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AIM: The transition from paediatric to adult care for patients with inflammatory bowel disease (IBD) is associated with an increased risk of treatment non-adherence, hospitalizations and emergency department (ED) use. We established a new young adult IBD clinic (YAC) in Melbourne to capture this at-risk population. We aimed to assess patient satisfaction as well as clinical outcomes. METHODS: All patients who attended the YAC between its inception in November 2016 and November 2018 were recruited to our YAC group, 61 patients in total. A control group was selected from the pre-existing adult clinic (AC) at our service, 34 patients in total. IBD-related ED (IBD-ED) visits were collected for all patients. We compared IBD-ED visits in the 2 years before and after attending the clinic for the first time. Patient satisfaction was assessed using the IBD-Patient Satisfaction Questionnaire. RESULTS: There was an overall decrease in IBD-ED visits between the pre-clinic and post-clinic periods in both the YAC (42.9% reduction) and AC (69.2% reduction) (P < 0.001). Patient satisfaction was high amongst both services with YAC patients indicating higher satisfaction with communication (P = 0.015). CONCLUSION: There was a reduction in IBD-ED visits in both the YAC and the AC, high patient satisfaction, and statistically higher satisfaction with communication in the YAC. We speculate the importance of a YAC is to capture those patients in the peri-transitional period at risk of being lost to follow-up or not previously referred for specialist care.
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Enfermedades Inflamatorias del Intestino , Transición a la Atención de Adultos , Niño , Enfermedad Crónica , Servicio de Urgencia en Hospital , Hospitalización , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Satisfacción del Paciente , Adulto JovenRESUMEN
All-solid-state batteries (ASSBs) based on ceramic materials are considered a key technology for automobiles and energy storage systems owing to their high safety and stability. However, contact issues between the electrode and solid-electrolyte materials and undesired chemical reaction occurring at interfaces have hindered their development. Herein, the chemical compatibility and structural stability of composite mixtures of the layered cathode materials Li1- x Ni0.5 Co0.2 Mn0.3 O2 (NCM523) with the garnet-type solid electrolyte Li6.25 Ga0.25 La3 Zr2 O12 (LLZO-Ga) during high-temperature co-sintering under various gas flowing conditions are investigated. In situ high-temperature X-ray diffraction analysis of the composite materials reveals that Li diffusion from LLZO-Ga to NCM523 occurs at high temperature under synthetic air atmosphere, resulting in the decomposition of LLZO-Ga into La2 Zr2 O7 and the recovery of charged NCM523 to the as-prepared state. The structural stability of the composite mixture at high temperature is further investigated under N2 atmosphere, revealing that Li diffuses toward the opposite direction and involves the phase transition of LLZO-Ga from a cubic to tetragonal structure and the reduction of the NCM523 cathode to Ni metal. These findings provide insight into the structural stability of layered cathode and garnet-type solid-electrolyte composite materials and the design of stable interfaces between them via co-sintering for ASSBs.
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Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, p < 0.05), visceral adipose tissue mass (-46%, p < 0.05), and visceral adipocyte size (-20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, p < 0.05) and infiltration of macrophages (-72%, p < 0.05), while concomitantly upregulating the expression of fatty acid ß-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice.
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Dislipidemias/prevención & control , Hígado Graso/prevención & control , Fenofibrato/uso terapéutico , Hipolipemiantes/uso terapéutico , Obesidad Abdominal/prevención & control , Adipocitos/efectos de los fármacos , Animales , Dieta Alta en Grasa , Evaluación Preclínica de Medicamentos , Femenino , Fenofibrato/farmacología , Hipolipemiantes/farmacología , Grasa Intraabdominal/metabolismo , Ratones Endogámicos C57BL , Ovariectomía , PPAR gamma/metabolismoRESUMEN
Our previous studies demonstrated that peroxisome proliferator-activated receptor α (PPARα) activation reduces weight gain and improves insulin sensitivity in obese mice. Since excess lipid accumulation in non-adipose tissues is suggested to be responsible for the development of insulin resistance, this study was undertaken to examine whether the lemon balm extract ALS-L1023 regulates hepatic lipid accumulation, obesity, and insulin resistance and to determine whether its mechanism of action involves PPARα. Administration of ALS-L1023 to high-fat-diet-induced obese mice caused reductions in body weight gain, visceral fat mass, and visceral adipocyte size without changes of food consumption profiles. ALS-L1023 improved hyperglycemia, hyperinsulinemia, glucose and insulin tolerance, and normalized insulin-positive ß-cell area in obese mice. ALS-L1023 decreased hepatic lipid accumulation and concomitantly increased the expression of PPARα target genes responsible for fatty acid ß-oxidation in livers. In accordance with the in vivo data, ALS-L1023 reduced lipid accumulation and stimulated PPARα reporter gene expression in HepG2 cells. These effects of ALS-L1023 were comparable to those of the PPARα ligand fenofibrate, while the PPARα antagonist GW6471 inhibited the actions of ALS-L1023 on lipid accumulation and PPARα luciferase activity in HepG2 cells. Higher phosphorylated protein kinase B (pAkt)/Akt ratios and lower expression of gluconeogenesis genes were observed in the livers of ALS-L1023-treated mice. These results indicate that ALS-L1023 may inhibit obesity and improve insulin sensitivity in part through inhibition of hepatic lipid accumulation via hepatic PPARα activation.
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Resistencia a la Insulina/genética , Hígado/metabolismo , Obesidad/tratamiento farmacológico , PPAR alfa/genética , Extractos Vegetales/administración & dosificación , Adipocitos/citología , Adipocitos/efectos de los fármacos , Animales , Tamaño de la Célula/efectos de los fármacos , Dieta Alta en Grasa , Células Hep G2 , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL , Obesidad/inducido químicamente , Obesidad/genética , Obesidad/metabolismo , PPAR alfa/metabolismo , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
An in vitro model for ischemia/reperfusion injury has not been well-established. We hypothesized that this failure may be caused by serum deprivation, the use of glutamine-containing media, and absence of acidosis. Cell viability of H9c2 cells was significantly decreased by serum deprivation. In this condition, reperfusion damage was not observed even after simulating severe ischemia. However, when cells were cultured under 10% dialyzed FBS, cell viability was less affected compared to cells cultured under serum deprivation and reperfusion damage was observed after hypoxia for 24 h. Reperfusion damage after glucose or glutamine deprivation under hypoxia was not significantly different from that after hypoxia only. However, with both glucose and glutamine deprivation, reperfusion damage was significantly increased. After hypoxia with lactic acidosis, reperfusion damage was comparable with that after hypoxia with glucose and glutamine deprivation. Although high-passage H9c2 cells were more resistant to reperfusion damage than low-passage cells, reperfusion damage was observed especially after hypoxia and acidosis with glucose and glutamine deprivation. Cell death induced by reperfusion after hypoxia with acidosis was not prevented by apoptosis, autophagy, or necroptosis inhibitors, but significantly decreased by ferrostatin-1, a ferroptosis inhibitor, and deferoxamine, an iron chelator. These data suggested that in our SIR model, cell death due to reperfusion injury is likely to occur via ferroptosis, which is related with ischemia/reperfusion-induced cell death in vivo. In conclusion, we established an optimal reperfusion injury model, in which ferroptotic cell death occurred by hypoxia and acidosis with or without glucose/glutamine deprivation under 10% dialyzed FBS.
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Three-dimensional (3D) core-shell structured graphene-silver nanowire (AgNW) hybrid fillers are prepared through facile spray drying and an optical welding process. The spray drying process enables formation of a core-shell structure with AgNWs attached onto the spherical graphene surface by van der Waals force and surface tension during evaporation. AgNW shell is optically welded for enhanced mechanical stability and interfacial resistance reduction. 3D core-shell structured graphene-AgNW hybrid fillers are partially embedded into polydimethylsiloxane (PDMS) to fabricate highly stretchable and conductive nanocomposites. The electrical conductivity of nanocomposites largely increases up to â¼116 S cm-1 and the electrical properties are well maintained under high stretchability of â¼140% strain with 100 stretching cycles despite small amount of AgNW. These enhancements are attributed to the formation of electrically conducting network by excellent dispersion property of spherical graphene core in PDMS matrix and low contact resistance of AgNW shell. We anticipate that 3D core-shell structured graphene-AgNW/PDMS nanocomposites have great potential for application in various stretchable electronic devices.
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Developing a thermally stable nanofluid that can maintain good thermo-conductive and flow performance at moderate or elevated temperatures for prolonged periods of time is a great challenge in heat transfer applications. Here, the thermal conductivity and rheological properties as well as their thermal stability characteristics of a nanofluid containing two-dimensional (2D) hexagonal boron nitride nanosheets (h-BNNSs) in ethylene glycol (EG) are presented, in comparison with those for a graphene oxide (GO) nanofluid as a counterpart. In place of a surfactant, hydroxyl functional groups covalently bound to the BNNS surface provided excellent compatibility and stable dispersion of the particles within EG at temperatures up to 90 °C. Owing to the percolation effect of the 2D sheets, the thermal conductivity of the EG base fluid was significantly enhanced by 80% at 5 vol% of BNNS, superior to that of the GO fluid. Moreover, the BNNS fluids exhibited excellent long-term stability at 90 °C for 5 d without loss of their high thermal conductivity, low viscosity and electrical insulating property, whereas the GO fluids underwent thermal degradation with irreversible particle aggregation and increasing viscosity due to the selective chemical reduction of the surface functional groups (i.e., C-O groups) of the GO.
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In this paper, we propose a specific algorithm based on the least-square method to predict the incidence angle insensitivity of a metamaterial absorber. The proposed algorithm was analyzed on a metamaterial absorber design with circular sectors on the top layer and a full copper cover on the bottom layer. We retrieved the parameters of inductance, capacitance, and conductance from the equivalent circuit of the metamaterial absorber at different incidence angles of 0°, 30°, 65°, and 70° under both transverse electric and transverse magnetic polarization. The complex impedances calculated from the optimal parameter retrieval are compared with the complex impedances from full-wave simulation at each incidence angle. The calculated and simulated results show excellent agreement, and the proposed algorithm can be used to design angle-insensitive metamaterial absorbers.
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The melanocortin receptors (MCRs) are members of the G protein-coupled receptor (GPCR) 1 superfamily with seven transmembrane (TM) domains. Among them, the melanocortin-4 receptor (MC4R) subtype has been highlighted recently by genetic studies in obese humans. In particular, in a patient with severe early-onset obesity, a novel heterozygous mutation in the MC4R gene was found in an exchange of Asp to Asn in the 90th amino acid residue located in the TM 2 domain (MC4RD90N). Mutations in the MC4R gene are the most frequent monogenic causes of severe obesity and are described as heterozygous with loss of function. We determine solution structures of the TM 2 domain of MC4R (MC4RTM2) and compared secondary structure of Asp90 mutant (MC4RTM2-D90N) in a micelle environment by nuclear magnetic resonance (NMR) spectroscopy. NMR structure shows that MC4RTM2 forms a long α-helix with a kink at Gly98. Interestingly, the structure of MC4RTM2-D90N is similar to that of MC4RTM2 based on data from CD and NMR spectrum. However, the thermal stability and homogeneity of MC4RD90N is quite different from those of MC4R. The structure from molecular modeling suggests that Asp90(2.50) plays a key role in allosteric sodium ion binding. Our data suggest that the sodium ion interaction of Asp90(2.50) in the allosteric pocket of MC4R is essential to its function, explaining the loss of function of the MC4RD90N mutant.
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Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Receptor de Melanocortina Tipo 4/química , Receptor de Melanocortina Tipo 4/metabolismo , Dodecil Sulfato de Sodio/química , Secuencia de Aminoácidos , Sitios de Unión , Dicroismo Circular , Humanos , Iones , Espectroscopía de Resonancia Magnética , Micelas , Modelos Moleculares , Datos de Secuencia Molecular , Estabilidad Proteica , Estructura Secundaria de Proteína , Receptor de Melanocortina Tipo 4/aislamiento & purificación , Sales (Química)/farmacología , Sodio/metabolismo , Soluciones , Homología Estructural de ProteínaRESUMEN
This novel vertically and horizontally symmetric slotted-sector design aims to realize an angle- and polarization-insensitive metamaterial absorber. The unit-cell symmetries achieve polarization insensitivity, while an optimized slotted-sector inner angle enables angle insensitivity. Because the absorptivity of a metamaterial absorber depends on the incident angle and polarization, many researchers have studied angle- and polarization-insensitive unit cells. In this work, a novel vertically and horizontally symmetric slotted sector is proposed in order to realize an angle- and polarization-insensitive metamaterial absorber. The absorber performance is demonstrated with full-wave simulation and measurements. Angular sensitivity is studied for different slotted-sector inner angles. For an 85° inner angle, the simulated absorptivity exceeds 90% and the frequency variation is less than 1.2% up to 70° incidence. The measured absorptivity at 10.34 GHz is close to 98.5% for all polarization angles at normal incidence. As the incidence angle varies from 0° to 70°, the measured absorptivity at 10.34 GHz remains above 90% in the transverse electric mode.
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A frequency-tunable metamaterial absorber is designed with the unit cell consisting of a varactor-loaded fishnet-like resonator. This geometry allows all cathode and anode pads of the unit cells to be connected to their counterparts. Hence, only the ends of the periodic structure need to be biased, reducing the complexity of the bias network. The absorber was modeled using a full-wave simulation tool and verified experimentally with a 20×20 unit-cell prototype. Using free-space measurements, the absorber shows >90% absorption ratio from 3.96 to 5.29 GHz with a frequency tuning ratio of 28.7%, when the reverse voltage varied from 0 to 19 V.
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A stretchable metamaterial absorber is proposed in this study. The stretchability was achieved by liquid metal and polydimethylsiloxane (PDMS). To inject liquid metal, microfluidic channels were fabricated using PDMS powers and microfluidic-channel frames, which were built using a three-dimensional printer. A top conductive pattern and ground plane were designed after considering the easy injection of liquid metal. The proposed metamaterial absorber comprises three layers of PDMS substrate. The top layer is for the top conductive pattern, and the bottom layer is for the meandered ground plane. Flat PDMS layers were inserted between the top and bottom PDMS layers. The measured absorptivity of the fabricated absorber was 97.8% at 18.5 GHz, and the absorption frequency increased from 18.5 to 18.65 GHz as the absorber was stretched from its original length (5.2 cm) to 6.4 cm.
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In this paper, a novel flexible tunable metasurface absorber is proposed for large-scale remote ethanol sensor applications. The proposed metasurface absorber consists of periodic split-ring-cross resonators (SRCRs) and microfluidic channels. The SRCR patterns are inkjet-printed on paper using silver nanoparticle inks. The microfluidic channels are laser-etched on polydimethylsiloxane (PDMS) material. The proposed absorber can detect changes in the effective permittivity for different liquids. Therefore, the absorber can be used for a remote chemical sensor by detecting changes in the resonant frequencies. The performance of the proposed absorber is demonstrated with full-wave simulation and measurement results. The experimental results show the resonant frequency increases from 8.9 GHz to 10.04 GHz when the concentration of ethanol is changed from 0% to 100%. In addition, the proposed absorber shows linear frequency shift from 20% to 80% of the different concentrations of ethanol.
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The scalable preparation of two-dimensional hexagonal boron nitride (h-BN) is essential for practical applications. Despite intense research in this area, high-yield production of two-dimensional h-BN with large-size and high solubility remains a key challenge. In the present work, we propose a scalable exfoliation process for hydroxyl-functionalized BN nanoplatelets (OH-BNNPs) by a simple ball milling of BN powders in the presence of sodium hydroxide via the synergetic effect of chemical peeling and mechanical shear forces. The hydroxide-assisted ball milling process results in relatively large flakes with an average size of 1.5 µm with little damage to the in-plane structure of the OH-BNNP and high yields of 18%. The resultant OH-BNNP samples can be redispersed in various solvents and form stable dispersions that can be used for multiple purposes. The incorporation of the BNNPs into the polyethylene matrix effectively enhanced the barrier properties of the polyethylene due to increased tortuosity of the diffusion path of the gas molecules. Hydroxide-assisted ball milling process can thus provide simple and efficient approaches to scalable preparation of large-size and highly soluble BNNPs. Moreover, this exfoliation process is not only easily scalable but also applicable to other layered materials.
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Graphene flakes (GFs) with minimized defects and oxidation ratios are incorporated into polyethylene (PE) to enhance the moisture barrier. GFs produced involving solvothermal intercalation show extremely low oxidation rates (3.17%), and are noncovalently functionalized in situ, inducing strong hydrophobicity. The fabricated composite possesses the best moisture barrier performance reported for a polymer-graphene composite.
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The scalable preparation of graphene in control of its structure would significantly improve its commercial viability. Despite intense research in this area, the size control of defect-free graphene (df-G) without any trace of oxidation or structural damage remains a key challenge. Here, we propose a new scalable route for generating df-G with a controllable size of submicron to micron through sequential insertion of potassium and pyridine at low temperature. Structural and chemical analyses confirm that the df-G perfectly preserves the intrinsic properties of graphene. The Co3O4 (<50 nm) wrapped by â¼ 10.5 µm(2) df-G has unprecedented capacity, rate capability, and cycling stability with capacities as high as 1050 mAh g(-1) at 500 mA g(-1) and 900 mAh g(-1) at 1000 mA g(-1) even after 200 cycles, which suggests enticing potential for the use in high performance lithium ion batteries.
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The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for B. cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B12). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B12) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.
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Antibacterianos , Burkholderia cenocepacia , Mutación , Especies Reactivas de Oxígeno , Tobramicina , Vitamina B 12 , Vitamina B 12/farmacología , Vitamina B 12/metabolismo , Antibacterianos/farmacología , Burkholderia cenocepacia/efectos de los fármacos , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/metabolismo , Tobramicina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Acilcoenzima A/metabolismo , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética , Ciclo del Ácido Cítrico/efectos de los fármacos , Humanos , Metilmalonil-CoA Mutasa/genética , Metilmalonil-CoA Mutasa/metabolismo , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/tratamiento farmacológico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
Developing a non-noble metal-based bifunctional electrocatalyst with high efficiency and stability for overall water splitting is desirable for renewable energy systems. We developed a novel method to fabricate a heterostructured electrocatalyst, comprising a NiCoP nanoneedle array grown on Ti3C2Tx MXene-coated Ni foam (NCP-MX/NF) using a dip-coating hydrothermal method, followed by phosphorization. Due to the abundance of active sites, enhanced electronic kinetics, and sufficient electrolyte accessibility resulting from the synergistic effects of NCP and MXene, NCP-MX/NF bifunctional alkaline catalysts afford superb electrocatalytic performance, with a low overpotential (72 mV at 10 mA cm-2 for HER and 303 mV at 50 mA cm-2 for OER), a low Tafel slope (49.2 mV dec-1 for HER and 69.5 mV dec-1 for OER), and long-term stability. Moreover, the overall water splitting performance of NCP-MX/NF, which requires potentials as low as 1.54 and 1.76 V at a current density of 10 and 50 mA cm-2, respectively, exceeded the performance of the Pt/Câ¥IrO2 couple in terms of overall water splitting. Density functional theory (DFT) calculations for the NCP/Ti3C2O2 interface model predicted the catalytic contribution to interfacial formation by analyzing the electronic redistribution at the interface. This contribution was also evaluated by calculating the adsorption energetics of the descriptor molecules (H2O and the H and OER intermediates).
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ß-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble ß-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived ß-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.
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The influence of surface modifications on the mechanical properties of epoxy-hexagonal boron nitride nanoflake (BNNF) nanocomposites is investigated. Homogeneous distributions of boron nitride nanoflakes in a polymer matrix, preserving intrinsic material properties of boron nitride nanoflakes, is the key to successful composite applications. Here, a method is suggested to obtain noncovalently functionalized BNNFs with 1-pyrenebutyric acid (PBA) molecules and to synthesize epoxy-BNNF nanocomposites with enhanced mechanical properties. The incorporation of noncovalently functionalized BNNFs into epoxy resin yields an elastic modulus of 3.34 GPa, and 71.9 MPa ultimate tensile strength at 0.3 wt%. The toughening enhancement is as high as 107% compared to the value of neat epoxy. The creep strain and the creep compliance of the noncovalently functionalized BNNF nanocomposite is significantly less than the neat epoxy and the nonfunctionalized BNNF nanocomposite. Noncovalent functionalization of BNNFs is effective to increase mechanical properties by strong affinity between the fillers and the matrix.