Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

TRAIL signals through the ubiquitin ligase MID1 to promote pulmonary fibrosis

© 2019 The Author(s). Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has previously been demonstrated to play a pro-inflammatory role in allergic airways disease and COPD through the upregulation of the E3 ubiquitin ligase MID1 and the subsequent deactivation of protein phosphatase 2A (PP2A). Methods: Biopsies were taken from eight IPF patients presenting to the Second Affiliated Hospital of Jilin University, China between January 2013 and February 2014 with control samples obtained from resected lung cancers. Serum TRAIL, MID1 protein and PP2A activity in biopsies, and patients' lung function were measured. Wild type and TRAIL deficient Tnfsf10 -/- BALB/c mice were administered bleomycin to induce fibrosis and some groups were treated with the FTY720 analogue AAL(s) to activate PP2A. Mouse fibroblasts were treated with recombinant TRAIL and fibrotic responses were assessed. Results: TRAIL in serum and MID1 protein levels in biopsies from IPF patients were increased compared to controls. MID1 levels were inversely associated while PP2A activity levels correlated with DLco. Tnfsf10 -/- and mice treated with the PP2A activator AAL(s) were largely protected against bleomycin-induced reductions in lung function and fibrotic changes. Addition of recombinant TRAIL to mouse fibroblasts in-vitro increased collagen production which was reversed by PP2A activation with AAL(s). Conclusion: TRAIL signalling through MID1 deactivates PP2A and promotes fibrosis with corresponding lung function decline. This may provide novel therapeutic targets for IPF

Recreational Physical Activity as an Independent Predictor of Multivariable Cardiovascular Disease Risk

The role of physical activity in preventing CVD has been highlighted by Professor Jerry Morris in the 1950’s. We report outcome of a 15-year prospective study with the aim to identify whether physical activity showed cardiovascular benefit independent of common risk factors and of central obesity. Baseline data of 8662 subjects, with no previous history of heart disease, diabetes or stroke, were obtained from an age- and gender- stratified sample of adults in Australian capital cities and were linked with the National Death Index to determine the causes of death of 610 subjects who had died to 31 December 2004. The study consisted of 4175 males (age 42.3±13.1 years) and 4487 females (age 42.8±13.2 years). Fasting serum lipid levels, systolic and diastolic blood pressure and smoking habits at baseline were recorded. The Framingham Risk Scores of 15-year mortality due to CHD and CVD were calculated using established equations. Subjects were also asked if they engaged in vigorous exercise, less vigorous exercise or walk for recreation and exercise in the past 2 weeks. Subjects in the high recreational physical activity category were 0.16 (0.06–0.43; p<0.001) and 0.12 (0.03–0.48; p = 0.003) times as likely as subjects in the low category for CVD and CHD mortality respectively. After adjusting for both the Framingham Risk Score and central obesity (Waist circumference to Hip circumference Ratio), those in the high recreational physical activity group were 0.35 (0.13–0.98) times less likely compared to the low category for CVD mortality. Recreational physical activity independently predicted reduced cardiovascular mortality over fifteen years. A public health focus on increased physical activity and preventing obesity is required to reduce the risk of CVD and CHD

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Sendaway capillary NT-proBNP in pulmonary hypertension

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing. METHODS: Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata. RESULTS: 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was -7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP. CONCLUSIONS: Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.&lt;/p&gt

Occupational and leisure time physical activity in contrasting relation to ambulatory blood pressure

Background: While moderate and vigorous leisure time physical activities are well documented to decrease the risk for cardiovascular disease, several studies have demonstrated an increased risk for cardiovascular disease in workers with high occupational activity. Research on the underlying causes to the contrasting effects of occupational and leisure time physical activity on cardiovascular health is lacking. The aim of this study was to examine the relation of objective and self-report measures of occupational and leisure time physical activity with 24-h ambulatory systolic blood pressure (BP). Methods: Results for self-reported physical activity are based on observations in 182 workers (60% male, mean age 51 years), while valid objective physical activity data were available in 151 participants. The usual level of physical activity was assessed by 5 items from the Job Content Questionnaire (high physical effort, lifting heavy loads, rapid physical activity, awkward body positions and awkward positions of head or arms at work) and one item asking about the general level of physical activity during non-working time. On a regular working day, participants wore an ambulatory BP monitor and an accelerometer physical activity monitor during 24 h. Associations were examined by means of Analysis of Covariance. Results: Workers with an overall high level of self-reported occupational physical activity as well as those who reported to often lift heavy loads at work had a higher mean systolic BP at work, at home and during sleep. However, no associations were observed between objectively measured occupational physical activity and BP. In contrast, those with objectively measured high proportion of moderate and vigorous leisure time physical activity had a significantly lower mean systolic BP during daytime, while no differences were observed according to self-reported level of leisure time physical activity. Conclusions: These findings suggest that workers reporting static occupational physical activities, unlike general physically demanding tasks characterized by dynamic movements of large muscle groups, are related to a higher daily systolic BP, while high objective levels of moderate and vigorous leisure time physical activity are related to lower daytime systolic BP. Ambulatory systolic BP may be a physiological explanatory factor for the contrasting effects of occupational and leisure time physical activity