Dense Tissue Research Articles

Low conduction velocity is a key factor for localisation of reentrant drivers for atrial fibrillation

Abstract Background Atrial Fibrillation (AF) is a prevalent cardiac arrhythmia globally, associated with heightened risks of stroke, dementia, and heart failure. Catheter ablation, the sole curative therapy for AF, yields suboptimal success rates for persistent AF cases. Understanding the mechanisms and dynamics of AF remains challenging, hindering treatment advancements. Novel ablation strategies aimed at targeting substrates harbouring AF reentrant drivers (RD), such as low-voltage ablation and rotor-based ablation, have yet to demonstrate superiority over the gold standard ablation strategy – pulmonary vein isolation. Purpose The purpose of the study is to integrate in-silico 3D left atrial (LA) simulations and explainable artificial intelligence (AI) to pinpoint key factors for RD localisation in persistent AF, aiming to improve the mechanistic understanding of AF and help develop a more effective ablation strategy. Methods 3D LA models were derived from magnetic resonance images of 41 patients and combined with atrial cell electrophysiology models. Persistent AF was initiated in each patient-specific LA model with fast pacing, and five functional features (action potential duration (APD), conduction velocity (CV), wavelength, APD spatial gradient, CV spatial gradient, and wavelength spatial gradient) and three structural features (fibrotic density, fibrotic entropy, and image intensity ratio) were evaluated. A random forest AI model was trained to classify phase singularities corresponding to the RDs (PS-RD) in five distinct tissue classes (total LA tissue, healthy tissue, fibrotic border zone, dense fibrotic tissue, and PS-RD tissue) based on the functional and structural features. Shapley additive explanations (SHAP) analysis was then used to find the most influential feature in the AI model’s decision process. Results Simulations of the patient-specific LA models revealed that RDs were typically localised in regions with the lowest atrial CV, which often coincided with patches of dense fibrotic tissue. In a five-fold cross-validation, the random forest AI model achieved high accuracy in classifying PS-RD regions: a mean ROC AUC of 0.99 ± 0.010, a mean F1 score of 0.86 ± 0.034, a mean recall of 0.95 ± 0.058, and a mean precision score of 0.79 ± 0.085. The further SHAP analysis revealed that low CV was the key determinant in classifying the PS-RD regions. Conclusion Our study combined AF computational modelling and explainable AI to identify the key factors in RD localisation. Both the computational and AI models concluded that low CV was the most important determinant in localising RDs. These findings provide mechanistic evidence for the efficacy of ablation strategies that target low CV atrial areas for persistent AF patients.

In-vitro and in-vivo assessment of the bactericidal potential of peracetic acid and hydrogen peroxide disinfectants against A. hydrophila infection in Nile tilapia and their effect on water quality indices and fish stress biomarkers

This study aimed to assess the in vitro and in vivo disinfectant potential of peracetic acid (PAA) (1 mg/L) and hydrogen peroxide (H2O2) (20 mg/L) on the physicochemical and microbiological water quality parameters of fish aquaria, the microbial density of Nile tilapia muscular tissue, fish hepatic cortisol levels, and antioxidant biomarkers. In vitro, PAA and H2O2 reduced A. hydrophila colony viability by 5 log units after 30 and 5 min of contact time, respectively. PAA and H2O2 were added to aquaria water twice a week for the three-week experiment. Increased fish escape reflexes were observed only in the PAA group, which returned to normal within 10 min. No mortalities were reported in either the PAA or H2O2 groups. An in vivo experimental challenge with a pathogenic strain of A. hydrophila revealed a 20% reduction in mortality in the PAA group, with no mortalities in the H2O2 group. Cortisol levels and antioxidant markers were measured to assess the impact of PAA and H2O2 on fish health. Cortisol levels in the PAA and H2O2 groups were significantly higher than in the control group after disinfectant exposure, but they progressively returned to normal. A significant reduction in superoxide dismutase (SOD) and catalase (CAT) activity, along with considerably higher glutathione peroxidase (GPx) and malondialdehyde (MDA) enzymatic activity, was observed in the PAA and H2O2 groups compared to the control group. A substantial increase in total antioxidant capacity (TAC) was recorded in the PAA group. Physicochemical analyses revealed reduced pH and increased dissolved oxygen levels in the PAA and H2O2 groups. Microbiological analyses showed a significant reduction in bacterial density in water by 64% and 76% after 30 min of exposure to PAA and H2O2, respectively, with a non-significant increase in microbial count after bacterial challenge. Additionally, aerobic bacterial count, Aeromonas spp., and psychotropic bacterial count in fish muscle showed a significant reduction in the H2O2 group compared to the PAA and control groups before and after infection. The study concludes that regular application of PAA and H2O2 can temporarily reduce bacterial load in aquaria and fish muscle, regulate stress responses, and improve fish health by reducing A. hydrophila-induced infections and improving survival.

Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study

Abstract Background Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-). Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). Methods This cross-sectional study compared PLWH aged 35-55yrs (diagnosed >10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.). Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.) Results 98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66). 79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. >50% luminal stenosis) and none in the control group. (p=0.49) The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=<0.05). Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI. Conclusion PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction

Abstract Background Heart failure (HF) with improved ejection fraction (EF, HFimpEF) gains increasing attention as a distinct HF subtype, characterized by left ventricular reverse remodeling and myocardial recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. Methods A total of 203 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute EF improvement ≥10% and (2) a second EF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. Results During a median follow-up of 8.6 (4.9~13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (126.03 ± 57.71 cm3 vs 182.74 ± 82.99 cm3 , P< 0.001) and higher EAT density (-74.92 ± 6.84 HU vs -78.76 ± 6.28 HU, P< 0.001) both in ischemic and non-ischemic HF patients. EAT density was inversely correlated with EAT volume (r= -0.33, P< 0.001). Multivariate analysis showed lower EAT volume (OR: 0.881 [95% CI 0.821~0.939]) and higher density (OR: 2.354 [95% CI 1.314~4.415]) were both independently associated with the incidence of HFimpEF, after adjusting for conventional risk factors, pharmacological therapies and baseline anthropometric parameters including body mass index. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. Conclusions This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Grating-based phase-contrast computed tomography for breast tissue at an inverse compton source

The introduction of mammography screening programs has significantly reduced breast cancer mortality rates. Nevertheless, some lesions remain undetected, especially in dense breast tissue. Studies have shown that phase-contrast imaging can improve breast cancer diagnosis by increasing soft tissue contrast. Furthermore, grating-based phase-contrast imaging enables the simultaneous acquisition of absorption, phase-contrast, and scattering, so-called dark-field images. The latter allows the classification of microcalcifications. In addition, breast computed tomography (BCT) systems can identify and discriminate overlapping but clinically relevant structures. This study investigates the benefit of combining grating-based phase-contrast with BCT. We explore the potential of grating-based phase-contrast breast computed tomography (gbpc-BCT) with a breast phantom and a freshly dissected fibroadenoma. Improved image contrast could be achieved with radiation doses comparable to those used in clinical BCT.

The influence of storage conditions on the dynamics of physicochemical markers of champignon (Agaricus bisporus) quality

Agaricus bisporus are the most common cultivated mushrooms. Champignons are a source of chitin, glycogen and minerals, and also have attractive organoleptic properties. Physicochemical and organoleptic characteristics of fresh Agaricus bisporus undergo significant changes during storage due to moisture transpiration, respiration and oxidative processes. The purpose of this work was to study the influence of storage conditions of cultivated champignons with unstained cap epithelium on the dynamics of their physicochemical parameters, as well as its relationship with changes in organoleptic parameters. The mushrooms were stored in refrigerated chambers at a constant temperature of +2 °C and +6 °C in polypropylene trays placed in bags made of biaxially oriented polypropylene (BOPP) perforated film and polyethylene (PE) film without perforation. Under all storage conditions studied, the nature of the dynamics of physicochemical parameters was close to linear (with the exception of the humidity of fruiting bodies when stored in PE film) — the calculated values of the Pearson correlation coefficient ranged from 0.67 to 0.97. Using two-factor analysis of variance, the influence of both packaging material and storage temperature on the dynamics of soluble solids content and mushroom tissue density was confirmed. When stored in PE film without perforation, a more intense negative dynamics of these criteria was observed compared to storage in perforated BOPP film. The identified difference is explained by the fact that in packaging made of PE film without perforation, conditions for anaerobic respiration were formed by the end of storage — the oxygen content decreased from 20.5% to 1.5–2.5%, which also contributed to the activation of decay processes. With increasing storage temperature, a more intense change in physicochemical parameters was observed, which was associated with an increase in metabolic rate. The relationship between the dynamics of all studied physicochemical quality markers and the dynamics of sensory assessments (with the exception of the marker "content of soluble solids" when stored in a perforated BOPP film at a temperature of 2 °C) has been statistically confirmed. Based on the results of the studies, the applicability of the criteria “humidity of fruiting bodies”, “content of soluble dry substances” and “density of fungal tissue” as markers for assessing the quality of cultivated Agaricus bisporus was confirmed.

Invasive plants and their root traits are linked to the homogenization of soil microbial communities across the United States

Although the impacts of invasive plants on soil ecosystems are widespread, the role and impacts of invader root traits in structuring microbial communities remain poorly understood. Here, we present a macroecological study investigating how plant invaders and their root traits affect soil microbial communities, spanning data from 377 unique plots across the United States sampled multiple times, totaling 632 sampling events and 94 invasive plant species. We found that native and invasive plants harbor different root traits on average, with invasive plants possessing higher specific root lengths and native plants having higher root tissue density. We also show that soil microbial communities experiencing heavy plant invasions were more similar to each other in composition across ecosystem types and geographical regions than plots with higher proportions of native plants, which displayed highly variable microbial communities across the continent. Root traits of invasive plants in highly invaded plots explained two times more variation in microbial composition than native plants. This work represents an important step toward understanding macroscale and cross-scale patterns of the relationship between plant invasions, root traits, and soil microbial composition. Our findings provide insights into how invasive plants may impact ecosystem functioning at the macroscale via their homogenizing influence on microbial communities.

Gonadotropin-releasing hormone and organs of the immune system

As a result of a literature search, the physiological aspects of the gonadotropin-releasing hormone (GnRH) influence on immune organs, such as red bone marrow, thymus, spleen and lymph nodes, were considered. The use of GnRH drugs leads to the replacement of red bone marrow with yellow one with an increase in the content of lymphoid and myeloid progenitor cells. In parallel, processes of osteoporosis occur due to increased bone resorption with corresponding changes in calcium metabolism and a decrease in the density of various bone tissues. At the same time, there are papers reporting no effect of GnRH on bone density and changes in calcium metabolism. GnRH acts on the thymus during embryonic development, and in postnatal ontogenesis, and during inflammation and age-related involution processes. Not only GnRH causes changes in the thymus; the thymus may also influence on the GnRH system. A direct effect of GnRH on spleen cells had not been detected, but the weight of the organ changed as a result of active immunization against GnRH in experiment. Unfortunately, very few articles demonstrate the physiological mechanisms of immunomodulation in such conditions. In any case, the obvious insufficiency and contradictory of publications on each aspect of GnRH effects indicates that they have been poorly studied, and it’s advisabile of further continuing not only applied research, but also fundamental investigations, due to its possible high prospects for creating immune control systems.

IgG4-Related Disease Involving the Ear: A Case Report.

IgG4-related disease is a chronic inflammatory disease with widespread clinical presentation. It mimics various malignant, infectious, and inflammatory conditions, leading to confusion in diagnosis and management. Otological manifestations, though relatively rare, can lead to significant complications. A 45-year-old male with a recent history of ventilation tube placement in the right ear presented with a sensation of imbalance associated with profound hearing loss. He was managed in line of acute otitis media with labyrinthitis with steroids and antibiotics and removal of the ventilation tube. He returned in one week and presented with right-sided lower motor neuron-type facial paresis. Computed tomography images of the temporal bone showed a soft tissue density lesion in the right middle ear cavity extending to the mastoid antrum. He underwent a right cortical mastoidectomy with decompression of the facial nerve. Histopathology and immunohistochemistry of granulation tissues from the middle ear and the mastoid revealed evidence suggestive of probable IgG4 disease. IgG4-related disease is a relatively new entity, and its pathogenesis has not been properly understood. IgG4 subclass has been involved in this disease resulting in fibro-inflammatory conditions leading to tumor-like masses or fibrosis of the affected organs. Treatment includes glucocorticoids and immunosuppressant medications.

Correlation of CT measurements of total body gas volume and hounsfield units with post-mortem interval

Accurate estimation of the post-mortem interval (PMI) may be a matter of crucial importance in forensic investigations.A preliminary investigation to assess whether longitudinal changes in organ Hounsfield units (HU) and total body gas volume (TBGV), as measured from serial PMCT scans, correlate with postmortem interval (PMI).: Eight euthanised lambs each had five whole body CT scans performed over seven days and measurements were taken from the brain, heart, lungs, liver, kidneys and spleen. HU tissue density was measured directly from the PMCT images, while TBGV was calculated using ImageJ software. A random effect model was fitted with the subject fitted as a random intercept. Ethical and Animal Welfare approval was obtained. : The average increase in TBGV was 422 ml/Kg with a change of 77 ml/Kg per day. For each additional post-mortem day, the HU of the brain, heart, lung, liver and spleen decreased by per day since death, while HU for the kidneys increased by day since death. Expect for the kidney where it increased, there was clear and progressive decrease in tissue densities and for all organs there was an increase in TBGV over time. However, the overlap in values between cases indicates that more work is required before either HU or TBGV can be developed as non-invasive methods to reliably determine time of death in humans.

Multi-modal classification of breast cancer lesions in Digital Mammography and contrast enhanced spectral mammography images

Breast cancer ranks as the second most prevalent cancer in women, recognized as one of the most dangerous types of cancer, and is on the rise globally. Regular screenings are essential for early-stage treatment. Digital mammography (DM) is the most recognized and widely used technique for breast cancer screening. Contrast-Enhanced Spectral Mammography (CESM or CM) is used in conjunction with DM to detect and identify hidden abnormalities, particularly in dense breast tissue where DM alone might not be as effective. In this work, we explore the effectiveness of each modality (CM, DM, or both) in detecting breast cancer lesions using deep learning methods. We introduce an architecture for detecting and classifying breast cancer lesions in DM and CM images in Craniocaudal (CC) and Mediolateral Oblique (MLO) views. The proposed architecture (JointNet) consists of a convolution module for extracting local features, a transformer module for extracting long-range features, and a feature fusion layer to fuse the local features, global features, and global features weighted based on the local ones. This significantly enhances the accuracy of classifying DM and CM images into normal or abnormal categories and lesion classification into benign or malignant. Using our architecture as a backbone, three lesion classification pipelines are introduced that utilize attention mechanisms focused on lesion shape, texture, and overall breast texture, examining the critical features for effective lesion classification. The results demonstrate that our proposed methods outperform their components in classifying images as normal or abnormal and mitigate the limitations of independently using the transformer module or the convolution module. An ensemble model is also introduced to explore the effect of each modality and each view to increase our baseline architecture's accuracy. The results demonstrate superior performance compared with other similar works. The best performance on DM images was achieved with the semi-automatic AOL Lesion Classification Pipeline, yielding an accuracy of 98.85 %, AUROC of 0.9965, F1-score of 98.85 %, precision of 98.85 %, and specificity of 98.85 %. For CM images, the highest results were obtained using the automatic AOL Lesion Classification Pipeline, with an accuracy of 97.47 %, AUROC of 0.9771, F1-score of 97.34 %, precision of 94.45 %, and specificity of 97.23 %. The semi-automatic ensemble AOL Classification Pipeline provided the best overall performance when using both DM and CM images, with an accuracy of 94.74 %, F1-score of 97.67 %, specificity of 93.75 %, and sensitivity of 95.45 %. Furthermore, we explore the comparative effectiveness of CM and DM images in deep learning models, indicating that while CM images offer clearer insights to the human eye, our model trained on DM images yields better results using Attention on Lesion (AOL) techniques. The research also suggests a multimodal approach using both DM and CM images and ensemble learning could provide more robust classification outcomes.

Evaluation of vascular invasion in pancreatic head tumors and its impact on radical surgical treatment

Objective. To evaluate the informativeness and sensitivity of radiological criteria for vascular invasion in pancreatic head tumors in comparison with intraoperative data and results of routine pathological examination. Materials and methods. The study included 98 patients with ductal adenocarcinoma of the pancreatic head with suspected venous invasion and spread of tumor growth along the vessels of the portomesenteric axis, who were operated on at the Department of Pancreatic and Bile Duct Surgery of the National Research Center of Surgery and Transplantation named after O. A. Shalimov in the period from 2019 to 2023. Group 1 included 51 (52.0%) patients who underwent radical surgery with resection of the superior mesenteric/hepatic portal vein and extended lymph and neurodissection, and group 2 included 47 (48.0%) patients who had positive vascular margins of pancreatic resection according to routine pathological examination. Diagnostic criteria for vascular alterations were developed. A comparative analysis of the informativeness of the developed criteria and the results of a routine pathological examination was performed. The edges of the pancreatic resection were evaluated, including the neck of the gland, common bile duct, duodenum/gastric duct, and the bed of the superior mesenteric/hepatic portal vein and superior mesenteric artery separately. R1 status was defined as the presence of tumor cells at a distance of less than 1 mm to the resection margin. Results. According to the criteria of the National Comprehensive Cancer Network (NCCN) 2023.2, 61 (62.2%) patients had a marginally resectable stage of ductal adenocarcinoma of the pancreatic head and tumor contact with the superior mesenteric/hepatic veins according to multislice computed tomography of the abdominal cavity. In group 1, there were 36 (70.6%) such patients, in group 2 – 25 (53.2%). According to the proposed radiologic criteria for vascular invasion, tumor contact with the superior mesenteric/hepatic portal veins was suspected in 76 (77.6%) patients, which is higher than in the standard approach. Determination of vascular alterations according to the results of our study is a more reliable method for diagnosing invasion of the superior mesenteric/hepatic portal vein (χ2 = 5.46, p = 0.019) and predicting the performance of radical surgery, including vascular resection. Conclusions. The proposed criteria for the radiological diagnosis of vascular invasion at the preoperative stage increased the sensitivity of this method from 62.2 to 77.6%. The most frequent radiological signs of vascular alteration are vascular wall irregularity (47.7%) and parapancreatic tissue density (62.5%). In the presence of any of the radiological signs of vascular alteration, resection of the affected area of the superior mesenteric/hepatic portal vein with extended lymph and neurodissection is indicated, which allows a statistically significant increase in the number of R0 resections.

Multiple pulmonary hamartomas with malignant transformation of a giant pulmonary hamartomas: a case report

Pulmonary hamartomas are the most common benign tumors of the lung, typically solitary with a diameter≤4 cm, and rarely undergo malignant transformation. We reported a case of multiple pulmonary hamartomas with malignant transformation of a giant pulmonary hamartoma (approximately 10 cm×12 cm in size). The patient was a 61-year-old female who sought medical attention for the discovery of multiple lesions in the right lung during a routine examination. Computed tomography revealed multiple soft tissue density lesions in the right lung. Surgical resection was performed to remove the lower lobe of the right lung and the lesion located in the posterior segment of the right upper lobe. The pathological results indicated that the right lower lobe lesion had undergone malignant transformation to a high-grade chondrosarcoma originating from a hamartoma, while the right upper lobe lesion remained a hamartoma. By analyzing this case together with the relevant literature, we aimed to emphasize the need for clinical awareness of the malignant potential of pulmonary hamartomas.

Silver loaded functionalized calix [4]arene nanofibers and evaluation in burn wound healing

Burn treatments with gene therapy and healing factors requires highly cost techniques. Instead, topical formulations including plant extract or pharmaceuticals are offered for wound-healing effect. However, these have low water solubility and cannot uptake into cells sufficiently. To overcome disadvantages, new effective treatment approaches should have been accessible. This study aimed to develop nanofiber-based wound coverings using four different Ag(I)-calixarene derivatives. Their nanofibers were produced by the electrospin method, and evaluated in vivo in rats with a second-degree burn model. Biochemical analysis has been maintained to exmine the effects of formulations on such as growth factors and some cytokines that are effective in wound healing process. In addition, histopathological analyzes has been performed to evaluate the presence and density of granulation tissue, inflammation, epithelial thickness and fibrosis. All data were compared with a commercial topical, silver sulfadiazine, whose usage is limited due to various disadvantages in the treatment processes of burn wounds. In this study, four different calixarene derivatives were synthesized their nanofibers were produced by the electrospin method, and their effectiveness was evaluated in vivo in rats with a second-degree burn model. Then, various biochemical and histopathological analyses were done to elucidate the possible wound-healing mechanism. When considering both pathological and biochemical data, the nanofibers of CLX-SAMD-Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(Sulfadiazine)‐26,28‐propylcalix (Xie and Unser, 2013) [4]arene - Ag) and CLX-MORF- Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(3-Morpholinopropil)‐26,28‐dihydroxycalix (Xie and Unser, 2013) [4]arene-Ag) were found to be more effective than silver sulfadiazine -silver content application, also known as traditional burn treatment for wound healing.

Aerobic Exercise Prevents High-Fat-Diet-Induced Adipose Tissue Dysfunction in Male Mice

Background/Objectives: This study aimed to assess the effect of aerobic exercise on capillary density and vascular smooth muscle cell (VSMC) phenotype in the visceral and subcutaneous adipose tissue of high-fat-diet (HFD) mice in order to understand the mechanisms underlying improvements in insulin resistance (IR) and chronic inflammation in adipose tissue (AT). Methods: Male C57BL/6J mice were divided into HFD and normal diet groups for 12 weeks and then further split into sedentary and aerobic exercise subgroups for an additional 8 weeks. Various parameters including body weight, fat weight, blood glucose, lipid profile, insulin levels, glucose tolerance, and inflammatory cytokines were evaluated. Results: Aerobic exercise reduced HFD-induced weight gain, IR, and improved lipid profiles. HFD had a minimal effect on inflammatory cytokines except in visceral adipose tissue (VAT). IR was associated with capillary density in subcutaneous adipose tissue (SAT) and VSMC phenotype in VAT. Aerobic exercise promoted anti-inflammatory responses in VAT, correlating with VSMC phenotype in this tissue. Conclusions: Aerobic exercise can alleviate HFD-induced IR and inflammation through the modulation of VSMC phenotype in AT.

Traits associated with the conservation gradient are the strongest predictors of early‐stage fine root decomposition rates

Abstract Fine root traits span two independent axes of variation, the conservation and collaboration axes, which define the root economic space (RES). However, whether early‐stage fine root decomposition rates (quantified as proportion mass loss, i.e. pml) are more strongly related to collaboration or conservation traits remains unclear. We studied 63 tree species in New Zealand's temperate rain forest. We determined the phylogenetic signal in pml and fine root traits, conducted phylogenetic principal component analysis and used phylogenetic generalized least squares to determine which traits are most strongly related to pml. Root decomposition exhibited a high phylogenetic signal and was more strongly related to the conservation than the collaboration axis. Root tissue density (RTD) was negatively correlated and root nitrogen (RN) was positively correlated with pml. Root diameter was positively yet weakly correlated with pml, but specific root length was uncorrelated with pml. The lignin‐to‐N ratio and root cellulose were the strongest predictors of pml. Synthesis: Early‐stage fine root decomposition is most strongly driven by tissue quality traits, such as root nitrogen, tissue density and lignin‐to‐N ratio, which all align with the conservation axis of the root economics space. However, root diameter plays a weak yet undeniable role in early‐stage fine root decomposition. Some thick‐rooted species decomposed faster, possibly due to the higher quality cortical tissue. Thin‐rooted species decomposed slower, possibly because of their higher cellulose concentration that maintains the structural integrity of small diameter roots. Relationships between decomposition and other traits that align with the collaboration gradient deserve further study across the phylogeny of vascular plants.

Anatomical Responses of Two Species under Controlled Water Restriction.

Quillay (Quillaja saponaria Molina) and peumo (Cryptocarya alba [Molina] Looser) are two tree species endemic to Chile that grow in Mediterranean climate zones, characterized by a summer season with high temperatures, high solar radiation, and low soil water availability. A study was conducted with 2-year-old Q. saponaria and C. alba plants and two substrate water conditions: well-watered and controlled water restriction. At the end of the study, anatomical leaf modifications were analyzed. The tissues were anatomically described in transverse sections of juvenile and adult leaves, measuring leaf thickness, cuticle thickness, and cell density of the mesophyll parenchymal tissues. In the young leaves of Q. saponaria plants undergoing water restriction treatment, an increase in cuticle and leaf thickness and a decrease in the density of the palisade and spongy parenchyma were observed. In contrast, a significant reduction in leaf thickness was observed in adult leaves of both species with water restriction treatment. The anatomical changes in the leaves of Q. saponaria and C. alba suggest an adaptation to adverse environmental conditions, such as water restriction.

Factors affecting mammogram breast cancer surveillance effectiveness in the ipsilateral and contralateral breast

AimMammography is the mainstay of imaging surveillance after breast cancer (BC) treatment, but false negatives can occur. The objective of the study was to determine the factors that can predict poorer second breast cancer (SBC) mammogram detection of the ipsilateral and contralateral breast separately. MethodsA multicentre retrospective review was performed on female patients with a previous history of treated BC who developed a second breast cancer (SBC) in the ipsilateral (ISBC) or contralateral breast (CSBC) within 10 years from the first BC. SBC cases that occurred between January 2006 and October 2017 were included from the institutional database. The ISBC and CSBC mammogram-occult (MO) rates were correlated with mammographic breast density as well as various clinical, radiological and histological characteristics of the first BC. Results274 cases of SBC were evaluated. 39.4 % (108/274) of cases were ISBC and 60.6 % (166/274) were CSBC. 35 (32.4 %) of the ISBCs and 42 (25.3 %) of the CSBCs were MO (p = 0.218). On multivariate analysis, symptomatic first BC (p = 0.041), prevailing dense breast tissue at the time of SBC diagnosis (p = 0.003) and trabecular thickening on surveillance mammograms (p = 0.017) were associated with MO ISBC. MO first BC (p < 0.001) was the only factor found to correlate with MO CSBC. ConclusionThe study found various clinical, radiological and pathological factors associated with mammogram surveillance failure for the ipsilateral and contralateral breast. This information can provide additional guidance in the planning of a personalised surveillance program using adjunct imaging screening.

Lower estimates of myocardial perfusion are associated with greater aortic perivascular adipose tissue density in humans independent of aortic stiffness.

Aortic perivascular adipose tissue (aPVAT) density is associated with age-related aortic stiffness in humans and therefore, may contribute to cardiovascular dysfunction. A lower subendocardial viability ratio (SEVR), an estimate of myocardial perfusion, indicates greater cardiovascular disease (CVD) risk and is associated with aortic stiffness in clinical populations. However, the influence of aortic stiffness on the relation between aPVAT density and SEVR/cardiovascular (CV) hemodynamics in apparently healthy adults is unknown. We hypothesize that greater aPVAT density will be associated with lower SEVR and higher CV hemodynamics independent of aortic stiffness. Fourteen (6 males/8 females; mean age, 55.4 ± 5.6 yr; body mass index, 25.5 ± 0.6 kg/m2) adults completed resting measures of myocardial perfusion (SEVR), CV hemodynamics (pulse wave analysis), aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)], and a computed tomography scan to acquire aPVAT and visceral adipose tissue (VAT) density. Greater aPVAT density (i.e., higher density) was associated with lower SEVR (r = -0.78, P < 0.001) and a higher systolic pressure time integral (r = 0.49, P = 0.03), forward pulse height (r = 0.49, P = 0.03), reflected pulse height (r = 0.55, P = 0.02), ejection duration (r = 0.56, P = 0.02), and augmentation pressure (r = 0.69, P = 0.003), but not with the diastolic pressure time integral (r = -0.22, P = 0.22). VAT density was not associated with SEVR or any CV hemodynamic endpoints (all, P > 0.05). Furthermore, the relation between aPVAT density and SEVR remained after adjusting for aortic stiffness (r = -0.66, P = 0.01) but not age (r = -0.24, P > 0.05). These data provide initial evidence for aPVAT as a novel yet understudied local fat depot contributing to lower myocardial perfusion in apparently healthy adults with aging.NEW & NOTEWORTHY Aortic perivascular adipose tissue (aPVAT) density is associated with aging and aortic stiffness in humans and, therefore, may contribute to lower myocardial perfusion. We demonstrate that greater aPVAT, but not visceral adipose tissue density is associated with lower myocardial perfusion and augmentation pressure independent of aortic stiffness, but not independent of age. These data provide novel evidence for aPVAT as a potential therapeutic target to improve myocardial perfusion and cardiovascular function in humans with aging.

Computational insights into tumor invasion dynamics: A finite element approach

The finite element scheme is proposed and analyzed for the solution of an acid-mediated tumor invasion model. The reaction–diffusion equation shows the evolution in the tumor cell density, H+ ions concentration, and healthy tissue density over time. The coupled non-linear partial differential equations are discretized in time with the implicit Euler method and in space with standard Galerkin finite element. To solve the non-linear and coupled terms of the system a fixed point iteration scheme is presented. Moreover, a mass-lumped scheme is adopted to reduce the computation cost. The cut-off method is used to compute the bounded solutions of the PDEs. Finally, The effects of proliferation rate and healthy tissue degradation rate are investigated.