as 20% stroke volume increase from baseline. For patients demonstrating contractile reserve we assessed predefined parameters by receiver operating characteristics (ROC) analysis to predict fixed stenosis defined as final aortic valve area < 1cm² and valve area change <0.2cm² or final mean pressure gradient >40mmHg. For predictive value of Agatston score we conducted post-hoc analysis. Results Among 256 DSE cases, 67 were conducted for PLFLG stenosis. Patients were 82 years of median age and mostly female (63%). Symptoms included dyspnea in 90% and angina in 40% of cases. Baseline echo showed median aortic valve area (indexed to body surface area) of 0.8cm² (0.44cm²/m²) with mean pressure gradient of 20mmHg. Contractile reserve was inducible in 70% of patients, of which 74% showed criteria of fixed stenosis. Higher left ventricular end-diastolic diameter (LVESD) and lower baseline systolic flow-rate were predictive for contractile reserve (p<0.05). Among patients with contractile reserve ROC for baseline mean pressure gradient, acceleration time (median 0.08s; range 0.04-0.11s) and acceleration time to ejection time index (0.28; range: 0.148-0.458) revealed good prediction of fixed stenosis in DSE meanwhile Agatston calcium score (median 1076; range: 301-8821) did not (figure 1). No correlation was found between Agatston score probability of severe stenosis and aortic valve pressure gradient behavior with increased stroke volume (figure 2). Conclusion DSE proves to be a useful a method in the differentiation between fixed and pseudo-severe stenosis in PLFLG situation. Our findings question the predictive value of Agatston score for aortic valve behavior with increase of stroke volume and warrant further investigations regarding value of acceleration time and acceleration time to ejection time index in those patients.Receiver operating characteristicsPost-hoc analysis of Agatston score

Detection of biventricular volume increase in overweight and obese by using a novel index of the ideal human - a single center non-contrast-enhanced cardiac CT study

Abstract The bi-ventricular volume (BVV) can be measured from non-contrast-enhanced CT images in patients referred for coronary artery calcium (CAC) scoring. Such determined BVV has been found to correlate with left ventricular mass and to predict increased risk of all-cause and CV mortality in patients with type 2 diabetes mellitus. Currently, no data are available that quantifying the effect of body size on BVV using NCE-CT. We used a new indexing parameter that consisted of two parts: height and the difference between numerical values of height and body surface area (BSA). In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height. Aim We hypothesize that a novel indexation way allows for better discrimination of the increased bi-ventricular volume in overweight and obese patients. Method We retrospectively analyzed the CT data from 2466 patients with CAC scoring over the last 15 years. Among them 1606 women and 860 men with an average age of 64 ± 11 years (range 21-93). The fatless bi-ventricular volume was measured manually using commercial software on a dedicated workstation (Vitrea2). Values of the raw (measured, ml) BVV and BVV normalized for height, BSA, and the novel parameter i.e. [h+ (h-BSA)], were compared in patients taking into account body mass index (BMI) categories of normal weight (25% of patients), overweight (40%) and obese (35%). Results Overall, the measured BVV [ml] was significantly greater in males (414±97) than in females (297±66) (p<0.001). BVV decreased non-linearly from before 40ties to mid-60ties, and then remained nearly stable. In normal-weight males, the measured BVV (370±80ml) was greater than in normal-weight females (279±61ml) (p<0.001). In overweight males, the BVV was 411±89ml; in overweight females, the BVV reached 290±59ml (p<0.001). These differences were non-significantly different from the sample of patients with normal BMI. In obese patients, mean values significantly differed between males and females (442±106 vs 321±71 ml, p<0.001). As the absolute value of the BVV should be interpreted in the context of body habitus, normalization for height, BSA, and the novel index were used. The results of these examinations are given in the figure. Conclusions Commonly used methods of indexing the volumetric parameters of the ventricles, as well as the novel indexing approach showed similar results in patients with normal body weight. The proposed indexation allowed for discriminating the increase in BVV that is easy to overlook in overweight. The use of body surface area for volumetric normalization is misleading as it provides similar values in normal, overweight, and obese patients, and should therefore be avoided. We should consider whether ventricular size standards based on a study population under 50 years of age create reliable conditions for detecting ventricular enlargement at an older age.

Evidence that mitral and/or tricuspid regurgitation diminishes stroke volume increase during exercise

Abstract Background and Purpose The severity of heart failure can be evaluated by peak oxygen consumption (VO2). Cardiac output is one of the major essential factors to determine the VO2. Therefore, cardiac output increases linearly as the exercise intensity increases. However, in mitral regurgitation, effective stroke volume decreases due to some blood flowing back into the left atrium from the left ventricle. This reduction may compromise oxygen delivery to working muscles and diminish oxygen uptake. Peak VO2/HR is known to indicate the stroke volume at the peak exercise, but since c(A-V)O2 difference shows almost a similar change pattern during a ramp protocol, VO2/HR during the load is also reported to be an indicator of stroke volume (SV) at that work rate. However, there are no investigations that have examined the extent to which the increase in cardiac output during stress is affected by the severity of mitral regurgitation. Therefore, we investigated the influence of the degree of regurgitant volume in mitral regurgitation (MR) and tricuspid regurgitation (TR) affects the SV increasing response to exercise load. Additionally, we examined whether blunted SV increase influences on the peak VO2. Methods Among 525 patients who underwent cardiopulmonary exercise test (CPX) at our institution from January 2023 to October 2023, 518 patients (143 females, 375 males, mean age 65.2±15.0 years old) where precise analyses of CPX was possible. CPX was performed using breath-by-breath gas analysis, and an incremental load test (10watts/min) was administered until exhaustion. The rate of increase in VO2/HR per watt during an incremental loading (Δ(VO2/HR)/ΔWR) was used as an indicator of the degree of increase in SV. Typically, SV increases up to 60% of maximum load, around AT, after which it stops increasing and plateaus. Therefore, the slope of Δ(VO2/HR)/ΔWR was examined from the initiation of ramp loading to AT. The degree of reflux was evaluated by echocardiography and classified as none/trivial, mild and moderate/severe. The number of people in each group of None/trivial, mild, moderate/severe was, 392, 83, 30 for MR, and 416, 64, 24 for TR. Δ(VO2/HR)/ΔWR was evaluated for each degree of reflux, using ANOVA to determine whether there was a difference between groups. Results As shown in the Figure1, Δ(VO2/HR)/ΔWR decreased as the reflux flow rate increased for both MR and TR. Concurrently, peak VO2 also decreased in the moderate/severe group compared to the non/trivial-reflux group for both MR and TR (MR: 17.5±5.4 mL/min/kg vs. 14.9±3.5 mL/min/kg, TR: 17.2±5.3 mL/min/kg vs. 13.6±3.8 mL/min/kg). Conclusion The Δ(VO2/HR)/ΔWR obtained through CPX has been shown to be an index that can evaluate the severity of reflux. Additionally, it was also demonstrated that as regurgitation flow increased, true stroke volume decreases, which is correlated with a reduction in peak VO2.

Effect of rPET Content and Preform Heating/Cooling Conditions in the Stretch Blow Molding Process on Microcavitation and Solid-State Post-Condensation of vPET-rPET Blend: Part I—Research Methodology and Results

Polyethylene terephthalate (PET) is widely used in bottle production due to its cost-effectiveness and low environmental impact. The first part of this article describes the research and statistical analysis methodology of the influence of the virgin PET (vPET) and recycled PET (rPET) content in the vPET-rPET blend, as well as the preform heating/cooling conditions in the stretch blow molding (SBM) process on the microscopic bottle properties. Microscopic properties such as crystallinity, density, viscosity, relaxation degree of the amorphous phase, and microcavitation in PET were examined. This study reveals that microcavity and solid-state post-condensation effects occur during PET deformation in the SBM process. The increase in free volume, indicating microcavitation, was confirmed by measuring positron annihilation lifetime spectroscopy (PALS). PALS and density of the amorphous phase studies prove a reduction in the dimensions of the free volumes, with a simultaneous significant increase in their number and ellipsoidization. It can be associated with crystallite rotation in a temperature-dependent non-crystalline matrix. The occurrence of solid-state post-condensation effects was confirmed by measuring the intrinsic viscosity. The conclusions resulting from the analysis of the microstructure affecting the mechanical strength of the material were validated by pressure resistance tests of the bottles.

Electrical conductance study of Schiff base in different solvents and temperatures: DFT calculation

The electrical conductivities of the N-(2-chlorobenzylidene)benzylamine (NCB) as Schiff bases (SB) compound in water and methanol were studied in different temperatures, the mixtures of methanol and water studied in various percentages of methanol at 298 K. Initially, the relationship between equivalent conductivity and the square root of molar concentration was plotted to find electrolyte types using Kohlrausch equations. The plot indicates that NCB was weakly associated with water, methanol, and mixtures. Lee-Wheaton equation treated the experimental results of symmetrical electrolytes (1:1) to calculate the conductivity confines: equivalent conductance at infinite dilution Λₒ, association constant KA, and the main distance between ions in solution (R) at best-fit values of (ϬΛ). Thermodynamic quantities for the ion association reaction (∆Go, ∆Ho and ∆So) have been measured. Also, the theoretical calculation was used to optimize the energy of the molecule in the gas phase then measured many descriptors by using (AM1, PM3) then DFT. In addition, recalculated the optimization energy in water, and methanol. After theoretical calculation and analysis, it was found that the Λₒ value is related to the molecular volume of the system (molecules assembled in the solvent). As the molecular volume increases, the Λₒ value decreases due to association. KEY WORDS: Schiff bases, Electrical conductivities, Lee-Wheaton equation, Thermodynamic parameter, DFT Bull. Chem. Soc. Ethiop. 2025, 39(1), 177-187. DOI: https://dx.doi.org/10.4314/bcse.v39i1.15

Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta-Analysis.

Hypogonadotropic hypogonadism (HH) is a treatable cause of nonobstructive azoospermic male infertility. Gonadotropin treatment can successfully induce spermatogenesis in most patients, although comprehensive quantitative summary data on spermatogenic outcomes like those required to induce pregnancy is lacking in the literature. Systematic review and meta-analysis of outcomes related to male reproductive function following gonadotropin treatment. Our search strategy identified 41 studies encompassing 1673 patients with a mean age of 25 (± 5) years. Average sperm concentration achieved after a median of 18 months of gonadotropin treatment was 11.6 M/mL of ejaculate (95% CI 8.4-14.9). Sperm concentrations > 0, > 1, > 5, > 10 and > 20 M/mL were achieved by 78%, 55%, 36%, 24% and 15% of patients, respectively. Mean sperm output and the proportion of patients achieving all sperm thresholds were significantly greater following combined hCG/FSH treatment compared with hCG monotherapy. When compared by diagnosis, patients with congenital HH (CHH) had significantly lower mean sperm output compared with patients with hypopituitarism or mixed patient cohorts that did not differentiate between CHH and hypopituitarism. Treatment-related increases in testosterone and testicular volume (TV) were not different between hCG and combined hCG/FSH treated patients, although increases in TV were lower in men with CHH compared with those with hypopituitarism. Gonadotropin treatment successfully induced spermatogenesis in most men with pathological gonadotropin deficiency. Sperm outputs more consistent with those typically needed to induce a natural pregnancy were less commonly achieved. Despite similar effects on serum testosterone and TV, combined hCG/FSH appeared more efficacious than hCG alone at inducing spermatogenesis.

Phytochemical, Growth Performance and Haematological Indices of Aqueous Extract of Aphrodisiac Formulation against Acetaminophen Induced Hepatocyte Injuries in Wistar Rats

Zainacin Dadin duniya is known for its antioxidant and liver-protecting properties. This research assesses the phytochemical characteristics and impact of Zainacin Dadin Duniya water extract on growth and hematological factors in Wister rats with acetaminophen-induced liver damage. 60 female and 30 male rats were divided into five groups with each group consisting of 18 rats selected randomly. Group 1 received saline, group 2 received a liver medicine, group 3 received acetaminophen, group 4 received a daily dose of aqueous extract at 500 mg/kg, and group 5 received a daily dose of aqueous extract at 500 mg/kg along with 3 ml/day of acetaminophen, all administered for 28 days. The animals were weighed before and following the experiment. The hematological parameters were determined, including packed Cell Volume (PCV), Red blood Cell (RBC), Haemoglobin (Hb), Mean Cell Volume (MCV), and White Blood Cell (WBC). Findings indicated that the extract contains a considerable quantity of phytochemicals. Findings indicated a notable weight gain (P<0.05) in Groups 1, 2, 4, and 5 and weight reduction in Group 3. In Group 3, there was a significant decrease in erythrocyte counts (4.29%), packed cell volume (33.00%), and hemoglobin (6.17%) values, while there was an increase in leukocyte (9.62%) and Mean Cell Volume (54.33%) values compared to the other groups. The presence of acetaminophen in the treatment given to Group 3 rats could lead to a decline in their growth performance and trigger adverse reactions in their blood parameters, potentially impacting their overall development. The segment may act as a strong remedy for acetaminophen-induced hepatocytes by blocking those reactive oxygen species.

53 Clinical characteristics and outcomes of children hospitalized with RSV-associated acute respiratory infections

Abstract Background Respiratory syncytial virus (RSV) is one of the most common acute respiratory infections (ARI) in infants and young children. After the relaxation of COVID-19 pandemic restrictions, children’s hospitals worldwide experienced unprecedented volumes and severity in presentation of children admitted with ARIs, such as RSV. It is unknown whether the increase in volumes was also associated with changes in the typical demographic, severity and outcomes of patients with RSV infections. Objectives To describe sociodemographic characteristics, clinical presentation, management including diagnosis and disposition and clinical outcomes of children under the age of 18 years admitted to tertiary care paediatric hospital with RSV-associated ARI. Design/Methods Observational cohort of children and adolescents aged 0-18 years admitted to two large Canadian children’s hospitals between July 1, 2022 - December 31, 2022, who had microbiological evidence of RSV infection. Detailed clinical and demographic information were extracted, including admission and discharge diagnoses, diagnostic tests, viral and bacterial testing, interventions, and respiratory settings. Clinical outcomes and complications were collected, including length of hospital admission, paediatric intensive care unit (PICU) admission, need for invasive mechanical ventilation, disposition, and death. Results There were 455 patients admitted with an RSV infection, of which a third (35.0%, n=146) were transfers from other hospitals. Cases were 41.0% male and the median age was 1.22 years (interquartile range [IQR] 0.19-3.06). Nearly two-thirds of patients (62.0%, n=284) were younger than 2 years of age, 8.6% had a history of prematurity. One third (31.0%, n=142) of patients had at least one documented comorbid condition, the most common diagnosis was asthma (6.6%). In addition to RSV, 3.5% (n=16) of patients had a simultaneous bacterial pathogen identified. Most patients (73%, n=330) were only RSV positive, while 24% (n=109) had two pathogens identified. One quarter (25.9%) were admitted to the PICU. The median length of hospital stay was 3 days (IQR 2.00-5.00) and for those admitted to the PICU, nearly two thirds of patients (63.0%, n=75) were admitted for less than 4 days. 0 patients died. The most common discharge diagnosis in 61.0% of patients (n=279) was bronchiolitis. There were 56 patients (12.3%) who had an unscheduled return visit to the ED within 30 days of discharge with 23.0% (n=13) requiring readmission to the hospital. Conclusion There continues to be a substantial volume of hospitalizations secondary to RSV infection, predominantly in those <2 years of age, with a prominent diagnosis of bronchiolitis. A quarter of patients had notable severity requiring PICU admission.

Unveiling the hippocampal subfield changes across the Alzheimer's disease continuum: a systematic review of neuroimaging studies.

Studies exploring the hippocampal subfield atrophy in Alzheimer's disease (AD) have shown contradictory results. This review aims to disentangle such heterogeneity by investigating the dynamic changes of hippocampal subfields across the AD continuum. We systematically searched the PubMed and EMBASE databases for case-control studies. Selected studies included investigations of biomarker-based amyloid status and reported data on hippocampal subfield atrophy using advanced MRI techniques. Twelve studies were included. Despite high heterogeneity, a distinguishable pattern of vulnerability of hippocampal subfields can be recognized from the cognitively unimpaired phase to the dementia stage, shedding light on hippocampal changes with disease progression. Consistent findings revealed atrophy in the subiculum and presubiculum, along with a potential increase in volume in the cornu ammonis (CA) among the cognitively unimpaired group, a feature not observed in patients experiencing subjective cognitive decline. Atrophy in the subiculum, presubiculum, CA 1-4, and the dentate gyrus characterized the mild cognitive impairment stage, with a more pronounced severity in the progression to dementia.

Structural insights into the toxicity of type II ribosome inactivating proteins (RIPs): a molecular dynamics study

Ribosome Inactivating Proteins (RIPs) act by irreversibly depurinating the 28S rRNA ricin-sarcin loop (SRL) of the eukaryotic ribosome resulting in protein synthesis inhibition. In general, they consist of two variants: Type I which is single chained (∼30 kDa), and Type II, a more toxic variant which is a Type I N-glycosidase chain covalently linked to a lectin chain. These proteins are believed to play a pivotal role in defence mechanisms. Intriguingly, non-toxic variants of such toxic proteins do exist in nature. To explore their mode of action, in the present study we have selected three toxic (Ricin, Ebulin and HmRIP) as well as two non-toxic (BGSL and SGSL) RIPs and performed molecular docking and molecular dynamic simulations with the SRL loop. This study throws light on the structural stability and plasticity of the toxic and non-toxic RIP complexes. Furthermore, analysis of the active site cavity volume and binding free energy calculations reveal that the SRL, particularly the specific adenine (A4605), is relatively unstable in the case of non-toxic RIPs which is also supported by the free binding energy calculations, and the pocket size analysis indicates the abnormal increase in active site cavity volume of non-toxic RIPs with time. This first-of-its-kind comprehensive study of toxic and non-toxic RIPs gives insights about the mode of action and the dynamic nature of their interaction with the SRL loop. These observations will be helpful in the development of toxoids against RIPs and also in designing novel therapeutic approaches against human diseases.

The influence of spider news on online information-seeking.

Fear of spiders is a widespread condition often disproportionate to the actual danger spiders pose to humans. Likely rooted in evolutionary history, fear of spiders might also have a cultural component. Recent studies have shown that a significant fraction of spider-related media reports are misleading and sensationalistic. Information-seeking behaviours serve as common coping mechanisms for our fears and anxieties, yet the link between spider-related news stories and such behaviors remains unexplored.We hypothesize that media reports foster concern about spiders, resulting in an increased awareness of spiders and health issues associated with them. We extracted 1486 reports in English from a public database providing a content-analysis of spider-related online traditional media reports published between 2010-2020. We examined whether the volume of spider-related queries in Google Trends, Wikipedia, and iNaturalist increased in the week following the publication of each news story.Sensationalistic news stories were associated with a small, significant increase in search volumes, compared to non-sensationalistic ones. The search volume for "brown recluse" (Loxosceles reclusa), which are potentially dangerous spiders, was higher after the publication date of news related to human-spider encounters. There was a significant positive relationship between the number of spider-related news stories published in a given month and the traffic on target spider-related Wikipedia pages, especially so for the page on brown recluse spiders.Our results suggest that traditional media have a detectable impact on the behaviour of the general public towards spiders, supporting the hypothesis that the fear of spiders is perpetuated by culture. Additionally, our findings indicate that information-seeking behaviour is a common response to learn about spiders and potentially fact-check spurious claims found in sensationalised news. By recognizing the role of media in shaping attitudes towards spiders and acknowledging the benefits of accurate representation, we can lay the foundation for a more informed and harmonious relationship between humans and spiders.

An In vivo Pilot Study to Estimate the Swelling of the Aneurysm Wall Rabbit Model Generated with Pulsed Fluid Against the Aneurysm Wall.

This study addresses the critical issue of evaluating the risk of rupture of unruptured intracranial aneurysms (UIAs) through the assessment of the mechanical properties of the aneurysm wall. To achieve this, an original approach based on the development of an in vivo deformation device prototype (DDP) of the vascular wall is proposed. The DDP operates by pulsing a physiological fluid onto the vascular wall and measuring the resulting deformation using spectral photon counting computed tomography (SPCCT) imaging. In this preliminary study conducted on a rabbit animal model, an aneurysm was induced on the carotid artery, followed by deformation of the aneurysm sac wall using the DDP. The change in luminal volume of the aneurysm sac induced by the deformation of the vascular wall was then quantified. The initial experimental results demonstrated an increase in the luminal volume of the aneurysm sac in relation to the increased flow rate of the fluid pulsed by the DDP onto the arterial wall. Measurement of the pressure generated by the DDP in relation to the different flow rate values imposed by the pulsation system revealed experimental values of the same order of magnitude as dynamic blood pressure. Furthermore, theoretical pressure values on the deformed area, calculated using Euler's theorem, appeared to be correlated with experimental pressure measurements. This equivalence between theory and experiment is a key element in the use of the DDP for estimating the mechanical properties of the vascular wall, particularly for the use of finite element models to characterise the stress state of the deformed vascular wall. This preliminary work thus presents a novel, innovative, and promising approach for the evaluation and management of the risk of rupture of unruptured intracranial aneurysms.

Unveiling the causal nexus between Saudi’s seaborne trade and economy: evidence from an ARDL model

An economy’s primary objective is to foster high economic growth, ultimately enhancing the well-being of its citizens. Recent economic strategies have increasingly emphasized trade-oriented policies to achieve this goal. This study delves into the nexus between Saudi seaborne trade (measured in tons) and gross domestic product (GDP), aiming to determine any causal relationship between these economic variables. Using datasets from the Saudi Central Bank and the General Authority of Statistics, this research employs rigorous unit root, cointegration, and causality tests to find the intricate interplay between trade and economic growth in Saudi Arabia. The empirical analysis highlights a robust long-term relationship between Saudi GDP and seaborne trade, suggesting cointegration. Specifically, the findings reveal a significant impact of economic growth on seaborne trade, as indicated by a trade elasticity of 1.08, which implies that changes in GDP yield a substantial shift in trade. For instance, a 1% increase in GDP corresponds to an approximate 1.08% increase in trade volume. The error correction mechanism also illustrates the dynamic adjustment process: deviations of Saudi seaborne trade and economic growth from equilibrium are corrected by 61% and 43%, in the subsequent year. Furthermore, Granger causality tests unveil bidirectional causality between GDP and trade, elucidating that economic growth changes precede trade volume alterations and vice versa. Thus, fostering international trade not only stimulates income but also bolsters the domestic economy of Saudi Arabia.

Optimal Water and Nitrogen Regimes Increased Fruit Yield and Water Use Efficiency by Improving Root Characteristics of Drip-Fertigated Greenhouse Tomato (Solanum lycopersicum L.)

The growth of root system directly affects the absorption and utilization of soil water and nitrogen, and understanding the responses of root characteristics to water and nitrogen regimes is thus crucial for optimizing water and nitrogen management. The root characteristics of each soil layer, i.e., root length, root surface area, and root volume, as well as fruit yield and water use efficiency of greenhouse tomato under drip fertigation in response to different irrigation levels and nitrogen rates were explored in northwest China. There were four irrigation levels, i.e., 50% ETC (W1), 75% ETC (W2), 100% ETC (W3), and 125% ETC (W4), where ETC is the crop evapotranspiration, and four nitrogen rates, i.e., 0 kg ha−1 (N1), 150 kg ha−1 (N2), 250 kg ha−1 (N3), and 350 kg ha−1 (N4). The results showed that reasonable irrigation and nitrogen regimes (W3N3) significantly increased fruit yield by 31.64% and root length, root surface area, and root volume by 45.03%, 61.24%, and 148.21% compare to W3N1, respectively. The promoting effect of increasing irrigation level on root characteristics increased with soil depth and had the greatest increases in root volume by 27.07%, 123.43%, and 211.47% for the 0–10, 10–20, and 20–30 cm soil layers, respectively. In addition, reducing irrigation level significantly increased the percentages of roots in the top soil by 29.71%, 26.77%, and 18.53% for root length, root surface area, and root volume, respectively. The reasonable nitrogen rate (N3) significantly increased fruit yield by 41.11%, water use efficiency by 34.42%, and root length, root surface area, and root volume by 40.42%, 41.44%, and 112.76%, respectively. The over-application of nitrogen (N4) reduced root characteristics of all soil layers, fruit yield, and water use efficiency. The promoting effect of increasing nitrogen rate on root length of each soil layer decreased with soil depth, by 71.01%, 48.96%, and 15.71% for 0–10, 10–20, and 20–30 cm soil layers, respectively. Irrigation level was the main factor dominating the root growth of each soil layer. The correlation analysis showed that fruit yield had significantly positive correlations with root characteristics in all soil layers, while water use efficiency had significantly positive correlations with the percentages of root length and root surface area in the 0–10 cm soil layer. In conclusion, rational water and nitrogen regimes achieved better fruit yield by promoting root growth of greenhouse tomato, and the water use efficiency of greenhouse tomato was improved by increasing the root percentage in the topsoil layer to alleviate the adverse effects under water stress conditions. This study reveals how irrigation volume and nitrogen application can enhance tomato yield and water use efficiency by regulating root characteristics and vertical root distribution, providing support for understanding the response of root systems to changes in soil water and nitrogen conditions.

Effects of Bacterial Lysates on TLRs/NF-κB Pathway, Immune Function, and Prognosis in Children with Pulmonary Infection Caused by Streptococcus pneumoniae

Background: Bacterial lysates, as immunomodulators, may play a role in regulating the host immune response. Objectives: This study aimed to investigate the effects of bacterial lysates OM85-BV in treating pulmonary infections caused by Streptococcus pneumoniae in children. Methods: A total of 120 children with S. pneumoniae pulmonary infection were divided into two groups: The control group and the OM85-BV group, with a 1: 1 ratio. The control group received intravenous mezlocillin at 100 mL/kg/d, while the OM85-BV group, in addition to mezlocillin, received OM85-BV orally at 3.5 mg per dose. The improvement of clinical symptoms and pulmonary function indexes—including respiratory rate, tidal volume, volume to peak expiratory flow as a proportion of exhaled volume, and time to peak tidal expiratory flow as a proportion of expiratory time—were compared. Additionally, levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), T lymphocyte subsets, and immunoglobulins in serum were analyzed. Results: Compared to the control group, the OM85-BV group showed a significant decrease in respiratory rate and an increase in tidal volume, volume to peak expiratory flow, and time to peak tidal expiratory flow (P < 0.05 for all). The OM85-BV group also had significantly lower levels of serum inflammatory factors such as CRP, TNF-α, IL-6, and sIL-2R. In terms of immune function, the OM85-BV group showed increased levels of T lymphocyte subsets CD3+, CD4+, and CD4+/CD8+ ratios, with a decrease in CD8+, as well as elevated serum IgA and IgG levels. The total effective rate of treatment in the OM85-BV group was significantly higher than in the control group (P < 0.05). Conclusions: The addition of OM85-BV to the treatment of S. pneumoniae pulmonary infection in children significantly improves clinical symptoms, lung function, and immune function, while reducing the inflammatory response. OM85-BV appears to inhibit the activation of the toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) pathway.

Early crack resistance and life cycle assessment of seawater-mixed sintered sludge cement paste

Due to the accelerating effect of chloride and sulfate on the hydration of clinker, seawater-mixed cement (SC) paste is more prone to brittle cracking. Herein, this research systematically investigates the early crack resistance of seawater-mixed sintered sludge cement (SSSC) paste based on splitting tensile test and restrained squared eccentric ring test. The microstructure characteristics characterized by mercury intrusion porosimetry and scanning electron microscopy are combined to reveal the enhancement mechanism of sintered sludge ash (SSA) on SC paste, and a life cycle assessment is conducted around its carbon footprint. The results indicate that the SSA incorporation causes a continuous increase of 24.4 % in the splitting tensile strength of SSSC paste. Meanwhile, the digital image correlation technology accurately captures the strain and displacement fields composed of crack propagation, which tends to be symmetrically distributed and reduces the crack width by 30 %. During the inhomogeneous restrained shrinkage process, as the SSA increases, the crack deviation of the SSSC paste first magnifies and then reduces, the crack width decreases, and the cracking time extends. The pozzolanic activity of SSA is more active in SC paste, which significantly promotes the secondary accumulation of C-S-H and the increase of gel pore volume. This effectively reduces the risk of brittle cracking caused by uneven distribution of paste stiffness due to hydration acceleration during seawater mixing. In addition, replacing 50 % cement with SSA only results in a total of 4.1 % carbon emissions in SSSC paste and a 47.8 % reduction in global warming potential from sludge transportation to activation treatment, demonstrating significant environmental advantages.

New risk factors and predictions of the development of retinal vein occlusion after cardiac surgeries with the use of artificial circulation

Background. Cardiovascular diseases are one of the risk factors for the development of retinal vein occlusion (RVO). Cardiac interventions with artificial circulation (AC) can be associated with perioperative complications, including retinal vessel occlusion. The actual task of modern ophthalmology is to determine the frequency of retinal vessel occlusions, clinical features, risk factors, the role of markers of inflammation and endothelial dysfunction in RVO in patients with cardiovascular diseases after surgeries with artificial circulation. The purpose of the study was to investigate new risk factors and predict the development of retinal vein occlusions after cardiac surgeries using artificial circulation. Materials and methods. Three hundred and ninety-four patients (638 eyes) were under observation. Of them, 220 people (405 eyes) had cardiovascular diseases and underwent heart surgeries with the use of AC. In these patients, we determined the nature, frequency and features of the development and clinical course of RVO after cardiac surgery with AC in the early and late periods of observation (3 and 6 months). Also, a study was conducted of 174 patients (233 eyes) with cardiovascular diseases who underwent cardiac surgeries with AC, and the serum levels of markers of inflammation (IL-6 and IL-8) and endothelial dysfunction (VE-cadherin) were determined before and after operations depending on the time of RVO occurrence. The main group included 126 patients (137 eyes) who were diagnosed with occlusion of the central retinal vein (CRV) or its branches after surgery with AC; the comparison group — 43 patients (86 eyes) who did not have retinal vein occlusion during the entire observation period; the control group — 5 patients (10 eyes) who had the same degree and duration of the underlying disease, indications for surgery with AC, but were examined before the operation, and within 180 days after it, and did not have RVO. The patients were examined by an ophthalmologist 2, 7, 30, 60, 90 and 180 days after cardiac surgery. The content of IL-6, IL-8 and VE-cadherin in blood serum was determined by the enzyme immunoassay (Bender MedSystems, Austria). Statistical data were processed using the Statistica 10 program (StatSoft Inc., USA), regression analysis was performed with the help of the GLZ software package. Results. As a result of the research, it was found that the frequency of retinal vein occlusions after cardiac surgeries with the use of artificial circulation was 0.99 % on the 2nd day, 3.95 % on the 7th day, 10.2 % after 3 months, 1.4 % after 6 months. The conducted discriminant analysis showed that the type of occlusion was determined by age, lower visual acuity, and the order of occlusion of the CRV branches. An increase in the macular volume of the retina was also significant, reflecting the development of macular edema. The regression model for predicting the type of occlusion based on visual acuity, the order of occlusion of the CRV branches and age had a prediction accuracy of 82.5 %. Cardiac surgeries with the use of AC caused an increase in interleukin content in the early period (IL-6 on days 2 and 7, and IL-8 — up to day 30), while the content of VE-cadherin was slightly increased during almost the entire observation period. In the presence of RVO, IL-6 content was significantly higher at all stages of occlusion development, IL-8 content — up to 30 days, and VE-cadherin content — mostly after 7 days. Regression analysis showed that after 1–2 days, the occurrence of RVO was directly related to the content of IL-6 and IL-8 in the blood, on days 3–7 — to the content of only IL-8, on days 8–30 — to the content of all markers, and later — to the content of IL-6 and VE-cadherin. The prediction accuracy for the presence or absence of RVO in the corresponding term according to the calculated regression models is at least 78 % (p < 0.001), which proves the influence of markers on the development of RVO. Conclusions. The conducted study shows the importance of acute inflammation and endothelial dysfunction in the occurrence of RVO when using AC, which justifies the use of preventive measures in the early stages of limiting the activity of the inflammatory process, in the later stages — preventing the development of endothelial dysfunction.