RESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infections in infants worldwide, significantly affecting their health and contributing to the global healthcare burden. We aimed to examine healthcare resource utilisation patterns and costs for infants under one year old with confirmed RSV infection across subgroups of different gestational ages and health conditions and the cost implications of RSV infections over time, thereby demonstrating the economic burden of the disease. METHODS: This retrospective cohort study utilised nationwide claims data from the Korea Health Insurance Review and Assessment Service for infants under one year of age with confirmed RSV infection in the first year of life from January 2017 to April 2022. The infants were stratified into three subgroups based on their gestational age and health status: unhealthy preterm, healthy preterm, and full-term infants. A descriptive analysis was conducted to estimate healthcare utilization by type of resource and costs related to the treatment of RSV. RESULTS: Out of 93,585 RSV infections identified, 31,206 patients met the inclusion criteria; these included 963 unhealthy preterm, 1,768 healthy preterm and 28,475 full-term infants. In our study, 76.3% of the infants with confirmed RSV infection required intensive care, including hospitalisation and more critical interventions such as intensive care unit (ICU) or mechanical ventilation (MV). The total average cost of RSV management was notably higher for unhealthy preterm infants ($ 6,325; 95% confidence interval (CI): $ 5,484-7,165) than for healthy preterm ($ 1,134; 95% CI: $ 1,006 - 1,261) and full-term infants ($ 606; 95% CI: 583-630). Our findings confirmed a significant epidemiological and economic burden, with infants at greater risk-shorter gestational age and poorer health conditions. Furthermore, we observed a marked increase in the total average cost of RSV management during COVID-19, reflecting the complex interplay between RSV and pandemic-related healthcare dynamics. CONCLUSION: Our findings provide evidence for the significant economic burden of RSV infection among infants, with considerable disparities based on gestational age and health status subgroups. However, RSV prevention policies should also recognise that healthy preterm or full-term infants who receive intensive care face a significant disease burden.
Asunto(s)
Costos de la Atención en Salud , Aceptación de la Atención de Salud , Infecciones por Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/economía , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/terapia , Lactante , Femenino , Estudios Retrospectivos , Masculino , Recién Nacido , República de Corea/epidemiología , Costos de la Atención en Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Recien Nacido Prematuro , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Edad Gestacional , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Estudios de Cohortes , Virus Sincitial Respiratorio HumanoRESUMEN
Introduction: Weight-loss strategies through meal replacements are effective and sustainable options. However, few studies have assessed their effects on weight loss including body composition through protein-supplemented meal replacements targeting the Asian population, including Koreans. This study aimed to assess the effectiveness and safety of a protein-supplemented very-low-calorie diet (PSVLCD) for weight reduction and changes in body composition in individuals with obesity over a 12-month long-term period. Methods: In total, 106 participants with obesity were randomly assigned to a PSVLCD or control group (food-based calorie-restricted diet). Body weight, waist circumference, body composition, and blood marker levels were measured throughout the study. Statistical analyses were performed to compare outcomes between the groups. Results: Among the 106 participants, 84 completed the 12-month follow-up. Intention-to-treat analysis showed that the mean weight loss from baseline to 12 months was -6.86 kg (8.21% of baseline weight) in the PSVLCD group and - 4.66 kg (5.47% of initial body weight) in the control group; the difference was -2.20 kg with a marginally significant interval (95% confidence interval [CI], -4.90; 0.50). Waist circumference (-8.35 cm vs. -4.85 cm; mean difference, -3.49 cm; 95% CI, -6.48 to -0.50) and visceral fat area (-28.28 cm2 vs. -13.26 cm2; mean difference, -15.03cm2; 95% CI, -29.01 to -1.04) also significantly decreased in the PSVLCD group at 12 months. Discussion: The PSVLCD group demonstrated a substantial initial reduction in waist circumference that was sustained over the study period, alongside a marginally significant decrease in weight. These findings suggest that a protein-supplemented very-low-calorie diet may be an effective strategy for long-term weight management and body composition improvement in individuals with obesity. Clinical trial registration: ClinicalTrials.gov, identififer NCT04597788.
RESUMEN
Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)/silent information regulator 1 (Sirt-1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) mitochondrial biogenesis pathway and the Akt/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Diferenciación Celular , Dexametasona , Fibras Musculares Esqueléticas , Atrofia Muscular , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Sirtuina 1 , Serina-Treonina Quinasas TOR , Animales , Dexametasona/farmacología , Atrofia Muscular/inducido químicamente , Atrofia Muscular/prevención & control , Atrofia Muscular/metabolismo , Transducción de Señal/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Serina-Treonina Quinasas TOR/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Diferenciación Celular/efectos de los fármacos , Sirtuina 1/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Extractos Vegetales/farmacología , Masculino , Proteolisis/efectos de los fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Línea Celular , Proteínas Ligasas SKP Cullina F-box/metabolismo , Proteínas Ligasas SKP Cullina F-box/genética , Ratones Endogámicos C57BL , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas de Motivos TripartitosRESUMEN
Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals.
Asunto(s)
Encéfalo , Animales , Ratones , Encéfalo/metabolismo , Encéfalo/fisiología , Neuronas/metabolismo , Canales Iónicos/metabolismo , Canales Iónicos/genética , Optogenética/métodos , Estimulación Encefálica Profunda/métodos , Estimulación Encefálica Profunda/instrumentación , Masculino , Ratones Endogámicos C57BLRESUMEN
Resistin plays an important role in the pathophysiology of obesity-mediated insulin resistance in mice. However, the biology of resistin in humans is quite different from that in rodents. Therefore, the association between resistin and insulin resistance remains unclear in humans. Here, we tested whether and how the endocannabinoid system (ECS) control circulating peripheral blood mononuclear cells (PBMCs) that produce resistin and infiltrate into the adipose tissue, heart, skeletal muscle, and liver, resulting in inflammation and insulin resistance. Using human PBMCs, we investigate whether the ECS is connected to human resistin. To test whether the ECS regulates inflammation and insulin resistance in vivo, we used 2 animal models such as "humanized" nonobese diabetic/Shi-severe combined immunodeficient interleukin-2Rγ (null) (NOG) mice and "humanized" resistin mouse models, which mimic human body. In human atheromatous plaques, cannabinoid 1 receptor (CB1R)-positive macrophage was colocalized with the resistin expression. In addition, resistin was exclusively expressed in the sorted CB1R-positive cells from human PBMCs. In CB1R-positive cells, endocannabinoid ligands induced resistin expression via the p38-Sp1 pathway. In both mouse models, a high-fat diet increased the accumulation of endocannabinoid ligands in adipose tissue, which recruited the CB1R-positive cells that secrete resistin, leading to adipose tissue inflammation and insulin resistance. This phenomenon was suppressed by CB1R blockade or in resistin knockout mice. Interestingly, this process was accompanied by mitochondrial change that was induced by resistin treatment. These results provide important insights into the ECS-resistin axis, leading to the development of metabolic diseases. Therefore, the regulation of resistin via the CB1R could be a potential therapeutic strategy for cardiometabolic diseases.
RESUMEN
While many studies have explored dietary substitutes and mobile apps separately, a combined approach to metabolic dysfunction-associated steatotic liver disease (MASLD) has not been investigated. This study evaluated short-term mobile interventions coupled with partial meal replacement in patients with MASLD. Sixty adults with MASLD and a body mass index ≥25 kg/m2 from a health examination center were randomized into an intervention group using a mobile app with partial meal replacements or a control group receiving standard educational materials. Liver enzyme levels, lipid profiles, and anthropometric measurements were assessed at baseline and after 4 weeks. Twenty-five participants in the intervention group and 24 in the control group completed the trial. Significant reductions were observed in the intervention group for alanine aminotransferase (-28.32 versus [vs.] -10.67, p = 0.006) and gamma-glutamyl transferase (-27.76 vs. 2.79, p = 0.014). No significant changes in aspartate aminotransferase, body weight, or waist circumference were noted in the intervention group. Four weeks of mobile lifestyle intervention incorporating partial meal replacements improved liver enzyme profiles in patients with MASLD. This strategy demonstrated the potential for mitigating elevated liver enzyme levels without altering body weight or waist circumference. Comprehensive and longer-term research is needed to substantiate and elaborate these preliminary outcomes.
Asunto(s)
Alanina Transaminasa , Dieta Rica en Proteínas , Hígado , Aplicaciones Móviles , Humanos , Masculino , Femenino , Proyectos Piloto , Persona de Mediana Edad , Hígado/metabolismo , Alanina Transaminasa/sangre , Adulto , Estilo de Vida , Hígado Graso/terapia , Hígado Graso/dietoterapia , gamma-Glutamiltransferasa/sangre , Índice de Masa Corporal , Comidas , Aspartato Aminotransferasas/sangre , Pruebas de Función Hepática , AncianoRESUMEN
Thermoelectric devices have received significant attention because of their potential for sustainable energy recovery. In these devices, a thermal design that optimizes heat transfer and dissipation is crucial for maximizing the power output. Heat dissipation generally requires external active or passive cooling devices, which often suffer from inevitable heat loss and heavy systems. Herein, the design of heat-sink integrated thermoelectric legs is proposed to enhance heat dissipation without external cooling devices, realized by finite element model simulation and 3D printing of ternary silver chalcogenide-based thermoelectric materials. Owing to the self-induced surface charges of the synthesized AgBiSe2 (n-type) and AgSbTe2 (p-type) particles, these particle-based colloidal inks exhibited high viscoelasticity, which enables the creation of complex heat-dissipation architectures via 3D printing. Power generators made from 3D-printed heat-dissipating legs exhibit higher temperature differences and output power than traditional cuboids, offering a new strategy for enhancing thermoelectric power generation.
RESUMEN
Cytokines of the common-γ receptor chain (γc) family are crucial for T-cell differentiation and dysregulation of γc cytokine pathways is involved in the pathogenesis of autoimmune diseases. There is increasing evidence that the availability of the γc receptor (CD132) for the associated receptor chains has implications for T-cell functions. Here we studied the influence of differential γc expression on the expression of the IL-2Rα (CD25), the IL-7Rα (CD127) and the differentiation of activated naïve T cells. We fine-tuned the regulation of γc expression in human primary naïve T cells by lentiviral transduction using small hairpin (sh)RNAs and γc cDNA. Differential γc levels were then analysed for effects on T-cell phenotype and function after activation. Differential γc expression markedly affected IL-2Rα and IL-7Rα expression on activated naïve T cells. High γc expression (γc-high) induced significantly higher expression of IL-2Rα and re-expression of IL-7Rα after activation. Inhibition of γc caused lower IL-2Rα/IL-7Rα expression and impaired proliferation of activated naïve T cells. In contrast, γc-high T cells secreted significantly higher concentrations of effector cytokines (i.e., IFN-γ, IL-6) and showed higher cytokine-receptor induced STAT5 phosphorylation during initial stages as well as persistently higher pSTAT1 and pSTAT3 levels after activation. Finally, accelerated transition towards a CD45RO expressing effector/memory phenotype was seen especially for CD4+ γc-high naïve T cells. These results suggested that high expression of γc promotes expression of IL-2Rα and IL-7Rα on activated naïve T cells with significant effects on differentiation and effector cytokine expression.
Asunto(s)
Diferenciación Celular , Activación de Linfocitos , Humanos , Diferenciación Celular/inmunología , Subunidad gamma Común de Receptores de Interleucina/genética , Subunidad gamma Común de Receptores de Interleucina/metabolismo , Receptores de Interleucina-7/metabolismo , Receptores de Interleucina-7/genética , Células Cultivadas , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transducción de Señal , Fosforilación , Factor de Transcripción STAT5/metabolismo , Regulación de la Expresión GénicaRESUMEN
Promotion of myoblast differentiation by activating mitochondrial biogenesis and protein synthesis signaling pathways provides a potential alternative strategy to balance energy and overcome muscle loss and muscle disorders. Saururus chinensis (Lour.) Baill. extract (SCE) has been used extensively as a traditional herbal medicine and has several physiological activities, including antiasthmatic, antioxidant, antiinflammatory, antiatopic, anticancer and hepatoprotective properties. However, the effects and mechanisms of action of SCE on muscle differentiation have not yet been clarified. In the present study, it was investigated whether SCE affects skeletal muscle cell differentiation through the regulation of mitochondrial biogenesis and protein synthesis in murine C2C12 myoblasts. The XTT colorimetric assay was used to determine cell viability, and myosin heavy chain (MyHC) levels were determined using immunocytochemistry. SCE was applied to C2C12 myotube at different concentrations (1, 5, or 10 ng/ml) and times (1,3, or 5 days). Reverse transcriptionquantitative PCR and western blotting were used to analyze the mRNA and protein expression change of factors related to differentiation, mitochondrial biogenesis and protein synthesis. Treatment of C2C12 cells with SCE at 1,5, and 10 ng/ml did not affect cell viability. SCE promoted C2C12 myotube formation and significantly increased MyHC expression in a concentration and timedependent manner. SCE significantly increased the mRNA and protein expression of muscle differentiationspecific markers, such as MyHC, myogenic differentiation 1, myogenin, Myogenic Factor 5, and ßcatenin, mitochondrial biosynthesisrelated factors, such as peroxisome proliferatoractivated receptorgamma coactivator1α, nuclear respirator factor1, AMPactivated protein kinase phosphorylation, and histone deacetylase 5 and AKT/mTOR signaling factors related to protein synthesis. SCE may prevent skeletal muscle dysfunction by enhancing myoblast differentiation through the promotion of mitochondrial biogenesis and protein synthesis.
Asunto(s)
Diferenciación Celular , Biogénesis de Organelos , Extractos Vegetales , Proteínas Proto-Oncogénicas c-akt , Saururaceae , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Ratones , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Extractos Vegetales/farmacología , Línea Celular , Saururaceae/química , Supervivencia Celular/efectos de los fármacos , Mioblastos/metabolismo , Mioblastos/efectos de los fármacos , Mioblastos/citología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/citología , Cadenas Pesadas de Miosina/metabolismo , Cadenas Pesadas de Miosina/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/citologíaRESUMEN
Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by articular cartilage destruction, bone destruction and synovial hyperplasia. It has been suggested that Vigeo, a mixture of Eleutherococcus senticosus, Achyranthes japonica and Atractylodes japonica fermented with Korean nuruk, has an anti-osteoporotic effect in a mouse model of inflammation-mediated bone loss. The present study evaluated the therapeutic effects of Vigeo in RA using a collagen-induced arthritis (CIA) mouse model. DBA/1J mice were immunized with bovine type II collagen on days 0 and 21 and Vigeo was administered daily for 20 days beginning the day after the second type II collagen injection. The mice were sacrificed on day 42 and the joint tissues were anatomically separated and subjected to micro computed tomography and histological analyses. In addition, the serum levels of TNF-α, IL-6 and IL-1ß were determined by enzyme-linked immunosorbent assays. CIA in DBA/1J mice caused symptoms of RA, such as joint inflammation, cartilage destruction and bone erosion. Treatment of CIA mice with Vigeo markedly decreased the symptoms and cartilage pathology. In addition, radiological and histological analyses showed that Vigeo attenuated bone and cartilage destruction. The serum TNF-α, IL-6 and IL-1ß levels following oral Vigeo administration were also reduced when compared with those in CIA mice. The present study revealed that Vigeo suppressed arthritis symptoms in a CIA-RA mouse model, including bone loss and serum levels of TNF-α, IL-6 and IL-1ß.
RESUMEN
Porous thermoelectric materials offer exciting prospects for improving the thermoelectric performance by significantly reducing the thermal conductivity. Nevertheless, porous structures are affected by issues, including restricted enhancements in performance attributed to decreased electronic conductivity and degraded mechanical strength. This study introduces an innovative strategy for overcoming these challenges using porous Bi0.4Sb1.6Te3 (BST) by combining porous structuring and interface engineering via atomic layer deposition (ALD). Porous BST powder was produced by selectively dissolving KCl in a milled mixture of BST and KCl; the interfaces were engineered by coating ZnO films through ALD. This novel architecture remarkably reduced the thermal conductivity owing to the presence of several nanopores and ZnO/BST heterointerfaces, promoting efficient phonon scattering. Additionally, the ZnO coating mitigated the high resistivity associated with the porous structure, resulting in an improved power factor. Consequently, the ZnO-coated porous BST demonstrated a remarkable enhancement in thermoelectric efficiency, with a maximum zT of approximately 1.53 in the temperature range of 333-353 K, and a zT of 1.44 at 298 K. Furthermore, this approach plays a significant role in enhancing the mechanical strength, effectively mitigating a critical limitation of porous structures. These findings open new avenues for the development of advanced porous thermoelectric materials and highlight their potential for precise interface engineering through the ALD.
RESUMEN
Background and aims: Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Methods: Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. Results: We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). Conclusions: The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Infliximab/uso terapéutico , Resultado del Tratamiento , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Enfermedad de Crohn/tratamiento farmacológicoRESUMEN
PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios. EXPERIMENTAL DESIGN: The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model. RESULTS: We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood-brain barrier. CONCLUSIONS: Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood-brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.
Asunto(s)
Acrilamidas , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Ratones , Animales , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Resistencia a Antineoplásicos/genética , Compuestos de AnilinaRESUMEN
Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.
Asunto(s)
Electrónica , Neuronas , Animales , Ratones , Neuronas/fisiología , Encéfalo/fisiología , Cráneo/diagnóstico por imagen , Metales , Impresión TridimensionalRESUMEN
A male in his 60s presented to the emergency department (ED) with a 3-week history of fever and progressive confusion. Initial laboratory and radiographic workup was largely unremarkable except for moderate bilateral pleural effusions. The patient was admitted on broad-spectrum antibiotics and further workup for fever of unknown aetiology. The differential diagnosis was broadened to different zoonotic infections, and subsequent laboratory testing showed a markedly elevated Bartonella henselae IgG and Bartonella quintana IgG (1:4096 and 1:512, respectively) in addition to positive B. henselae IgM titre (>1:20). During hospitalisation, the patient became more hypoxic and was found to have enlarging pleural effusions as well as a new pericardial effusion. The patient was treated with intravenous then oral doxycycline 100 mg two times per day and oral rifampin 300 mg two times per day for 4 weeks with subsequent improvement in clinical status as well as both effusions. This case highlights a unique presentation of Bartonella and its rare manifestation of pleural and pericardial effusions.
Asunto(s)
Infecciones por Bartonella , Derrame Pericárdico , Derrame Pleural , Humanos , Masculino , Infecciones por Bartonella/complicaciones , Infecciones por Bartonella/diagnóstico , Infecciones por Bartonella/tratamiento farmacológico , Diagnóstico Diferencial , Inmunoglobulina G , Derrame Pericárdico/diagnóstico , Derrame Pleural/etiología , Derrame Pleural/diagnóstico , Persona de Mediana Edad , AncianoRESUMEN
Excessive bone-resorbing osteoclast activity during bone remodeling is a major feature of bone diseases, such as osteoporosis. Therefore, the inhibition of osteoclast formation and bone resorption can be an effective therapeutic target for various bone diseases. Gryllus biomaculatus (GB) has recently been approved as an alternative food source because of its high nutritional value and environmental sustainability. Traditionally, GB has been known to have various pharmacological properties, including antipyretic and blood pressure-lowering activity, and it has recently been reported to have various biological activities, including protective effects against inflammation, oxidative stress, insulin resistance, and alcohol-induced liver injury. However, the effect of GB on osteoclast differentiation and bone metabolism has not yet been demonstrated. In this study, we confirmed the inhibitory effect of GB extract (GBE) on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. To determine the effect of GBE on RANKL-induced osteoclast differentiation and function, we performed TRAP and F-actin staining, as well as a bone-resorbing assay. The intracellular mechanisms of GBE responsible for the regulation of osteoclastogenesis were revealed by Western blot analysis and quantitative real-time polymerase chain reaction. We investigated the relationship between GBE and expression of osteoclast-specific molecules to further elucidate the underlying mechanisms. It was found that GBE significantly suppressed osteoclastogenesis by decreasing the phosphorylation of Akt, p38, JNK, and ERK, as well as Btk-PLCγ2 signaling, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos, NFATc1, and osteoclastogenesis-specific marker genes. Additionally, GBE inhibited the formation of F-actin ring-positive osteoclasts and bone resorption activity of mature osteoclasts. Our findings suggest that GBE is a potential functional food and therapeutic candidate for bone diseases involving osteoclasts.
Asunto(s)
Resorción Ósea , Osteoclastos , Ligando RANK , Humanos , Actinas/metabolismo , Resorción Ósea/tratamiento farmacológico , Diferenciación Celular , Ligandos , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Ligando RANK/antagonistas & inhibidores , Ligando RANK/metabolismoRESUMEN
Chlorine (Cl)-containing chemicals, including hydrogen chloride, generated during thermal degradation of polyvinyl chloride (PVC) and corresponding mixture impede the chemical recycling of PVC-containing plastic wastes. While upgrading plastic-derived vapors, the presence of Cl-containing chemicals may deactivate the catalysts. Accordingly, herein, catalytic upgrading of pyrolysis vapor prepared from a mixture of PVC and polyolefins is performed using a fixed-bed reactor comprising zeolites. Among the H-forms of zeolites (namely, ZSM-5, Y, ß, and chabazite) used in this study, a higher yield of gas products composed of hydrocarbons with lower carbon numbers is obtained using H-ZSM-5, thus indicating further decomposition of the pyrolysis vapor to C1-C4 hydrocarbons on it. Although the formation of aromatic compounds is better on H-ZSM-5, product distributions can be adjusted by further modifying the acidic properties via the alteration of the Si/Al molar ratio, and maximum yields of C1-C4 compounds (60.8%) and olefins (64.7%) are achieved using a Si/Al molar ratio of 50. Additionally, metal ion exchange on H-ZSM-5 is conducted, and upgrading of PVC-containing waste-derived vapor to aromatic chemicals and small hydrocarbon molecules was successfully performed using Co-substituted H-ZSM-5. It reveals that the highest yield of gas products on 1.74 wt% cobalt (Co)-substituted H-ZSM-5 is acquired via the selection of an appropriate metal and metal ion concentration adjustment. Nevertheless, introduction of excess Co into the H-ZSM-5 surface decreases the cracking activity, thereby implying that highly distributed Co is required to achieve excellent cracking activity. The addition of Co also adjusted the acid types of H-ZSM-5, and more Lewis acid sites compared to Brønsted acid sites selectively produced olefins and naphthenes over paraffins and aromatics. The proposed approach can be a feasible process to produce valuable petroleum-replacing chemicals from Cl-containing mixed plastic wastes, contributing to the closed loops for upcycling plastic wastes.
Asunto(s)
Cloro , Zeolitas , Zeolitas/química , Hidrocarburos , Alquenos/química , CatálisisRESUMEN
There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson's ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 µm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays.
RESUMEN
Developing soft robots that can control their own life cycle and degrade on-demand while maintaining hyperelasticity is a notable research challenge. On-demand degradable soft robots, which conserve their original functionality during operation and rapidly degrade under specific external stimulation, present the opportunity to self-direct the disappearance of temporary robots. This study proposes soft robots and materials that exhibit excellent mechanical stretchability and can degrade under ultraviolet light by mixing a fluoride-generating diphenyliodonium hexafluorophosphate with a silicone resin. Spectroscopic analysis revealed the mechanism of SiâOâSi backbone cleavage using fluoride ion (F-) and thermal analysis indicated accelerated decomposition at elevated temperatures. In addition, we demonstrated a robotics application by fabricating electronics integrated gaiting robot and a fully closed-loop trigger disintegration robot for autonomous, application-oriented functionalities. This study provides a simple yet novel strategy for designing life cycle mimicking soft robotics that can be applied to reduce soft robotics waste, explore hazardous areas, and ensure hardware security with on-demand destructive material platforms.
RESUMEN
Background: Detecting high-risk arrhythmia is important in diagnosing patients with palpitations. We compared the diagnostic accuracies of 7-day patch-type electrocardiographic (ECG) monitoring and 24-h Holter monitoring for detecting significant arrhythmias in patients with palpitations. Methods: This was a single-center prospective trial with 58 participants who presented with palpitations, chest pain or syncope. Outcomes were defined as the detection of any one of six arrhythmias, including supraventricular tachycardia (SVT), atrial fibrillation or atrial flutter lasting more than 30 s, pauses of more than 3 s, high-degree atrioventricular block, ventricular tachycardia (VT) >3 beats, or polymorphic VT/ventricular fibrillation. The McNemar test for paired proportions was used to compare arrhythmia detection rates. Results: The overall arrhythmia detection rate was higher with 7-day ECG patch monitoring than with 24-h Holter monitoring (34.5% vs. 19.0%, p = .008). Compared with the use of 24-h Holter monitors, the use of 7-day ECG patch monitors was associated with higher detection of SVT (29.3% vs. 13.8%, p = .042). No serious adverse skin reactions were reported among the ECG patch-monitored participants. Conclusions: The results suggest that a 7-day patch-type continuous ECG monitor is more effective for the detection of supraventricular tachycardia than is a 24-h Holter monitor. However, the clinical significance of device detected arrhythmia should be consolidated.