Evidence Of Reactivity Research Articles

High-affinity CD8 variants enhance the sensitivity of pMHCI antigen recognition via low-affinity TCRs

CD8+ T cell-mediated recognition of peptide-major histocompatibility complex class I (pMHCI) molecules involves cooperative binding of the T cell receptor (TCR), which confers antigen specificity, and the CD8 coreceptor, which stabilizes the TCR/pMHCI complex. Earlier work has shown that the sensitivity of antigen recognition can be regulated in vitro by altering the strength of the pMHCI/CD8 interaction. Here, we characterized two CD8 variants with moderately enhanced affinities for pMHCI, aiming to boost antigen sensitivity without inducing non-specific activation. Expression of these CD8 variants in model systems preferentially enhanced pMHCI antigen recognition in the context of low-affinity TCRs. A similar effect was observed using primary CD4+ T cells transduced with cancer-targeting TCRs. The introduction of high-affinity CD8 variants also enhanced the functional sensitivity of primary CD8+ T cells expressing cancer-targeting TCRs, but comparable results were obtained using exogenous wild-type CD8. Specificity was retained in every case, with no evidence of reactivity in the absence of cognate antigen. Collectively, these findings highlight a generically applicable mechanism to enhance the sensitivity of low-affinity pMHCI antigen recognition, which could augment the therapeutic efficacy of clinically relevant TCRs.

Swift Heavy Ion-Induced Reactivity and Surface Modifications in Indium Thin Films.

As an energetic ion traverses a target material, it loses its energy through the processes of electronic energy loss (Se) and nuclear energy loss (Sn). Controlled swift heavy ion (SHI) irradiation on solid targets produces its effects through both of these mechanisms, as a consequence of which modifications occur in the structure, surface morphology, and magnetic and optical properties, apart from ion implantation and ion-induced reactivity. A systematic investigation of these effects can be useful in developing standard protocols for creating desired effects in materials using specific ion beams. In this study, indium films of thickness 25 nm were deposited on silicon substrates and were subjected to 100 MeV O7+ and 100 MeV Si7+ ion irradiation, with the fluences varying from 1 × 1011 to 1 × 1013 ions/cm2. The pristine and SHI-irradiated films were then characterized using glancing incidence X-ray diffraction (GIXRD), Rutherford backscattering spectrometry (RBS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The motive was to identify the effects of irradiation with different ion species having large variations in electronic and nuclear energy losses. While the RBS results suggest that sputtering is extremely low and that there are no major changes in the film composition due to ion beam-induced mixing, the GIXRD analysis indicates that increasing the ion fluence reduces the crystallinity of the film for both the ions. Ion beam irradiation with O7+ ions, however, results in beam-induced reactivity, as the GIXRD scan shows characteristic peaks from indium oxide (In2O3), which become the predominant peaks at the highest fluence used here. Si7+ ion irradiation results in a narrowing of the particle size distribution on the surface, with no evidence of reactivity. SEM results indicate fusion and fragmentation of grains with the increase in the ion fluences, and AFM images reveal an increase in the surface roughness of a few percent when irradiated with both 100 MeV O7+ and 100 MeV Si7+ ions.

P146 Hepatitis E infection in rheumatic disease: no evidence of chronicity

Abstract Background/Aims Hepatitis E virus [HEV] is the most common cause of acute hepatitis in developing countries but rare in the industrialised world. In the vast majority it causes an acute self-limiting infection which is often asymptomatic. It is usually detected due to raised transaminases in liver function tests [LFTs] which are checked as part of DMARD monitoring. There is increasing literature that immunocompromised patients with human immunodeficiency virus or transplant recipients are at risk of developing chronic HEV infection, which can progress to liver failure. It is unclear that immunosuppressed patients who have a rheumatological conditions have similar issues, which we have looked into locally. Chronic infection is defined as having detectable RNA for over 3 months. Methods Retrospective review of patients attending rheumatology outpatient clinic for blood monitoring, who had positive Hepatitis E serology between 2010 and 2021. Results We identified nine patients attending the rheumatology clinic in Sheffield, confirmed as having acute infection with HEV as Hep E IgM antibody was positive. They were all on immunosuppression and hence having regular monitoring bloods and were receiving either prednisolone, DMARDS or biologics or in combination. There were five males and four females, with an age range of 38 to 71 years. Eight patients had acutely abnormal LFTs with a peak ALT [normal <41 IU/L] ranging from 59 to 1651 while in one the LFTs remained normal. Eight out of nine patient's LFTs recovered to baseline over a period ranging from 3 to 6 weeks (one moved out of area). Five patients had HEV RNA tested after the positive IgM. Two patients had HEV RNA detected initially, the rest had undetectable RNAs. Repeat RNA testing 2 months later was undetectable in both patients, suggesting no chronic HEV infection in all patients. No patients were given HEV antiviral treatment. Almost all patients had their immunosuppressant treatment paused, which was recommenced once their LFTs normalised. In all patients LFTs have remained normal even after 5 years with no evidence of reactivation in spite of ongoing immunosuppression. We plan to check HEV RNA if the LFTs were to become abnormal. Conclusion Our case series raises awareness that rheumatologists should consider HEV as a differential in patients with a marked unexpected rise in transaminases. We observed that all our patients cleared HEV infection and there was no evidence of chronicity even with ongoing immunosuppression, which is different from Hepatitis B & C. We recommend that immunosuppressant treatment should be stopped initially following HEV infection and reintroduced once LFTs have normalised and HEV RNA is undetectable. Disclosure C.A. Zollinger-Read: None. M. Raza: None. M.F. Kazmi: None.

Examining reactivity to the measurement of physical activity and sedentary behavior among women in midlife with elevated risk for cardiovascular disease

Objectives To estimate the extent of reactivity to measurement of physical activity (PA) and sedentary behavior among women in midlife with elevated risk for cardiovascular disease (CVD). Design Secondary analysis of a 10-day observational study of PA and sedentary behavior. Main Outcome Measures PA (steps, minutes of light PA, total minutes of moderate-to- vigorous PA [MVPA]) and percent time in sedentary behavior per day were assessed using ActiGraph GT3X tri-axial accelerometers in 75 women in midlife with elevated CVD risk (e.g. hypertension; MAge = 51.61, MBMI = 34.02 kg/m2). Two-level multilevel models were used to test for evidence of reactivity, with the addition of random effects to test for evidence of individual differences in observed trends. Results All outcomes showed linear trends across days (ps < 0.001), though this masked what appeared to be meaningful dropoff after Day 1 or Day 2 (with little difference between subsequent days; srs ranging from 0.15 to 0.32). The random effect was significant only for percent time in sedentary behavior (χ 2[1] = 10.40, p = 0.02). Conclusions Consistent small to medium effects were found for all PA and sedentary behavior outcomes, underscoring the importance of considering measurement reactivity in populations with elevated CVD risk.

Erratum: Evidence for reactivation of new faults and seismicity migration away from the causative fault of the 2001 MW 7.7 Bhuj earthquake, western India

Erratum: Evidence for reactivation of new faults and seismicity migration away from the causative fault of the 2001 <i>M</i>W 7.7 Bhuj earthquake, western India

Treatment of a giant hepatic echinococcal cyst with percutaneous drainage and in vivo assessment of the protoscolicidal effect of praziquantel

Therapy choices for cystic echinococcisis (CE) are stage-specific: surgical, minimally invasive, medical or observation without intervention. PAIR (percutaneous aspiration, instillation of a scolicide, and re-aspiration) has been considered the treatment of choice for uncomplicated echinococcal liver cysts. However, PAIR carries the risk of toxic cholangitis or hypernatremia and that the cyst frequently refills with bile after withdrawing the catheter. We treated a patient with a giant CE 1 liver cyst with puncture drainage (PD) under albendazole coverage. Drainage enabled us to monitor the morphology of protoscolices under praziquantel (PZQ) co-medication. Protoscolices degenerated within 5 days of PZQ 50 mg/kg/d. The cyst cavity solidified with no evidence of reactivation or secondary spread. Percutaneous treatments can replace surgery in a significant number or cases with hepatic CE. PD allows to assess microscopically the viability of protoscolices under co-medication with PZQ–albendazole and to avoid the instillation of topical scolicides.

Does Reactivity To Accelerometry Occur In A Single Swimming Trial? A Randomized, Crossover Study

PURPOSE: Recent research has suggested that awareness of being monitored can influence the habitual physical activity behaviour of participants. This reactivity effect appears to also occur in single bouts of physical activity. However, it is presently unknown whether this acute reactivity effect exists in aquatic environments. The purpose of this study was, therefore, to test the hypothesis that reactivity would also occur in water-based studies. METHODS: Fifty-six healthy, recreational swimmers (31 men, age 22 ± 2 yr; 25 women, age 22 ± 1 yr) volunteered to participate in this ethically approved study. On two separate occasions, the participants randomly completed a 20-min swimming bout at a self-selected pace wearing (A) or not wearing (NA) a head-mounted accelerometer. Evidence of reactivity was defined as a statistically significant change in swimming distance covered (in m) in the A condition compared with the NA condition. Situational motivation, perceived performance, and perceived exertion were also assessed in both A and NA conditions. RESULTS: Swimming distance covered was longer (829 ± 202 vs. 811 ± 204 m) and perceived exertion was more strenuous (13.0 ± 2.4 vs. 12.2 ± 2.1) during the A condition compared with the NA condition (P < 0.05). Perceived performance and situational motivation were not significantly different between conditions (P > 0.05). CONCLUSIONS: These results indicate that the acute reactivity effect is likely to be present in aquatic environments and may threaten the internal validity of physical activity assessments in water-based studies.

Isolating the contribution of perceptual fluency to judgments of learning (JOLs): Evidence for reactivity in measuring the influence of fluency.

Judgments of learning (JOLs) refer to explicit predictions regarding the likelihood of remembering newly acquired information on a later test of memory. In recent years, there has been considerable interest in understanding the processes that underlie such judgments. Recent theorizing on this matter has characterized JOLs as inferential in nature-that is, they are derived from the implicit utilization of a variety of different cues of which only some are diagnostic of future memory performance. The present series of experiments examine the potential role for one such cue, namely, perceptual fluency (i.e., the subjective ease of perceiving a stimulus) in guiding JOLs. Using a novel methodological approach adapted from Masson (1986), we demonstrate across 6 experiments that perceptual fluency per se can indeed inform predictions of future memory performance, but that its influence depends on the specific task requirements at the time JOLs are solicited. We discuss these results in relation to experience- versus theory-based contributions to metamemory judgments. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Development and application of a combined molecular and tissue culture-based approach to detect latent infectious laryngotracheitis virus (ILTV) in chickens

Infectious laryngotracheitis virus (ILTV) causes severe respiratory disease in chickens. ILTV can establish latency and reactivate later in life, but there have been few investigations of ILTV latency. This study aimed to contribute to the methodologies available to detect latent ILTV. A nested PCR was developed which was more sensitive than three other molecular methods investigated in this study. This nested PCR was then used in conjunction with in vitro reactivation culture methods that were optimized and applied to trigeminal ganglia (TG) and tracheal samples from ILTV-vaccinated commercial layer birds (n = 30). ILTV DNA was detected by nested PCR in the upper respiratory tract (URT) or eye of 22 birds. Of the remaining 8 birds, ILTV could be detected by co-culture in TG of 5 birds, with reactivated virus mostly detected 6 days post-explant (dpe). ILTV was also detected in tracheal cultures by 6 dpe. In the ILTV-positive URT samples, the virus could be characterised as vaccine strains SA2 (n = 9) or A20 (n = 5). This study provides evidence for reactivation and shedding of vaccine ILTV in commercial layer birds. Moreover, this study produced a molecular and in-vitro culture method to detect latent viral infection.

Evidence of reactivation of a hydrothermal system from seismic anisotropy changes

Seismic velocity measurements have revealed that the Tohoku-Oki earthquake affected velocity structures of volcanic zones far from the epicenter. Using a seismological method based on ambient seismic noise interferometry, we monitored the anisotropy in the Mount Fuji area during the year 2011, in which the Tohoku-Oki earthquake occurred (Mw = 9.0). Here we show that even at 400 km from the epicenter, temporal variations of seismic anisotropy were observed. These variations can be explained by changes in the alignment of cracks or fluid inclusions beneath the volcanic area due to stress perturbations and the propagation of a hydrothermal fluid surge beneath the Hakone hydrothermal volcanic area. Our results demonstrate how a better understanding of the origin of anisotropy and its temporal changes beneath volcanoes and in the crust can provide insight into active processes, and can be used as part of a suite of volcanic monitoring and forecasting tools.

Differential reporting of fruit and vegetable intake among youth in a randomized controlled trial of a behavioral nutrition intervention

BackgroundNutrition interventions typically rely on self-reported intake that may be susceptible to differential reporting bias due to exposure to the intervention. Such differences may result from increased social desirability, increased attention to eating or improved recall accuracy, and may bias estimates of the intervention effect. This study investigated differential reporting bias of fruit and vegetable intake in youth with type 1 diabetes participating in a randomized controlled trial targeting increased whole plant food intake.MethodsParticipants (treatment n = 66, control n = 70) completed 3-day food records at baseline, 6-,12-, and 18-months, from which fruit and vegetable intake (servings/day) was calculated. Serum carotenoids were assessed at these visits using a high-performance liquid chromatography-based assay. Linear regression estimated associations of fruit and vegetable intake with serum carotenoids by treatment assignment. Multiplicative interaction terms tested the interaction of treatment assignment with fruit and vegetable intake on serum carotenoids for each visit and within each group over time.ResultsThe association of fruit and vegetable intake with serum carotenoids was significantly lower in the control versus intervention group at baseline (β = 0.22 Vs 0.46) and 6-month visits (β = 0.37 Vs 0.54), as evidenced by significant interaction effects. However, the association of fruit and vegetable intake with serum carotenoids did not significantly differ over time for either group.ConclusionsWhile the stronger association of fruit and vegetable with carotenoids in the treatment arm suggests greater reporting accuracy, this difference was evident at baseline, and did not change significantly over time in either group. Thus, results indicate greater subject-specific bias in the control arm compared to the treatment, and lack of evidence for reactivity to the intervention by treatment assignment.Clinical trial registry number and websiteNCT00999375

Evidence of Reactivity in the Membrane for the Unstable Monochloramine during MIMS Analysis.

Membrane Inlet Mass Spectrometry (MIMS) was used to analyze monochloramine solutions (NH2Cl) and ammonia solutions in a compact FTICR. Chemical ionization enables identification and quantification of the products present in the permeate. The responses of protonated monochloramine and ammonium increase linearly with the solution concentration. The enrichments were respectively 1.2 and 5.5. Pervaporation is dependent on pH and only the basic form of ammonia NH3 pervaporates through the membrane. Unexpectedly, the small ammonia molecule permeated very slowly. It could be due to interactions with water molecules inside the membrane that create clusters. Moreover, NH2Cl solutions, in addition to the NH3Cl+ signal, presented a strong NH4+ signal at m/z 18.034. Ammonia presence in the low-pressure zone before ionization is probable as NH4+ was detected with all the precursors used, particularly CF3+ and trimethylbenzene that presents a proton affinity higher than monochloramine. Ammonia may be formed inside the membrane due to the fact that NH2Cl is unstable and may react with the water present in the membrane. Those results highlight the need for caution when dealing with chloramines in MIMS and more generally with unstable molecules.

Failure to reactivate salient episodic information during indirect and direct tests of memory retrieval

Several fMRI and EEG studies have demonstrated that successful episodic retrieval is accompanied by the reactivation of cortical regions that were active during encoding. These findings are consistent with influential models of episodic memory that posit that conscious retrieval (recollection) relies on hippocampally-mediated cortical reinstatement. Evidence of reactivation corresponding to episodic information that is beyond conscious awareness at the time of memory retrieval, however, is limited. A recent exception is from an EEG study by Wimber, Maaβ, Staudigl, Richardson-Klavehn, and Hanslmayr et al. (2009) in which words were encoded in the context of highly salient visual flicker entrainment and then presented at retrieval in the absence of any flicker. In that study, coherent (phase-locked) neural activity was observed at the corresponding entrained frequencies during retrieval, consistent with the notion that encoding representations were reactivated. Given the important implications of unconscious reactivation to past findings and the modeling literature, the current study set out to provide a direct replication of the previous study. Additionally, an attempt was made to extend such findings to intentional retrieval by acquiring EEG while subjects were explicitly asked to make memory judgments about the flicker frequency from encoding. Throughout a comprehensive set of analyses, the current study consistently failed to demonstrate evidence for unconscious reactivation, and instead provided support that test items were indistinguishable according to their prior encoding context. The findings thus establish an important boundary condition for the involvement of cortical reinstatement in episodic memory.

Best practice guidelines for the measurement of physical activity levels in stroke survivors: a secondary analysis of an observational study.

The aim of this study was to investigate the phenomenon of activity (increased activity in response to monitor wear) and determine the minimum wear time of accelerometers when objectively measuring habitual physical activity levels of community dwelling stroke survivors. Exploratory, secondary analyses of cross-sectional data were carried out. Physical activity variables [sitting, standing and stepping time, step count, light physical activity and moderate-to-vigorous physical activity (MVPA)] were measured with two activity monitors for 7 days. Repeated-measures analysis of variance was used to assess reactivity. Minimum wear time was assessed using regression analyses and median absolute differences. Paired t-tests were used to assess differences between weekend and weekday activity levels. There was no evidence of reactivity. Minimum wear time was 3 days for all activity variables, with the exception of MVPA, for which 7 days of monitoring was required. There were no significant differences in weekend and weekday activity levels. To accurately measure activity levels of individuals with stroke, we recommend 3 days of monitoring for all activity variables, with the exception of MVPA, which requires 7 days.

Tailored approach for management of ventricular tachycardia in cardiac sarcoidosis.

Treating ventricular tachycardia (VT) in patients with cardiac sarcoidosis (CS) is challenging as patients present in different phase of the disease (inflammatory, scar, or sometimes both). A customized approach to treatment is required for better outcomes. We describe our experience in the management of VT in CS based on the phase of the disease. Patients were considered to have myocardial inflammation if there was an increased myocardial 18 fluorodeoxy glucose (FDG) uptake in PET-CT scan of the chest (n = 14). These patients were treated with antiarrhythmic drugs (AADs) and immunosuppression. Patients with scar related VT (without active inflammation) were managed with AADs and underwent radiofrequency ablation (RFA) if unresponsive to drug therapy (n = 4). Patients previously treated for CS who presented with VT and evidence of reactivation (abnormal FDG uptake) after a quiescent period of 6 months were treated with intensified immunosuppression alongside AADs (n = 3/14). Patients with myocardial inflammation responded well to immunosuppression. Patients with drug resistant VT in the scar phase responded well to RFA. Four patients in the inflammatory group had recurrence of VT during follow-up of whom 3 were found to have disease reactivation. Intensified immunosuppression suppressed VT in all 3 patients. In 1 patient, VT recurrence was found to be scar related and required RFA for control. Tailoring therapy for VT in CS according to the phase of disease results in good clinical outcome and avoids unnecessary immunosuppression.

Solution‐state NMR analysis of hydroxymethylated resorcinol cured in the presence of crude milled‐wood lignin from Acer saccharum

ABSTRACTResorcinol‐formaldehyde adhesives can reinforce stress fractures that appear from wood surface preparation. Researchers have found that applying the resorcinol‐formaldehyde prepolymer, hydroxymethylated resorcinol, to the surface of wood improves the bond strength of epoxy and polyurethane adhesives to wood. Hydroxymethylated resorcinol is thought to plasticize lignin components and stabilize stress fractures through reactions with lignin subunits and hemicelluloses in wood. In this study, a dilute solution of hydroxymethylated resorcinol (HMR) is cured in the presence of a crude milled‐wood lignin (cMWL) from Acer saccharum and subsequently dissolved in dimethylsulfoxide‐d6 to delineate reactivity with lignin and O‐acetyl‐(4‐O‐methylglucurono)xylan using solution‐state NMR spectroscopy. 1H–13C single‐bond correlation NMR experiments revealed that the HMR only formed 4,4′‐diarylmethane structures with itself in the presence of the cMWL; the 2‐methylols that formed remained free and did not crosslink with resorcinol. Cured HMR resin formed both 4,4′‐ and 2,4‐diarylmethane structures, confirming that the presence of lignin and O‐acetyl‐(4‐O‐methylglucurono)xylan hinders crosslinking at the C‐2 position. No evidence of reactivity between HMR and lignin subunits was found. New peaks consistent with ester linkages were observed in 13C‐NMR spectra of the cMWL sample treated with HMR that may be attributable to HMR moieties condensing with glucuronic acid substituents. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45398.

Ixekizumab treatment shows no evidence for reactivation of previous or latent tuberculosis infection in subjects with psoriasis: An integrated analysis of 7 clinical trials

Ixekizumab treatment shows no evidence for reactivation of previous or latent tuberculosis infection in subjects with psoriasis: An integrated analysis of 7 clinical trials

Are intensive data collection methods in pain research feasible in those with physical disability? A study in persons with chronic pain and spinal cord injury.

Intensive repeated measures data collection procedures, such as ecological momentary assessment (EMA) and end-of-day (EOD) diaries, are becoming more prominent in pain research. Existing data on the feasibility of such methods is encouraging; however, almost nothing is known about feasibility in clinical populations with significant physical disabilities. Research methodology feasibility is crucial to the inclusion of individuals with physical disability in pain research given the high prevalence and impact of pain in these populations. The aim of this study was to examine study compliance, protocol acceptability, and reactivity of intensive data collection methods in adults with chronic pain and spinal cord injury (SCI). Secondary analysis of data from a 7-day EMA and EOD diary study in a sample of 131 community dwelling adults with SCI. Results showed rates of missing data ranged from 18.4 to 22.8% across measures. Participant compliance was related to time of day/presence of audible prompts, mobility aid use, race, and baseline levels of pain and pain interference, with more missing data at wake and bedtimes/no prompts, and for those who used hand-held mobility devices, identified as black/African American, and/or reported higher baseline pain and pain interference. Participants rated the study methodology as generally highly acceptable and expressed willingness to participate in similar studies of much longer duration. There was no evidence of reactivity, defined as temporal shifts in pain or pain interference ratings. Overall, intensive pain data collection is feasible in persons with SCI with no evidence that the methodology impacts pain intensity or pain interference ratings.

Examination of Accelerometer Reactivity Among a Population Sample of Children, Adolescents, and Adults.

To examine whether accelerometer-measured physical activity-based reactivity was present in a nationally representative sample of U.S. children (6-11 yrs), adolescents (12-17 yrs), and adults (≥20 yrs). Data from the 2003-2006 National Health and Nutrition Examination Survey (N = 674, 6-85 yrs) were used. Physical activity (PA) was assessed using the ActiGraph 7164 accelerometer, with PA assessed over 7 days of monitoring. Two PA metrics were assessed, including activity counts per day (CPD) and time spent in moderate-to-vigorous PA. Evidence of reactivity was defined as a statistically significantly change in either of these 2 PA metrics from day 1 of monitoring to days 2 or 3, with day 1 of monitoring being a Monday. Suggestion of reactivity was observed only for the adult population where CPD from days 2 and 3 (297,140.6 ± 7920.3 and 295,812.9 ± 8364.9), respectively, differed significantly from day 1 (309,611.5 ± 9134.9) over the monitoring period (4.0% to 4.5% change). The analysis was conducted 2 additional times with differing start days (Tuesday and Wednesday), and this approach failed to demonstrated a reactive presence. In this national sample of U.S. children, adolescents and adults, we did not observe sufficient evidence of accelerometer reactivity.

Commentary: Episodic Memory Retrieval Functionally Relies on Very Rapid Reactivation of Sensory Information.

Commentary: Episodic Memory Retrieval Functionally Relies on Very Rapid Reactivation of Sensory Information.