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Targeted and efficient gene delivery systems hold tremendous potential for the improvement of cancer therapy by enabling appropriate modification of biological processes. Herein, we report the design and synthesis of a novel cationic di-block copolypeptide, incorporating homoarginine (HAG) and shikimoyl (LSA) functionalities (HDA-b-PHAGm-b-PLSAn), tailored for enhanced gene transfection specifically in cancer cells. The di-block copolypeptide was synthesized via sequential N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques and its physicochemical properties were characterized, including molecular weight, dispersity, secondary conformation, size, morphology, and surface charge. In contrast to the cationic poly-L-homoarginine, we observed a significantly reduced cytotoxic effect of this di-block copolypeptide due to the inclusion of the shikimoyl glyco-polypeptide block, which also added selectivity in internalizing particular cells. This di-block copolypeptide was internalized via mannose-receptor-mediated endocytosis, which was investigated by competitive receptor blocking with mannan. We evaluated the transfection efficiency of the copolypeptide in HEK 293T (noncancerous cells), MDA-MB-231 (breast cancer cells), and RAW 264.7 (dendritic cells) and compared it with commonly employed transfection agents (Lipofectamine). Our findings demonstrate that the homoarginine and shikimoyl-functionalized cationic di-block copolypeptide exhibits potent gene transfection capabilities with minimal cytotoxic effects, particularly in cancer cells, while it is ineffective for normal cells, indicative of its potential as a promising platform for cancer cell-specific gene delivery systems. To evaluate this, we delivered an artificially designed miRNA-plasmid against Hsp90 (amiR-Hsp90) which upon successful transfection depleted the Hsp90 (a chaperone protein responsible for tumour growth) level specifically in cancerous cells and enforced apoptosis. This innovative approach offers a new avenue for the development of targeted therapeutics with an improved efficacy and safety profile in cancer treatment.
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Hemophagocytic lymphohistiocytosis syndrome (HLH) is a rare hyperinflammatory disorder linked to acute pancreatitis. While there are only a few case reports available on this particular association, we would like to share the case of a 60-year-old man who experienced acute-onset abdominal pain typical of pancreatitis. Three days after admission, he developed fever, pancytopenia, hypertriglyceridemia, and hyperferritinemia. A bone marrow biopsy performed for evaluation of fever revealed hemophagocytosis. Initiation of treatment for HLH showed dramatic improvement. It is important to note that while HLH may be rarely associated with pancreatitis, early diagnosis and treatment is critical and can be life-saving.
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Extrahepatic portal vein thrombosis (EHPVO) is an uncommon cause of portal hypertension. In the long term, patients may develop portal cavernoma cholangiopathy (PCC). Up to 30%-40% of patients with EHPVO may not have shuntable veins and are often difficult to manage surgically. Interventional treatment including portal vein recanalisation-trans jugular intrahepatic portosystemic shunt (PVRecan-TIPS) has been used for patients with EHPVO. However, PV reconstruction-trans jugular intrahepatic portosystemic shunt (PVRecon-TIPS) and portal vein stenting are novel techniques for managing such patients with EHPVO with non-shuntable venous anatomy. In contrast to PVRecan-TIPS, PV reconstruction-TIPS (PVRecon-TIPS) is performed through intrahepatic collaterals. Here we present six cases of PCC who presented with recurrent acute variceal bleeding (AVB) and or refractory biliary stricture. They did not have any shuntable veins. PVRecon-TIPS was performed for five patients whilst PV stenting was done in one. Amongst the six patients, one died of sepsis whilst one who developed hyponatremia and hepatic encephalopathy was salvaged with conservative management. Following the procedure, they were started on anti-coagulation. Decompression of cavernoma was documented in all other patients. Biliary changes improved completely in 40% of patients.
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The absence of any organ of the facial region causes an asymmetrical appearance. This asymmetrical appearance can cause social dilemmas for the patient. The maxillofacial technician, the prosthodontist, and the patient must work closely together to fabricate an epithesis. On the implants, a superstructure is first constructed. Most of it is made up of rings and a bar that joins the implants. The firm acrylic resin base of the epithesis is equipped with clips that serve as the epithesis's retention mechanism. The actual epithesis is made of silicone rubber. The epithesis has to be shaped and colored with extreme caution. An appropriate substitute is an auricular prosthesis that is implant-retained. Microtia, deformity, malformation, and loss of the external ear, either partially or completely, can result from a variety of inherited genetic conditions. To evaluate the symmetry of both ears, artificial intelligence (AI) software is used. An Instagram lens Gridset by crystalwavesxx was used to correct and verify the bilateral symmetry of the patient. This case report primarily focuses on the fabrication of implant-supported auricular prostheses using AI.
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BACKGROUND: Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke. METHODS: In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression. RESULTS: Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs). And after separating the patients based on sex, compared to females, male post-stroke OSA patients with severe WMHs have increased circulating levels of inflammatory chemokine CXCL10 and cytokine Interleukin-10 (IL-10) and significantly decreased levels of Angiopoietin-1 (Ang-1) an important protein responsible for endothelial/vascular integrity functions. Importantly, in a subset of newly diagnosed OSA patients (without prior history of stroke), significantly increased plasma CXCL10 levels and decreased plasma Ang-1 levels were also readily observed when compared to healthy controls, indicating possible altered endothelial integrity and ongoing vascular inflammation in these newly diagnosed OSA patients. CONCLUSIONS: In summary, our study has identified a novel set of plasma biomarkers including PDGF-AA, CXCL10 and Ang-1 for their potential prognostic value for disease outcomes pre- and post-stroke in OSA patients and use as surrogate markers to measure efficacy of treatment modalities.
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Biomarcadores , Apnea Obstructiva del Sueño , Accidente Cerebrovascular , Humanos , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones , Masculino , Biomarcadores/sangre , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/etiología , Anciano , Factor de Crecimiento Derivado de Plaquetas/análisis , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas de Neurofilamentos/sangre , Factor de Necrosis Tumoral alfa/sangre , Quimiocina CXCL10/sangre , Angiopoyetina 1/sangre , Inflamación/sangre , Interleucina-10/sangreRESUMEN
Hematite is an attractive material used as electron transport layer in perovskite-based solar cells. Being hydrophilic in nature it attracts moisture, which can be damaging for perovskite layers. Therefore, it is important to make hematite moisture repelling, which can be beneficial for applications in solar cells or for protecting iron surfaces from further rust formation. In this work, we demonstrate that the systematic irradiation of nanostructured hematite with low-energy argon ions (Ar+) at various ion fluences can change the surface wettability as well as promote the formation of junctions between nanorods. The nano-welded network of the irradiated hematite turns out to be hydrophobic. Using TRI3DYN simulations, ion-induced surface roughening, the presence of surface oxygen vacancies, and joining between adjacent nanorods are predicted. Furthermore, the water-repelling behavior of the irradiated nano-network is evaluated using density functional theory (DFT) simulations by determining the interaction of water molecules with the surface. The interconnected hematite nano-network also shows a notable improvement in electrical conductivity.
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Finding a suitable material for hydrogen storage under ambient atmospheric conditions is challenging for material scientists and chemists. In this work, using a first principles based cluster expansion approach, the hydrogen storage capacity of the Ti2AC (A = Al, Ti, Cr, Mn, Fe, Co, Ni, Cu, and Zn) MAX phase and its alloys was studied. We found that hydrogen is energetically stable in Ti-A layers in which the tetrahedral site consisting of one A atom and three Ti atoms is energetically more favorable for hydrogen adsorption than other sites in the Ti-A layer. Ti2CuC has the highest hydrogen adsorption energy than other Ti2AC phases. We find that the 83.33% Cu doped Ti2AlxCu1-xC alloy structure is both energetically and dynamically stable and can store 3.66 wt% hydrogen under ambient atmospheric conditions, which is higher than that stored by both Ti2AlC and Ti2CuC phases. These findings indicate that the hydrogen capacity of the MAX phase can be significantly improved by doping an appropriate atom species.
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Solar chimney power plant (SCPP) is one of the promising technologies to convert solar energy into carbon-free power generation. It has cost competitiveness, environment friendly and longer service life. Although remarkable advancements were achieved, commercialization aspect of the SCPP has not been established so far. Feasibility assessment of the large-scale plants was carried out by researchers in different climatic conditions across the globe but none of the studies materialized to date. However, it is almost four decades from the development of the first prototype, and no studies have been discussed the barriers to commercialization of the SCPP yet. Therefore, in this present study, a-state-of-the-art review has been presented which discussed the overview of SCPP technologies, factors affecting the flow and performance characteristics of the plant and major barriers in the commercialization aspect of the plant. The overview of SCPP technology including its global status and recent advances are spotlighted. The power potential and carbon emission mitigation of the SCPP based on the climatic condition and geographical location was studied by taking India as an example. In addition to that, the major challenges and opportunities in the SCPP are also addressed. Based on the analysis, a few recommendations are given for commercialization the plant.
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Energía Solar , India , Centrales EléctricasRESUMEN
Hypoxia-induced endothelial cell (EC) dysfunction has been implicated as potential initiators of different pathogenesis, including Alzheimer's disease and vascular dementia. However, in-depth structural, mechanical, and molecular mechanisms leading to EC dysfunction and pathology need to be revealed. Here, we show that ECs exposed to hypoxic conditions readily enter a senescence phenotype. As expected, hypoxia upregulated the expression of vascular endothelial growth factor (VEGFs) and its receptors (VEGFRs) in the ECs. Interestingly, Knockdown of VEGFR-1 expression prior to hypoxia exposure prevented EC senescence, suggesting an important role of VEGFR-1 expression in the induction of EC senescence. Using atomic force microscopy, we showed that senescent ECs had a flattened cell morphology, decreased membrane ruffling, and increased membrane stiffness, demonstrating unique morphological and nanomechanical signatures. Furthermore, we show that hypoxia inhibited the Hippo pathway Yes-associated protein (YAP-1) expression and knockdown of YAP-1 induced senescence in the ECs, supporting a key role of YAP-1 expression in the induction of EC senescence. And importantly, VEGFR-1 Knockdown in the ECs modulated YAP-1 expression, suggesting a novel VEGFR-1-YAP-1 axis in the induction of hypoxia-mediated EC senescence. In conclusion, VEGFR-1 is overexpressed in ECs undergoing hypoxia-mediated senescence, and the knockdown of VEGFR-1 restores cellular structural and nanomechanical integrity by recovering YAP-1 expression.
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Spin-valley coupling in monolayer transition-metal dichalcogenides gives rise to valley polarization and coherence effect, limited by intervalley scattering caused by exciton-phonon, exciton-impurity, and electron-hole exchange interactions (EHEIs). We explore an approach to tune the EHEI by controlling the exciton center of mass momentum (COM) utilizing the photon distribution of higher-order optical vortex beams. By virtue of this, we have observed exciton-COM-dependent valley depolarization and decoherence, which gives us the ability to probe the valley relaxation time scale in a steady-state measurement. Our steady-state technique to probe the valley dynamics can open up a new paradigm to explore the physics of excitons in two-dimensional systems.
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Converting a nonwetting surface to a highly wetting one, aided by ultraviolet radiation, is well explored. Here, in this work, we show just the reverse behavior of a copper-copper oxide nanocomposite surface where ultraviolet radiation turned the superhydrophilic surface to a superhydrophobic one. This observation is explained both experimentally and theoretically using first-principles density functional theory-based calculations considering the metal-oxygen (Cu-O) bond breaking and related change in surface chemistry. This observation has further been corroborated with electron irradiation on the same nanocomposite material. To the best of our knowledge, for the first time, we show that the radiation-induced breaking of the copper-oxygen bond makes the nanostructure surface energetically unfavorable for water adsorption.
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Algae are one of the most viable feedstock options that can be converted into different bioenergies viz., bioethanol, biobutanol, biodiesel, biomethane, biohydrogen, etc. owing to their renewable, sustainable and economic credibility features. Algal biomass to fuel biorefining process is generally classified into three categories as chemical, biochemical and thermochemical methods. The present article aims to provide a state-of-the-art review on the factors affecting the thermochemical conversion process of algal biomass to bioenergy. Further, reaction conditions of each techniques (torrefaction, pyrolysis, gasification and hydrothermal process) influence biochar, bio-oil and syngas yield were discussed. Reaction parameters or factors such as reactor temperature, residence time, pressure, biomass load/feedstock composition, catalyst addition and carrier gas flow affecting process efficiency in terms of product yield and quality were spotlighted and extensively discussed with copious literature. It also presents the novel insights on production of solid (char), liquid (bio-oil) and gaseous (syngas) biofuel through torrefaction, pyrolysis and gasification, respectively. It is found that the energy intensive drying was more efficient mode involved in thermochemical process for wet algal biomass. However other modes of thermochemical process were having unique feature on improving the product yield and quality. Among the various factors, reaction temperature and residence time were relatively more important factors which affected the process efficiency. The other factors signposted in this review will lay a roadmap to researchers to choose an optimal thermochemical conditions for high quality end product. Lastly, the perspectives and challenges in thermochemical conversion algae biomass to biofuels were also discussed.
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Biocombustibles , Gases , Biomasa , Plantas , TemperaturaRESUMEN
Thermochemical techniques are being operated for the complete conversion of diverse biomasses to biofuels. Among the feedstocks used for thermochemical processes, algae are the promising biomass sources owing to their advantages over other feedstocks such as biomass productivity, renewability and sustainability. Due to several advantages, algal biomass is considered as a source for third generation biofuel. This review work aims to provide a state-of-the-art on the most commonly used thermochemical methods namely torrefaction, pyrolysis, and gasification processes. Furthermore, the production of biofuels from algal biomass was comprehensively articulated. Different algal strains used in thermochemical techniques and their conditions of operation were compared and discussed. The yield and quality of solid (char), liquid (bio-oil) and gaseous (syngas) products obtained through thermochemical methods were reviewed and analysed to understand the efficacy of each technique. End product percentage, quality and advantages of the torrefaction, pyrolysis, and gasification were summarized. It is found that the biofuel produced from the torrefaction process was easy to store and deliver and had higher utilization efficiency. Among the existing thermochemical methods, the pyrolysis process was widely used for the complete conversion of algal biomass to bio-oil or char. This study also revealed that the gasification (supercritical) method was the most energy efficient process for conversion of wet algal biomass. The reactor used in the thermochemical process and its subprocess was also highlighted. This study revealed that the fixed bed reactor was suitable for small scale production whereas the fluidized bed reactor could be scaled up for industrial production. In addition to that environmental impacts of the products were also spotlighted. Finally, the perspectives and challenges of algal biomass to bioenergy conversion were addressed.
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Biocombustibles , Gases , BiomasaRESUMEN
Polymer blend made from poly(ε - caprolactone)/chitosan (PCL/CHT) offers interesting opportunities for biological applications. The paper presents a new way to fabricate PCL/CHT double-porosity (macrovoids with interconnected microporosity) membrane materials from a chemical optimization of the solvent and non-solvent phases and from a modified phase inversion technique. By varying the PCL/CHT proportion, it is shown that it is possible to improve the chemical and physical properties of the CHT carbohydrate polymer. The PCL/CHT membranes are fully characterized in term of physico-chemical properties (ATR-FTIR, XRD and DSC) to understand the miscibility of the two-polymer blend. Morphological characterization by SEM shows that by increasing CHT wt% in the blend, the size of the macrovoids was increasing. Rapid enzymatic degradation of PCL from all the blend was found by using lipase (from P. cepacia). The mechanisms at the origin of the morphological structuration of the material is also discussed. To test the ability to operate these materials as small diameter vascular scaffolds, cell culture with human umbilical vein endothelial cells (HUVECs) were carried out on the membrane and the results analyzed with laser scanning confocal microscopy (LSCM). Data suggest that the blend membrane with higher concentration of CHT polymer wt% have suitable properties that promote high number of cells on the surface by maintaining cellular cytoskeleton integrity within 3 days. The blend membrane with a double porous morphology could be potentially applicable in future for small diameter vascular graft application. The surface macrovoids (20-90⯵m) could be useful for three-dimensional cellular adhesion and proliferation and interconnected microporous spongy network (7-20⯵m) is expected to transfer essential nutrients, oxygen, growth factor between the macrovoids and the supernatant.
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Quitosano/química , Poliésteres/química , Ingeniería de Tejidos , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Microscopía Confocal , Porosidad , Propiedades de Superficie , ViscosidadRESUMEN
In this paper, we developed membrane scaffolds to mimic the biochemical and biophysical properties of human mesenchymal stem cell (hMSC) niches to help direct self-renewal and proliferation providing to cells all necessary chemical, mechanical and topographical cues. The strategy was to create three-dimensional membrane scaffolds with double porosity, able to promote the mass transfer of nutrients and to entrap cells. We developed poly (Æ-caprolactone) (PCL)/chitosan (CHT) blend membranes consisting of double porous morphology: (i) surface macrovoids (big pores) which could be easily accessible for hMSCs invasion and proliferation; (ii) interconnected microporous network to transfer essential nutrients, oxygen, growth factors between the macrovoids and throughout the scaffolds. We varied the mean macrovoid size, effective surface area and surface morphology by varying the PCL/CHT blend composition (100/0, 90/10, 80/20, 70/30). Membranes exhibited macrovoids connected with each other through a microporous network; macrovoids size increased by increasing the CHT wt%. Cells adhered on the surfaces of PCL/CHT 100/0 and PCL/CHT 90/10 membranes, that are characterized by a high effective surface area and small macrovoids while PCL/CHT 80/20 and PCL/CHT 70/30 membranes with large macrovoids and low effective surface area entrapped cells inside macrovoids. The scaffolds were able to create a permissive environment for hMSC adhesion and invasion promoting viability and metabolism, which are important for the maintenance of cell integrity. We found a relationship between hMSCs proliferation and oxygen uptake rate with surface mean macrovoid size and effective surface area. The macrovoids enabled the cell invasion into the membrane and the microporosity ensured an adequate diffusive mass transfer of nutrients and metabolites, which are essential for the long-term maintenance of cell viability and functions.
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Caproatos/química , Quitosano/química , Lactonas/química , Células Madre Mesenquimatosas/fisiología , Polímeros/química , Nicho de Células Madre , Andamios del Tejido/química , Materiales Biocompatibles/química , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Células Cultivadas , Humanos , Ensayo de Materiales/métodos , Células Madre Mesenquimatosas/citología , Porosidad , Ingeniería de Tejidos/métodosRESUMEN
Senescent cells accumulate in various peripheral tissues during aging and have been shown to exacerbate age-related inflammatory responses. We recently showed that exposure to neurotoxic amyloid ß (Aß1-42) oligomers can readily induce a senescence phenotype in human brain microvascular endothelial cells (HBMECs). In the present work, we used atomic force microscopy (AFM) to further characterize the morphological properties such as cell membrane roughness and cell height and nanomechanical properties such as Young's modulus of the membrane (membrane stiffness) and adhesion resulting from the interaction between AFM tip and cell membrane in Aß1-42 oligomer-induced senescent human brain microvascular endothelial cells. Morphological imaging studies showed a flatter and spread-out nucleus in the senescent HBMECs, both characteristic features of a senescent phenotype. Furthermore, the mean cell body roughness and mean cell height were lower in senescent HBMECs compared to untreated normal HBMECs. We also observed increased stiffness and alterations in the adhesion properties in Aß1-42 oligomer-induced senescent endothelial cells compared to the untreated normal HBMECs suggesting dynamic reorganization of cell membrane. We then show that vascular endothelial growth factor receptor 1 (VEGFR-1) knockdown or overexpression of Rho GTPase Rac 1 in the endothelial cells inhibited senescence and reversed these nanomechanical alterations, confirming a direct role of these pathways in the senescent brain endothelial cells. These results illustrate that nanoindentation and topographic analysis of live senescent brain endothelial cells can provide insights into cerebrovascular dysfunction in neurodegenerative diseases such as Alzheimer's disease.
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Péptidos beta-Amiloides/metabolismo , Senescencia Celular/fisiología , Células Endoteliales/metabolismo , Enfermedad de Alzheimer/metabolismo , Fenómenos Biomecánicos/fisiología , Encéfalo/metabolismo , Técnicas de Cultivo de Célula , Membrana Celular/metabolismo , Endotelio Vascular/metabolismo , Humanos , Microscopía de Fuerza Atómica/métodos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
In this work we report for the first time a method to modify the surface of Cu2O nanowires in a controllable way and physically weld them into a network form, which contributes to higher electrical conductivity as well as a strong water-repelling nature. We have used state-of-the-art theoretical calculations to support our experimental observations. We demonstrate how varying the irradiation fluence can modulate the surface and decorate the nanowire with a uniform distribution of Cu8O nanocrystals due to preferential sputtering. While several well studied joining techniques are available for carbon and metal-based nanowires, the same information for ceramic nanowires is scarce at present. The current study sheds light into this and a state-of-the-art 3D simulation technique predicts most of the modifications including surface modulation, oxygen depletion and welding. The welded network shows higher electrical conductivity than the unwelded assembly. With Cu2O being of p-type the current ion beam joining technique shows a novel path for fabricating p-i-n junctions or solar cell devices through bottom-up approach. Furthermore, we have explored the response of this network to moisture. Our calculation based on density functional theory predicts the hydrophilic nature of individual copper oxide nanowires both before and after irradiation. However, the network shows a strong water-repelling nature, which has been explained quantitatively using the Cassie-Baxter model.
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BACKGROUND: Identifying disease activity in Takayasu arteritis (TAK) is challenging. This study aimed to investigate the value of quantitative characterization with computed tomography angiography in the assessment of disease activity in patients with TAK. METHODS: We retrospectively analysed the data on 162 aortic CT angiography from 140 TAK patients. Patients were categorized based on disease activity according to the National Institutes of Health criteria into two groups: active disease group (nâ¯=â¯65) and inactive disease group (nâ¯=â¯97). RESULTS: Patients with active TAK had a thicker wall compared with patients with inactive TAK (5.2⯱â¯2.4â¯mm vs. 2.5⯱â¯0.8â¯mm, pâ¯<â¯0.001). The relative post-contrast enhancement ratio of the thickened wall was higher in active TAK than in inactive TAK (1.5⯱â¯0.3 vs. 1.1⯱â¯0.2, pâ¯<â¯0.001). Given a thickness cutoff of 3.3â¯mm, sensitivity for active-phase TAK was 83.1%, specificity 89.7%, positive predictive value 84.4%, and negative predictive value 88.8%. With a relative post-contrast enhancement ratio cutoff of 1.2, sensitivity for active-phase TAK was 89.2%, specificity 76.3%, positive predictive value 71.6%, and negative predictive value 91.3%. In receiver-operating characteristic curves comparison, maximal wall thickness and relative post-contrast enhancement ratio were superior to C-reactive protein and erythrocyte sedimentation rate for determining active phase disease (pâ¯<â¯0.05). CONCLUSIONS: Quantitative characterization with CT angiography was a useful tool to assess disease activity in TAK patients. Maximal wall thickness and relative post-contrast enhancement ratio have a high sensitivity and specificity for detecting TAK activity.
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Aorta Torácica/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Arteritis de Takayasu/diagnóstico , Remodelación Vascular , Adulto , Aorta Torácica/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Arteritis de Takayasu/fisiopatología , Adulto JovenRESUMEN
Tissue engineering is an interdisciplinary field, wherein scientists from different backgrounds collaborate to address the challenge of replacing damaged tissues and organs through the in vitro fabrication of functional and transplantable biological structures. Because the development and optimization of tissue engineering strategies rely on the complex interaction of cells, materials, and the physical-chemical tissue microenvironment, there is a need for experimental models that allow controlled studies of these aspects. Organs-on-chips (OOCs) have recently emerged as in vitro models that capture the complexity of human tissues in a controlled manner, while including functional readouts related to human organ physiology. OOCs consist of multiple microfluidic cell culture compartments, which are interfaced by porous membranes or hydrogels in which human cells can be cultured, thereby providing a controlled culture environment that resembles the microenvironment of a certain organ, including mechanical, biochemical, and geometrical aspects. Because OOCs provide both a well-controlled microenvironment and functional readouts, they provide a unique opportunity to incorporate, evaluate, and optimize materials for tissue engineering. In this study, we introduce a polymeric blend membrane with a three-dimensional double-porous morphology prepared from a poly(É-caprolactone)-chitosan blends (PCL-CHT) by a modified liquid-induced phase inversion technique. The membranes have different physicochemical, microstructural, and morphological properties depending on different PCL-CHT ratios. Big surface pores (macrovoids) provide a suitable microenvironment for the incorporation of cells or growth factors, whereas an interconnected small porous (macroporous) network allows transfer of essential nutrients, diffusion of oxygen, and removal of waste. Human umbilical vein endothelial cells were seeded on the blend membranes embedded inside an OOC device. The cellular hydraulic resistance was evaluated by perfusing culture medium at a realistic transendothelial pressure of 20 cmH2O or 2 kPa at 37°C after 1 and 3 days postseeding. By introducing and increasing CHT weight percentage, the resistance of the cellular barrier after 3 days was significantly improved. The high tuneability over the membrane physicochemical and architectural characteristics might potentially allow studies of cell-matrix interaction, cell transportation, and barrier function for optimization of vascular scaffolds using OOCs. Impact Statement Organs-on-chips (OOCs) offer interesting potential for progress in the treatment of diseases and injury in the growing field of tissue engineering and regenerative medicine. The article presents a new way to develop polymer membrane with a tunable microstructured morphology and to implement this biomaterial inside an OOC device. The reader should find measurements of the transendothelial hydraulic resistance in real time during endothelial cells culture: a simple and controlled way of mimicking human physiological condition for vascular tissue regeneration. This combination of novel biomaterial inside an OOC will explore innovative ideas in tissue engineering field.
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Endotelio/fisiología , Dispositivos Laboratorio en un Chip , Membranas Artificiales , Endotelio/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Polímeros/farmacología , Porosidad , PresiónRESUMEN
This study aims to investigate the image quality and radiation dose of prospective ECG-triggered 128-slice dual-source CT (DSCT) angiography in the delineation of coronary arteries in infants with congenital heart disease (CHD). Sixty-three infants with CHD were randomly assigned into two groups: prospective ECG-triggered sequential protocol (group 1) and high-pitch spiral protocol (group 2). Patients were selected to the protocols randomly. A five-point scoring system was applied to study the capability of detecting coronary arteries. A score of < 3 represents non-diagnostic. Effective radiation dose (ED) was calculated. The visualized rate for original, proximal, middle and distal segments of the coronary arteries was 98%, 95%, 94% and 83%, respectively in group 1, 93%, 82%, 53% and 34%, respectively in group 2. There were no significant demographic differences in the identification rate between the two groups as to the original and most of the proximal segments. Significant demographic differences were found in middle and distal segments (p < 0.05). The mean ED of the high pitch group and the sequential group was 0.33 ± 0.11 mSv and 0.63 ± 0.16 mSv, respectively. Both the prospective ECG-gated high-pitch mode and the sequential mode for 128-slice DSCT allow satisfactory delineation of original and most of the proximal segments of coronary arteries in infants with CHD. However, an ECG-gated sequential mode is recommended when detailed anatomic assessment of the whole coronary arteries are needed since the ECG-gated high-pitch mode is limited in the delineation of middle and distal segments of the coronary arteries.