To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS).
Phase 1 randomised, ...double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed.
Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively.
The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.
To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS).
This ...open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group).
Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively.
This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment.
NCT01571206; Results.
Health-related quality of life (HRQOL) in patients with fibromyalgia (FM) is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no ...study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM).
HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ) was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Arthritis Self-Efficacy Scale (ASES), and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software.
Of the 336 patients, 301 (89.6%) were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ2 = 2.336, df = 3, p = 0.506). The final model showed that Physical Component Summary (PCS) was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS) was inversely related to FIQ, BDI, and STAI.
In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is an environment that provides various biological ...niches, such as the teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome also plays an important role in the triggering, development, and progression of oral and systemic diseases. In recent years, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology and is overwhelmingly promising compared to the previous era. It has been found that patients with oral and systemic diseases have variations in their oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that the oral microbiome plays in influencing oral and systemic diseases and furthers the knowledge related to the oral microbiome produced over the past 30 years. A wide range of updates were provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and can help to develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.
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The relationship between body mass index (BMI) and mortality remains controversial. Furthermore, the association between BMI and cardiovascular events (CVE) is not conclusive and may differ by ...ethnicity. We aimed to estimate the associations between the BMI and mortality or cardiovascular disease in a general Korean population.
This study was based on a sample cohort database released by the Korean National Health Insurance Service. We analyzed a total of 415,796 adults older than 30 years of age who had undergone a national health examination at least once from 2002 to 2012. Hazard ratios for death and cardiovascular events were calculated using Cox proportional hazards models.
For both men and women, BMI and overall mortality showed a U-shaped association, with the lowest mortality rate among those with a BMI of 25-27.4 kg/m2. Compared with them, subjects with a BMI ≥ 30kg/m2, men with a BMI < 25 kg/m2, and women with a BMI < 22.5 kg/m2 showed significantly higher overall mortality. Additionally, men with a BMI < 22.5 kg/m2 and women with a BMI < 20 kg/m2 displayed an increased risk of cardiovascular mortality. Unlike the mortality trend, the CVD events trend showed a linearly positive association. The risk of a CVE was the lowest in men with a BMI ranging from 20 to 22.4 kg/m2 and in women with a BMI < 20 kg/m2.
The BMI showed a U-shaped association with overall mortality, where slightly obese subjects showed the lowest rate of mortality. The CVE exhibited a linear association with the BMI, where the lowest risk was observed for normal weight subjects in a general Korean population.
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To investigate the role of genetic predisposition in the pathogenesis of polycystic ovary syndrome (PCOS) in relation to obesity, we performed a genome-wide association study of PCOS in Koreans ...(n=1741). PCOS is a heterogeneous endocrinal disorder of uncertain etiology. Obesity is one of the well-known risk factors for PCOS. Genome-wide association study. Women with or without PCOS. A total of 1881 samples were genotyped using Illumina HumanOmni1 Quad v1 and processed by R packages. The PCOS patients were divided into two subgroups according to PCOS diagnostic criteria (Rotterdam and National Institutes of Health (NIH)). For PCOS-associated loci in the two definitions, we successfully confirmed significant associations of GYS2 for body mass index in the discovery stage. We further replicated pleiotropic associations of GYS2 in a childhood obesity study (n=482) and in a gestational diabetes study (n=1710), respectively. Our study provides a preliminary framework upon diverse genetic effects underlying PCOS in Korean women. A newly identified GYS2 gene as a predisposing factor of PCOS might expand understanding of the biological pathways in metabolic and endocrine regulation.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mn-doped sodium iron fluorophosphates Na 2 Fe 0.9 Mn 0.1 PO 4 F were synthesized using ball milling via a solid-state reaction route. The crystal structure and magnetic properties of the as-prepared ...materials were studied by using X-ray diffraction (XRD), superconducting quantum interference device (SQUID), and Mössbauer spectroscopy. Structural refinement of Na 2 Fe 0.9 Mn 0.1 PO 4 F was analyzed using the Fullprof program. From the XRD patterns, the crystal structure was found to be orthorhombic with the space group Pbcn . Na 2 Fe 0.9 Mn 0.1 PO 4 F has a 2-D layered structure composed of a pair of Fe(Mn)O 4 F 2 octahedrons through fluorine ion sharing, similar to that of Na 2 FePO 4 F. The temperature dependence of the zero-field-cooled (ZFC) and field-cooled (FC) curves was measured at temperatures ranging from 1.8 to 295 K under an applied field of 100 Oe. We confirmed that the Néel temperature was 2.5 K, which is lower than that of Na 2 FePO 4 F (<inline-formula> <tex-math notation="LaTeX">T_{N} =3.4 </tex-math></inline-formula> K). Mössbauer spectroscopy measurements at 4.2-295 K were conducted. At all the temperatures, the spectra were fitted with a double and were determined to be Fe 2+ ions based on an isomer shift (<inline-formula> <tex-math notation="LaTeX">\delta </tex-math></inline-formula>). In addition, the large value of the electric quadrupole splitting (<inline-formula> <tex-math notation="LaTeX">\Delta E_{Q} </tex-math></inline-formula>) is explained by the asymmetric local environment of the Fe ions.
Spin pumping and the spin transfer torque in the normal metal (NM)/ferromagnetic materials (FM) heterostructure strongly depend on the interfacial spin memory loss. Therefore, the interface ...engineering of the NM/FM bilayer is important for enhancing spin pumping and spin-orbit torque efficiency for spin-orbitronic devices.
In this study, we investigate the influence of the graphene interlayer between Pt and yttrium iron garnet (YIG) on spin pumping. Measurements of both the coplanar wave guide ferromagnetic resonance and inverse spin Hall effect with ferromagnetic resonance are performed to study the role of graphene in the transmission of the spin current at the interface. Results indicate a decreased Gilbert damping constant with the insertion of graphene interlayer, which causes the spin mixing conductance and inverse spin Hall voltage to be significantly reduced. The observed decrease in damping constant and spin injection is attributed to the presence of magnetic proximity effect and interfacial spin-orbit scattering, which causes graphene to serve as a spin-sink layer.
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•Introduction of graphene interlayer between Pt and yttrium iron garnet (YIG) heterostructures.•Investigation of interface engineering by ferromagnetic resonance and inverse spin Hall voltage measurements.•Reduction of spin mixing conductance and the inverse spin Hall voltage by the insertion of a graphene layer.•Graphene at the interface of Pt/YIG behaves as a spin-sink layer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Interfacial magnetic interactions between different elements are the origin of various spin-transport phenomena in multi-elemental magnetic systems. We investigate the coupling between the magnetic ...moments of the rare-earth, transition-metal, and heavy-metal elements across the interface in a GdFeCo/Pt thin film, an archetype system to investigate ferrimagnetic spintronics. The Pt magnetic moments induced by the antiferromagnetically aligned FeCo and Gd moments are measured using element-resolved x-ray measurements. It is revealed that the proximity-induced Pt magnetic moments are always aligned parallel to the FeCo magnetic moments, even below the ferrimagnetic compensation temperature where FeCo has a smaller moment than Gd. This is understood by a theoretical model showing distinct effects of the rare-earth Gd 4f and transition-metal FeCo 3d magnetic moments on the Pt electronic states. In particular, the Gd and FeCo work in-phase to align the Pt moment in the same direction, despite their antiferromagnetic configuration. The unexpected additive roles of the two antiferromagnetically coupled elements exemplify the importance of detailed interactions among the constituent elements in understanding magnetic and spintronic properties of thin film systems.
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