Vascular Properties Research Articles

A little on the nose: A mosquito targets the nostrils of tree frogs for a blood meal

AbstractAs the females of most mosquitoes require a blood meal to provision their eggs, they can be a vector of parasites and pathogens that have profound impacts on both animal and human populations. Understanding the interactions between mosquitoes and their hosts, including animal and feeding site preferences, could thus provide valuable insights into disease transmission. In this study, we present a highly specific feeding strategy observed in a mosquito from Australia (Mimomyia elegans). Over 3 years of fieldwork, we found this mosquito feeding exclusively on the nostrils when using several amphibian species as hosts. Mosquitoes were observed initially landing on the backs of hosts before walking towards the nostrils, potentially minimizing detection and mitigating the risk of predation or defensive responses. This remarkable level of feeding site specificity suggests strong selection pressures that are causing the nostril to be the optimal location for blood extraction on amphibians. Possible explanations include the presence of thinner, more accessible skin tissue or enhanced vascular properties in the nostril region. Understanding mosquito host preferences, points of contact and feeding site specificity could provide valuable insights into disease transmission among amphibians, as mosquitoes have been identified as potential vectors of pathogens like the amphibian chytrid fungus.

Therapeutic modulation of epigenetic readers rescues obesity-induced vascular dysfunction: role of endothelium and perivascular adipose tissue

Abstract Background/Introduction Bromodomain and extraterminal proteins (BET), particularly BRD4, are epigenetic readers modulating transcriptional programs implicated in inflammation, cancer and renal disease. Therapeutic potential of BRD4 modulation in cardiometabolic disorders remains elusive. Purpose We investigate BRD4-related transcriptional programs and therapeutic modulation in mouse and human models of cardiometabolic disease. Methods Small arteries (100-300 μM) from healthy subjects (n=13) and patients with obesity (n=13) were dissected from visceral fat biopsies collected during elective laparoscopy and mounted on a pressurised myograph to assess the ex-vivo effects of BRD4 inhibition on vascular function. Vasorelaxation to acetylcholine and acetylcholine+L-NAME were evaluated at baseline and after incubation with the BRD4 inhibitor RVX-208. Anti-IL-1β, anti-IL-6 receptor and anti-TNF-α were also employed to assess the relative contribution of distinct BRD4-related pathways. Vasorelaxation was performed in the presence or in the absence of perivascular adipose tissue (PVAT). An experimental mouse model of cardiometabolic disease (high-fat diet+L-NAME supplementation) was orally administered RVX-208 (150 mg/kg) or vehicle for 10 days (n=6 each group) to test in vivo effect of chronic BRD4 inhibition on endothelial and PVAT functions. Vascular and PVAT levels of cytosolic and mitochondrial ROS and nitric oxide were assessed by confocal microscopy; protein and gene expression was measured by Western blot and qPCR. Transcriptional changes upon BRD4 inhibition were investigated by a custom PCR array. Results In patients with obesity, endothelial-dependent vasorelaxation and vascular nitric oxide availability were impaired. ROS levels, as well as TNF-α, IL-1β and IL-6, were increased in the vessel wall and PVAT. In these subjects, RVX-208 substantially attenuated ex-vivo vascular dysfunction. The effect was more pronounced in vessels with intact PVAT, suggesting a restoration of the PVAT anti-contractile phenotype (Figure 1). Distinct ex-vivo modulation of well-established inflammatory pathways showed that the effect observed with BRD4 inhibition was stronger than with anti-IL-1β, anti-IL-6 receptor and anti-TNF-α. In vivo, chronic treatment with RVX-208 restored endothelial vasorelaxation by rescuing PVAT dysfunction. Gene expression profiling in PVAT from cardiometabolic mice unveiled hexokinase-2 (HK2) - a glycolytic enzyme implicated in mitochondrial dysfunction and inflammation - as the top downregulated gene by RVX-208 treatment (Figure 2). Conclusions Therapeutic modulation of BRD4 restores cardiometabolic-related vascular dysfunction and PVAT anti-contractile properties. These effects are explained by a suppression of PVAT inflammation (IL-1β, IL-6 and TNF-α), likely driven by HK2 activation. BET inhibitors might represent promising epi-drugs for the prevention and treatment of vascular dysfunction, a hallmark of cardiometabolic disease.

Bioprinted dermis with human adipose tissue-derived microvascular fragments promotes wound healing.

Tissue-engineered skin is an effective material for treating large skin defects in a clinical setting. However, its use is limited owing to vascular complications. Human adipose tissue-derived microvascular fragments (HaMVFs)are vascularized units that form vascular networks by rapid reassembly. In this study, we designed a vascularized bionic skin tissue using a three-dimensional (3D) bioprinter of HaMVFs and human fibroblasts encapsulated in a hybrid hydrogel composed of GelMA, HAMA, and fibrinogen. Tissues incorporating HaMVFs showed good in vitro vascularization and mechanical properties after UV crosslinking and thrombin exposure. Thus, the tissue could be sutured appropriately to the wound. In vivo, the vascularized 3D bioprinted skin promoted epidermal regeneration, collagen maturation in the dermal tissue, and vascularization of the skin tissue to accelerate wound healing. Overall, vascularized 3D bioprinted skin with HaMVFs is an effective material for treating skin defects and may be clinically applicable to reduce the necrosis rate of skin grafts.

Myocardial, Valvular, and Vascular Structural and Functional Properties in Acromegaly.

Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during adulthood. Acromegaly could cause a typical cardiomyopathy characterized by left ventricular hypertrophy associated with diastolic dysfunction, which later could progress to systolic dysfunction. Moreover, some valvular and vascular abnormalities are also associated with acromegaly. This present review aims to summarize available information regarding acromegaly-associated abnormalities in myocardial, valvular, and vascular structural and functional properties and their relationship to disease activity and treatment options.

Musculoskeletal ultrasound: a technical and historical perspective.

During the past four decades, musculoskeletal ultrasound has become popular as an imaging modality due to its low cost, accessibility, and lack of ionizing radiation. The development of ultrasound technology was possible in large part due to concomitant advances in both solid-state electronics and signal processing. The invention of the transistor and digital computer in the late 1940s was integral in its development. Moore's prediction that the number of microprocessors on a chip would grow exponentially, resulting in progressive miniaturization in chip design and therefore increased computational power, added to these capabilities. The development of musculoskeletal ultrasound has paralleled technical advances in diagnostic ultrasound. The appearance of a large variety of transducer capabilities and rapid image processing along with the ability to assess vascularity and tissue properties has expanded and continues to expand the role of musculoskeletal ultrasound. It should also be noted that these developments have in large part been due to a number of individuals who had the insight to see the potential applications of this developing technology to a host of relevant clinical musculoskeletal problems. Exquisite high-resolution images of both deep and small superficial musculoskeletal anatomy, assessment of vascularity on a capillary level and tissue mechanical properties can be obtained. Ultrasound has also been recognized as the method of choice to perform a large variety of interventional procedures. A brief review of these technical developments, the timeline over which these improvements occurred, and the impact on musculoskeletal ultrasound is presented below.

Endothelial Cell Dysfunction and Hypoxia as Potential Mediators of Pain in Fabry Disease: A Human-Murine Translational Approach.

Fabry disease (FD) is caused by α-galactosidase A (AGAL) enzyme deficiency, leading to globotriaosylceramide accumulation (Gb3) in several cell types. Pain is one of the pathophysiologically incompletely understood symptoms in FD patients. Previous data suggest an involvement of hypoxia and mitochondriopathy in FD pain development at dorsal root ganglion (DRG) level. Using immunofluorescence and quantitative real-time polymerase chain reaction (qRT PCR), we investigated patient-derived endothelial cells (EC) and DRG tissue of the GLA knockout (KO) mouse model of FD. We address the question of whether hypoxia and mitochondriopathy contribute to FD pain pathophysiology. In EC of FD patients (P1 with pain and, P2 without pain), we found dysregulated protein expression of hypoxia-inducible factors (HIF) 1a and HIF2 compared to the control EC (p < 0.01). The protein expression of the HIF downstream target vascular endothelial growth factor A (VEGFA, p < 0.01) was reduced and tube formation was hampered in the P1 EC compared to the healthy EC (p < 0.05). Tube formation ability was rescued by applying transforming growth factor beta (TGFβ) inhibitor SB-431542. Additionally, we found dysregulated mitochondrial fusion/fission characteristics in the P1 and P2 EC (p < 0.01) and depolarized mitochondrial membrane potential in P2 compared to control EC (p < 0.05). Complementary to human data, we found upregulated hypoxia-associated genes in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). At protein level, nuclear HIF1a was higher in the DRG neurons of old GLA KO mice compared to WT mice (p < 0.01). Further, the HIF1a downstream target CA9 was upregulated in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). Similar to human EC, we found a reduction in the vascular characteristics in GLA KO DRG compared to WT (p < 0.05). We demonstrate increased hypoxia, impaired vascular properties, and mitochondrial dysfunction in human FD EC and complementarily at the GLA KO mouse DRG level. Our data support the hypothesis that hypoxia and mitochondriopathy in FD EC and GLA KO DRG may contribute to FD pain development.

Anatomy of the complete mouse eye vasculature explored by light-sheet fluorescence microscopy exposes subvascular-specific remodeling in development and pathology

Eye development and function rely on precise establishment, regression and maintenance of its many sub-vasculatures. These crucial vascular properties have been extensively investigated in eye development and disease utilizing genetic and experimental mouse models. However, due to technical limitations, individual studies have often restricted their focus to one specific sub-vasculature. Here, we apply a workflow that allows for visualization of complete vasculatures of mouse eyes of various developmental stages. Through tissue depigmentation, immunostaining, clearing and light-sheet fluorescence microscopy (LSFM) entire vasculatures of the retina, vitreous (hyaloids) and uvea were simultaneously imaged at high resolution. In silico dissection provided detailed information on their 3D architecture and interconnections. By this method we describe successive remodeling of the postnatal iris vasculature, involving sprouting and pruning, following its disconnection from the embryonic feeding hyaloid vasculature. In addition, we demonstrate examples of conventional and LSFM-mediated analysis of choroidal neovascularization after laser-induced wounding, showing added value of the presented workflow in analysis of modelled eye disease. These advancements in visualization and analysis of the respective eye vasculatures in development and complex eye disease open for novel observations of their functional interplay at a whole-organ level.

Cardiovascular Risk in Childhood is Associated With Carotid Intima-Media Thickness and Stiffness in Adolescents and Young Adults: The KiGGS Cohort

PurposeCardiovascular risk factors are widespread among children and adolescents and may lead to accelerated vascular aging in middle adulthood. However, data are scarce on shorter-term consequences, for example, on associated distinctive vascular properties before age 30 years. This study analyzes the association of childhood exposure to cardiovascular risk factors with carotid properties in adolescents and young adults. MethodsFour thousand thirty one participants from the population-based German Health Interview and Examination Survey for Children and Adolescents cohort (aged 3–17 years) had carotid intima-media thickness (CIMT) and distensibility coefficient (DC) measurements at the second follow-up (aged 14–28 years). The assessment of cardiovascular risk factors at baseline included information about arterial hypertension, obesity, dyslipidemia, and passive smoking. ResultsSingle risk factors and the exposure to multiple cardiovascular risk factors were associated with elevated CIMT and decreased DC. Relative risks for CIMT ≥ 90th centile and/or DC ≤ 10th centile were increased in participants exposed to two (RRCIMT = 1.45 [95% confidence interval 1.11–1.91], p < .05; RRDC = 1.37 [1.02–1.84], p < .05) and ≥ three risk factors (RRCIMT = 1.66 [1.05–2.62], p < .05; RRDC = 1.25 [0.71–2.21], p > .05). DiscussionExposure to multiple cardiovascular risk factors starting in childhood is associated with measurably increased CIMT and carotid stiffness in late adolescence and early adulthood. These findings underline the importance of population-wide preventive measures to promote optimal cardiovascular health.

OR2806 Levosulpiride-Induced Hyperprolactinemia For The Treatment Of Diabetic Macular Edema: A Phase 2 Pilot Clinical Trial

Abstract Disclosure: C. Clapp: None. C.D. Núñez-Amaro: None. M. López: None. E. Adán-Castro: None. M. Robles Osorio: None. R. García-Franco: None. M. García-Roa: None. Y. Villalpando: None. P. Ramírez-Neria: None. N. Pineiro: None. J.F. Rubio-Mijangos: None. J. Sánchez: None. G. Ramirez-Hernandez: None. L. Siqueiros-Márquez: None. N. Díaz-Lezama: None. E. López-Star: None. T. Bertsch: None. G. Martínez de la Escalera: None. J. Triebel: None. Vasoinhibin is a fragment of prolactin that inhibits the permeability and growth of blood vessels. The prokinetic dopamine D2 receptor blocker, levosulpiride, elevates the circulating levels of prolactin and the accumulation of vasoinhibin in the vitreous of patients with proliferative diabetic retinopathy (PDR) (1) suggesting clinical benefits due to the vascular properties of vasoinhibin. Here, we describe the 2-month results of a phase 2 clinical trial (2) investigating the biological activity of levosulpiride in center-involving diabetic macular edema (DME). This prospective, randomized, double-masked, dual-center, placebo-controlled, pilot study was carried out in individuals (aged 40 to 69 years) with DME involving the center of the macula and best-corrected visual acuity (BCVA) between 58 and 16 ETDRS letters at 4 m (20/16 to 20/100 Snellen equivalent) or with PDR undergoing elective pars plana vitrectomy. Oral treatment (TID) with levosulpiride or placebo was for 8 weeks in DME patients or for the 1 week before vitrectomy in PDR patients. Primary outcome measures included changes from baseline in BCVA, central foveal thickness (CFT), and mean macular volume (MMV) every 2 weeks for 8 weeks in placebo- (17 patients, 18 eyes) and levosulpiride- (17 patients, 22 eyes) treated DME groups; whereas vitreous levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were primary outcomes in PDR patients after placebo (18 patients) or levosulpiride (18 patients). Starting at 4 weeks, levosulpiride improved changes from baseline in BCVA (P &amp;lt; 0.037), CFT (P &amp;lt; 0.013), and MMV (P &amp;lt; 0.002) compared to placebo. At 8 weeks, the proportion of eyes gaining &amp;gt;5 letters (41% vs. 28%), loosing &amp;gt; 21 μm in CFT (55% vs. 28%), and dropping &amp;gt; 0.06 mm3 in MMV (65% vs. 29%) were higher in levosulpiride vs placebo. The overall grading of visual (BCVA) and structural parameters (CFT, MMV, OCT macula image, fundoscopy, and fluorescein angiography) showed improvement with levosulpiride (P = 0.029). Levosulpiride reduced VEGF (P = 0.025) and PlGF (P= 0.008) levels in the vitreous of PDR patients. There were no apparent adverse side-effects. In conclusion, oral levosulpiride administration for 8 weeks improved visual and structural outcomes in patients with center involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted. Reference: (1) Núñez-Amaro et al., Transl Vis Sci Technol. 2020 Aug 17;9(9):27. (2) www.clinicaltrials.gov, ID: NCT03161652; Supported by UNAM grant 405PC. Presentation: Sunday, June 18, 2023

Biological Macromolecule Hydrogel Based on Recombinant Type I Collagen/Chitosan Scaffold to Accelerate Full-Thickness Healing of Skin Wounds.

The development of biological macromolecule hydrogel dressings with fatigue resistance, sufficient mechanical strength, and versatility in clinical treatment is critical for accelerating full-thickness healing of skin wounds. Therefore, in this study, multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure were fabricated to accelerate wound healing. The resulting biological macromolecule hydrogel possesses sufficient mechanical strength, fatigue resistance, and healing properties, including antibacterial, antioxygenic, self-healing, vascularization, hemostatic, and adhesive abilities. Chitosan and recombinant type I collagen formed the scaffold network, which was the first covalent crosslinking network of the hydrogel. The second physical crosslinking network comprised the coordination of a metal-polyphenol structure, i.e., Cu2+ with the catechol group of dopamine methacrylamide (DMA) and stacking of DMA benzene rings. Double-crosslinked networks are interspersed and intertwined in the hydrogel to reduce the mechanical strength and increase its fatigue resistance, making it more suitable for clinical applications. Moreover, the biological macromolecule hydrogel can continuously release Cu2+, which provides strong antibacterial and vascularization properties. An in vivo full-thickness skin defect model confirmed that multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure can facilitate the formation of granulation tissue and collagen deposition for a short period to promote wound healing. This study highlights that this biological macromolecule hydrogel is a promising acute wound-healing dressing for biomedical applications.

Preparation of a scaffold for a vascular network channel with spatially varying diameter based on sucrose

In the past few decades, although tissue engineering has made significant progress and achieved many accomplishments, there are still some key problems that remain unsolved. One of the urgent research challenges in this field is how to prepare large-scale tissue engineering scaffolds with spatially complex structures. In this work, a sacrificial template process using sucrose as the sacrificial material and a gelatin/microbial transglutaminase mixed solution as the bio-scaffold material is proposed to fabricate a bio-scaffold with multi-level branching and spatially complex vascular network channels that mimic the structure and function of the human vascular network. To validate the feasibility of the fabrication process and the rationality of the process parameters, the morphological characteristics, connectivity of vascular network channels, shaping accuracy, and mechanical properties of the bio-scaffold were tested and analyzed. The results showed that the bio-scaffold fabricated using this process had a complete morphology and excellent connectivity. The diameter of the sucrose sacrificial template showed a linear relationship with the feeding speed, and the average diameter error rate between the sucrose sacrificial template and the vascular network channels inside the bio-scaffold was less than 8%. The mechanical properties of the bio-scaffold met the requirements for large-scale tissue defect repair. To evaluate the effect of the bio-scaffold on cell activity, human umbilical vein endothelial cells (HUVECs) were seeded into the vascular network channels of the bio-scaffold, and their attachment, growth, and proliferation on the surface of the vascular network channels were observed. To further assess the biocompatibility of the bio-scaffold, the bio-scaffold was implanted subcutaneously in the dorsal tissue of rats, and the tissue regeneration status was compared and analyzed through immunohistochemical analysis. The results showed that the vascular network channels within the bio-scaffold allowed uniform cell attachment, growth, with fewer dead cells and high cell viability. Moreover, clear cell attachment and growth were observed within the vascular network channels of the bio-scaffold after implantation in rats. These results indicate that the fabricated bio-scaffold meets the basic performance requirements for the repair and regeneration of large-scale tissue defects, providing a new approach for oxygen and nutrient transport in large-scale tissues and opening up new avenues for clinical applications.

Effects of Zinc and Strontium Doping on In Vitro Osteogenesis and Angiogenesis of Calcium Silicate/Calcium Phosphate Cement.

Based on multiple biological functions (mainly osteogenesis and angiogenesis) of bioactive ions, Zn/Sr-doped calcium silicate/calcium phosphate cements (Zn/Sr-CS/CPCs, including 10Zn-CS/CPC, 20Sr-CS/CPC, and 10Zn/20Sr-CS/CPC) were prepared by the addition of Zn and Sr dual active ions into CS/CPC to further accelerate its bone regeneration in this study. The physicochemical and biological properties of the Zn/Sr-CS/CPCs were systematically investigated. The results showed that the setting time was slightly prolonged, the compressive strength and porosity did not change much, and all groups maintained good injectability after the doping of Zn and Sr. Besides, the doping of Zn and Sr had little effect on the phase and microstructure of hydrated products of CS/CPC. The degradation rate of Zn/Sr-CS/CPCs decreased after doping with Zn and Sr. In mouse bone marrow mesenchymal stem cells (mBMSC) experiments, all Zn/Sr-CS/CPCs stimulated the viability, adhesion, proliferation, and alkaline phosphatase (ALP) activity together with osteogenesis-related genes (ALP, Runx2, Col-I, OCN, and OPN). The further addition of Zn and Sr played better and synergistic roles in in vitro osteogenesis. Thereinto, 10Zn/20Sr-CS/CPC manifested the optimum in vitro osteogenic performance. As for human umbilical vein endothelial cell (HUVEC) experiments, the incorporation of CS doped with Zn and Sr into CPC possessed good vascularization properties of proliferation, NO secretion, tube formation, and the expression of angiogenesis-related genes (VEGF, bFGF, and eNOS). In conclusion, the doping of Zn and Sr into CS/CPC could exhibit excellent osteogenesis and good angiogenesis potentials and 10Zn/20Sr-CS/CPC could be considered as a promising candidate in bone repair.

Adverse cardiovascular effects of long-term exposure to diethyl phthalate in the rat aorta

Phthalates are classified as priority environmental pollutants, since they are ubiquitous in the environment, have endocrine disrupting properties and can contribute to impaired health. Used primarily in personal care products and excipients for pharmaceuticals, diethyl phthalate (DEP) is a short-chain alkyl phthalate that has been linked to decreased blood pressure, glucose tolerance, and increased gestational weight gain in humans, while in animals it has been associated with atherosclerosis and metabolic syndrome. Although all these findings are related to risk factors or cardiovascular diseases, DEP's vascular impacts still need to be clarified. Thus, performing ex vivo and in vitro experiments, we aimed to understand the vascular DEP effects in rat. To evaluate the vascular contractility of rat aorta exposed to different doses of DEP (0.001–1000 μM), an organs bath was used; and resorting to a cell line of the rat aorta vascular smooth muscle, electrophysiology experiments were performed to analyse the effects of a rapid (within minutes with no genomic effects) and a long-term (24 h with genomic effects) exposure of DEP on the L-type Ca2+ current (ICa,L), and the expression of several genes related with the vascular function. For the first time, vascular electrophysiological properties of an EDC were analysed after a long-term genomic exposure. The results show a hormetic response of DEP, inducing a Ca2+ current inhibition of the rat aorta, which may be responsible for impaired cardiovascular electrical health. Thus, these findings contribute to a greater scientific knowledge about DEP's effects in the cardiovascular system, specifically its implications in the development of electrical disturbances like arrhythmias and its possible mechanisms.

Kinsenoside mitigates myocardial ischemia/reperfusion-induced ferroptosis via activation of the Akt/Nrf2/HO-1 pathway

Ischemia-induced myocardial infarction is regarded as one of the major killers of humans worldwide. Kinsenoside (KD), a primary active ingredient derived from Anoectochilus roxburghii, shows antioxidant and vascular protective properties. Myocardial ischemia/reperfusion (I/R) injury is associated with oxidative damage and could be regulated by KD. However, its targets and the exact mechanism by which it operates remains unclear. The aim of this study was to investigate the role of KD in myocardial I/R injury and to define the mechanism by which it works. We established both myocardial I/R model in vivo and hypoxia/reoxygenation (H/R) cardiomyocyte model in vitro in this study. KD can attenuate I/R-induced myocardial injury in vivo and inhibit H/R-induced injury in vitro in a dose-dependent manner. KD increased mitochondrial membrane potential, SOD activity, and GSH activity in cardiomyocytes, whereas MDA accumulation, iron accumulation, and Mito-ROS production were decreased. We intersected differentially expressed genes (DEGs) from RNA-seq results with ferroptosis-related genes, and found KD significantly downregulated COX2 expression and upregulated GPX4 expression. These findings were further confirmed by Western blot analysis. Additionally, KD increased AKT phosphorylation and Nrf2 translocation into the nucleus, as well as HO-1 expression. When Akt or Nrf2 were inhibited in the KD group, the anti-ferroptosis properties of KD were nullified. Thus, Kinsenoside may exert anti-ferroptosis effect in myocardial I/R injury by decreasing mitochondrial dysfunction and increasing anti-oxidation through the Akt/Nrf2/HO-1 signaling pathway, suggesting it could be used as a potential therapeutic agent for myocardial reperfusion injury.

Psoriasis Vulgaris

Psoriasis is an inflammatory disease of the skin that is chronic, persistent, and repetitive due to complex abnormalities in epidermal growth and differentiation as well as multiple abnormalities of biochemical, immunological, and vascular properties. Generally, lesions in the form of erythematous plaques are layered with a silvery white color with firm borders. Its location can be localized, for example on the elbows, knees or scalp or affect almost 100% of the body area. The prevalence of psoriasis varies from 1 to 12% among different populations worldwide with a male to female ratio of 1:1. The cause of psoriasis until now is still unclear and what is already known are the factors that influence the onset of psoriasis based on epidemiological data, including nation, region, climate, heredity, and other factors.

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity – a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM). We showed that dynamic 2-DG-enhanced MSOT (DGE-MSOT) is powerful in acquiring hemodynamic rate constants, including Ktrans and Kep, via systemically injecting a low dose of 2-DG-800 (0.5 µmol/kg b.w.). In our study, both ETM and RRM are efficient in deriving hemodynamic parameters in the tumor. Area-under-curve (AUC) values (which correlate to metabolism), and Ktrans and Kep values, can effectively distinguish tumor from muscle. Hemodynamic parameters also demonstrated correlations to hemoglobin, oxyhemoglobin, and blood oxygen level (SO2) measurements by spectral unmixing of the MSOT data. Together, our study for the first time demonstrated the capability of DGE-MSOT in assessing vascular hemodynamics of tumors.

Fracture of porcine aorta—Part 2: FEM modelling and inverse parameter identification

The mechanics of vascular tissue, particularly its fracture properties, are crucial in the onset and progression of vascular diseases. Vascular tissue properties are complex, and the identification of fracture mechanical properties relies on robust and efficient numerical tools. In this study, we propose a parameter identification pipeline to extract tissue properties from force-displacement and digital image correlation (DIC) data. The data has been acquired by symconCT testing porcine aorta wall specimens. Vascular tissue is modelled as a non-linear viscoelastic isotropic solid, and an isotropic cohesive zone model describes tissue fracture. The model closely replicated the experimental observations and identified the fracture energies of 1.57±0.82 kJ m−2 and 0.96±0.34 kJ m−2 for rupturing the porcine aortic media along the circumferential and axial directions, respectively. The identified strength was always below 350 kPa, a value significantly lower than identified through classical protocols, such as simple tension, and sheds new light on the resilience of the aorta. Further refinements to the model, such as considering rate effects in the fracture process zone and tissue anisotropy, could have improved the simulation results. Statement of significanceThis paper identified porcine aorta’s biomechanical properties using data acquired through a previously developed experimental protocol, the symmetry-constraint compact tension test. An implicit finite element method model mimicked the test, and a two-step approach identified the material’s elastic and fracture properties directly from force-displacement curves and digital image correlation-based strain measurements. Our findings show a lower strength of the abdominal aorta as compared to the literature, which may have significant implications for the clinical evaluation of the risk of aortic rupture.

Radiomics characterization of tissues in an animal brain tumor model imaged using dynamic contrast enhanced (DCE) MRI

Here, we investigate radiomics-based characterization of tumor vascular and microenvironmental properties in an orthotopic rat brain tumor model measured using dynamic-contrast-enhanced (DCE) MRI. Thirty-two immune compromised-RNU rats implanted with human U-251N cancer cells were imaged using DCE-MRI (7Tesla, Dual-Gradient-Echo). The aim was to perform pharmacokinetic analysis using a nested model (NM) selection technique to classify brain regions according to vasculature properties considered as the source of truth. A two-dimensional convolutional-based radiomics analysis was performed on the raw-DCE-MRI of the rat brains to generate dynamic radiomics maps. The raw-DCE-MRI and respective radiomics maps were used to build 28 unsupervised Kohonen self-organizing-maps (K-SOMs). A Silhouette-Coefficient (SC), k-fold Nested-Cross-Validation (k-fold-NCV), and feature engineering analyses were performed on the K-SOMs’ feature spaces to quantify the distinction power of radiomics features compared to raw-DCE-MRI for classification of different Nested Models. Results showed that eight radiomics features outperformed respective raw-DCE-MRI in prediction of the three nested models. The average percent difference in SCs between radiomics features and raw-DCE-MRI was: 29.875% ± 12.922%, p < 0.001. This work establishes an important first step toward spatiotemporal characterization of brain regions using radiomics signatures, which is fundamental toward staging of tumors and evaluation of tumor response to different treatments.

Creating a context for recipient vessel selection in deep inferior epigastric perforator flap breast reconstruction

In autologous tissue breast reconstruction, recipient vessels are important for artery perfusion and venous drainage to ensure free flap survival. There are insufficient clinical outcomes to select efficient recipient vessels in bi-pedicled deep inferior epigastric perforator (DIEP) flap reconstruction. We presented a retrospective observational series of 108 patients regarding the diameter, anastomosis time, and re-anastomosis rate in internal mammary (IM), circumflex scapular (CS), thoracodorsal (TD), thoracoacromial (TA), lateral thoracic (LT), and internal mammary perforator (IMP) vessels of bi-pedicled DIEP flaps for breast reconstruction after mastectomy. The outcomes were the vessel re-anastomosis rate, flap failure rate, vessel anastomosis time, and complications. Data were gleaned from the chi-square test, Fisher's test, and analysis of variance using Scheffe's test as a post hoc analysis. The level of significance was p<0.05. There were no significant differences in the diameters of the artery, first vein, and second vein across the recipient vessels (p>0.05). However, the anastomosis time was longer in IM and TA than in CS, TD, and LT (p<0.001). Also, there were no significant differences for re-anastomosis, flap necrosis, and fat necrosis among different recipient vessels (p>0.05). Because of the altered mastectomy incisions, this study provides complete anatomical vascular properties and suggests that altering recipient vessel selection for bi-pedicled DIEP flaps can shorten anastomosis time and better conceal scars.

Understanding recovery of language after stroke: insights from neurovascular MRI studies.

Stroke causes a disruption in blood flow to the brain that can lead to profound language impairments. Understanding the mechanisms of language recovery after stroke is crucial for the prognosis and effective rehabilitation of people with aphasia. While the role of injured brain structures and disruptions in functional connectivity have been extensively explored, the relationship between neurovascular measures and language recovery in both early and later stages has not received sufficient attention in the field. Fully functioning healthy brain tissue requires oxygen and nutrients to be delivered promptly via its blood supply. Persistent decreases in blood flow after a stroke to the remaining non-lesioned tissue have been shown to contribute to poor language recovery. The goal of the current paper is to critically examine stroke studies looking at the relationship between different neurovascular measures and language deficits and mechanisms of language recovery via changes in neurovascular metrics. Measures of perfusion or cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide complementary approaches to understanding neurovascular mechanisms post stroke by capturing both cerebral metabolic demands and mechanical vascular properties. While CBF measures indicate the amount of blood delivered to a certain region and serve as a proxy for metabolic demands of that area, CVR indices reflect the ability of the vasculature to recruit blood flow in response to a shortage of oxygen, such as when one is holding their breath. Increases in CBF during recovery beyond the site of the lesion have been shown to promote language gains. Similarly, CVR changes, when collateral vessels are recruited to help reorganize the flow of blood in hypoperfused regions, have been related to functional recovery post stroke. In the current review, we highlight the main findings in the literature investigating neurovascular changes in stroke recovery with a particular emphasis on how language abilities can be affected by changes in CBF and CVR. We conclude by summarizing existing methodological challenges and knowledge gaps that need to be addressed in future work in this area, outlining a promising avenue of research.