Objective: A prospective trial suggests target infliximab trough levels of 3-7 μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce.
Aim: To explore ...whether high infliximab trough levels (≥7 μg/mL) are more effective and still safe.
Material and methods: In this cohort study of 183 patients (109 Crohn's disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 μg/mL during 420 patient-years.
Results: Fecal calprotectin and C-reactive protein (median interquartile range) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg 30-257; C-reactive protein 3 mg/L 3-3) compared to trough levels below 7 μg/mL (fecal calprotectin 155 mg/kg 72-474; C-reactive protein 3 mg/L 3-14.5) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 μg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 12.4%) compared to quadrimesters with trough levels <7 μg/mL (32/344 9.3%) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2-54%) increase of infliximab consumption.
Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.
Abstract
This study determined the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs)-enriched hen eggs consumption on immunoglobulin G (IgG) and total plasma protein N-glycan profiles and ...inflammatory biomarkers level in healthy individuals (N = 33) and cardiovascular (CV) patients (N = 21). Subjects were divided to Control-Healthy and Control-CV subgroups consumed three regular hens’ eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs-Healthy and n-3 PUFAs-CV subgroups consumed three n-3 PUFAs-enriched hen eggs/daily (1053 mg n-3 PUFAs/day) for 3 weeks. Serum-free fatty acids profile and high-sensitivity C-reactive protein, interleukin 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha were measured. Total plasma protein and IgG N-glycome have been profiled before and after dietary protocols. Serum n-3 PUFAs concentration significantly increased following n-3 PUFAs hen eggs consumption in both n-3 PUFAs-Healthy and n-3 PUFAs-CV. IL-10 significantly increased in both Healthy subgroups, whereas no change occurred in CV subgroups. Derived IgG N-glycan traits: bisecting N-acetylglucosamine (B) significantly decreased in n-3 PUFAs-Healthy, whereas agalactosylation (G0) and core fucosylation (CF) significantly increased in Control-Healthy. Derived total plasma protein N-glycan traits: high branching glycans, trigalactosylation, tetragalactosylation, trisialylation, tetrasialylation and antennary fucosylation significantly decreased, whereas G0, monogalactosylation (G1), neutral glycans (S0), B, CF and oligomannose structures significantly increased in n-3 PUFAs-CV. Digalactosylation significantly decreased, and G0, G1, S0, disialylation, B and CF significantly increased in Control-CV. n-3 PUFAs consumption alters IgG N-glycan traits and IL-10 in healthy individuals, and total plasma protein N-glycan traits in CV patients, by shifting them toward less inflammatory N-glycosylation profile.
The study deals with a three-storey log house located in the suburbs of Ljubljana, Slovenia (temperate climate). Firstly, the calibrated thermal model of the log house was defined. The calibrated ...model had an hourly NMBE between −2.12 % and 1.84 % and a CV(RMSE) between 3.16 % and 3.57 %. Then, the adaptive thermal comfort during the warmer part of the year was assessed according to EN 16798-1 and future climate (SRES A2 scenario). Additionally, various building-related and organisational measures for overheating prevention were evaluated. It was found that the most effective measures to prevent overheating are the organisational measures of shading activation and night ventilation. It was demonstrated that the efficiency of night ventilation would even improve over time. Thus, at the end of the 21
st
century, discomfort hours could be reduced by 67 % compared to the baseline. In contrast, building-related measures have a significant effect only when combined with organisational measures. Overall, in 2071–2100 adaptive thermal comfort was improved most when the measure of increased thermal insulation was coupled with shading and night ventilation, resulting in 1053 discomfort hours less than the baseline case.
In this letter, a novel low-complexity modulation for capacitive coupled human body communications (CC-HBCs) is proposed. Called inductance index modulation, the proposed method refers to the channel ...conditions between transmitters and receivers that are used as a new signal space. Precisely, at the transmitter side, one of the <inline-formula> <tex-math notation="LaTeX">{M=2^{n}} </tex-math></inline-formula> inductances is selected according to the incoming <inline-formula> <tex-math notation="LaTeX">{n} </tex-math></inline-formula> bits, in order to change the CC-HBC channel condition between transmitters and receivers. Then, at the receiver side, the transmitted bits are predicted by estimating the CC-HBC channel conditions using the maximum likelihood detector. The CC-HBC channel is modeled using the transfer function method. The bit error rate performance of the proposed scheme is compared with conventional modulations, yielding a very promising approach.
Neurodegenerative conditions significantly impact patient quality of life. Many conditions do not have a cure, but with appropriate and timely treatment the advance of the disease could be ...diminished. However, many patients only seek a diagnosis once the condition progresses to a point at which the quality of life is significantly impacted. Effective non-invasive and readily accessible methods for early diagnosis can considerably enhance the quality of life of patients affected by neurodegenerative conditions. This work explores the potential of convolutional neural networks (CNNs) for patient gain freezing associated with Parkinson’s disease. Sensor data collected from wearable gyroscopes located at the sole of the patient’s shoe record walking patterns. These patterns are further analyzed using convolutional networks to accurately detect abnormal walking patterns. The suggested method is assessed on a public real-world dataset collected from parents affected by Parkinson’s as well as individuals from a control group. To improve the accuracy of the classification, an altered variant of the recent crayfish optimization algorithm is introduced and compared to contemporary optimization metaheuristics. Our findings reveal that the modified algorithm (MSCHO) significantly outperforms other methods in accuracy, demonstrated by low error rates and high Cohen’s Kappa, precision, sensitivity, and F1-measures across three datasets. These results suggest the potential of CNNs, combined with advanced optimization techniques, for early, non-invasive diagnosis of neurodegenerative conditions, offering a path to improve patient quality of life.
A coil-type photoelectrocatalytic microreactor for efficient and clean water purification.
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A continuous-flow, coil-type photoelectrocatalytic microreactor for the degradation of ...caffeine was designed, assembled and characterized. Its main components are the photocatalytically active anode and the cathode coils, which are wrapped around a silica-glass rod and placed into a UV-transparent housing. The anode coil was prepared by anodic oxidation of the titanium coil, which leads to the formation of vertically aligned, titanium dioxide, nanotube arrays that exhibit a high photocatalytic activity and are rigidly attached to the titanium wire. The photocatalytic, electrocatalytic and photoelectrocatalytic activities of the assembled microreactor were measured systematically while changing the main parameters that affect the device’s efficiency. The most significant change in the microreactor’s design in terms of efficiency was to place the cathode coils on both sides of the anode coil, which resulted in the shortest time for complete degradation of the caffeine. When an applied anodic bias potential of 4V was used in the most efficient microreactor design, 1mL of the 40mg/L caffeine was fully decomposed in 55min.
We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human ...diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the
hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys.
The importance of oral microflora composition in HIV-infected patients is well recognized. However, no studies so far have dealt with age-related changes in periodontal pathogens occurrence in HIV+ ...individuals. The aim of the present study was to assess and compare temporal changes of bacteria frequency in younger (≤35 years) and older (≥50 years) HIV-infected and non-infected individuals. Bacterial DNA was isolated from buccal swabs of 30 younger and 30 older subjects in both HIV+ and HIV- groups. By means of PCR the following microorganisms were detected: Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Peptostreptococcus micros, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola. Oral and periodontal examinations were performed in all subjects. The prevalence of microorganisms was significantly higher in HIV+ patients compared to controls, and their distribution showed a notable shift. The decreasing incidence in HIV- subjects was: Pi>Pm>Pg>Aa>Ec>Tf>Td whilst in HIV+ it was: Pi>Pm>Ec>Pg>Tf>Aa>Td. Oral manifestations of HIV infection were more frequent in older compared to younger patients. All measured values of clinical periodontal parameters were significantly higher in older compared to younger HIV+ patients. Ageing in HIV+ subjects is accompanied with a substantial increase and rearrangements of periodontal microflora, potentially aggravating oral and systemic health.
To assess sex-related differences in forearm skin microvascular reactivity to vascular occlusion and cardiovascular health in young healthy women and men.
203 young healthy individuals (67 men/136 ...women) participated in this study. Post-occlusive reactive hyperemia (PORH) in skin microcirculation following 1', 2' and 3' vascular occlusion period was assessed using laser Doppler flowmetry. Anthropometric parameters, body composition, blood pressure, heart rate and biochemical parameters were measured in all participants. Correlations between PORH and measured parameters were determined by using corresponding tests.
Women had significantly higher forearm PORH following 1', 2' and 3' vascular occlusion than men. Women had lower body mass index and waist-to-hip ratio, but higher fat mass than men. Men had significantly higher blood pressure and lower heart rate than women. Also, women had lower hemoglobin, urea, creatinine and serum uric acid, but higher HDL cholesterol level than men. PORH was negatively associated with waist-to-hip ratio and systolic blood pressure only in women.
Young healthy women exhibit higher skin microvascular reactivity to vascular occlusion compared to age-matched men. Increased systolic blood pressure or central obesity (waist-to-hip ratio) may pose greater risk to young healthy women than men by adversely affecting peripheral microvascular function.
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