Can delay discounting predict vaccine hesitancy 4-years later? A study among US young adults

Despite being a major threat to health, vaccine hesitancy (i.e., refusal or reluctance to vaccinate despite vaccine availability) is on the rise. Using a longitudinal cohort of young adults (N=1260) from Los Angeles County, California we investigated the neurobehavioral mechanisms underlying COVID-19 vaccine hesitancy. Data were collected at two time points: during adolescence (12th grade;fall 2016;average age = 16.96 (±0.42)) and during young adulthood (spring 2021;average age = 21.33 (±0.49)). Main outcomes and measures were delay discounting (DD;fall 2016) and tendency to act rashly when experiencing positive and negative emotions (UPPS-P;fall 2016);self-reported vaccine hesitancy and vaccine beliefs/knowledge (spring 2021). A principal components analysis determined four COVID-19 vaccine beliefs/knowledge themes: Collective Responsibility, Confidence and Risk Calculation, Complacency, and Convenience. Significant relationships were found between themes, COVID-19 vaccine hesitancy, and DD. Collective Responsibility (β=-1.158[-1.213,-1.102]) and Convenience (β=-0.132[-0.185,-0.078]) scores were negatively associated, while Confidence and Risk Calculation (β=0.283[0.230,0.337]) and Complacency (β=0.412[0.358,0.466]) scores were positively associated with COVID-19 vaccine hesitancy. Additionally, Collective Responsibility (β=-0.060[-0.101,-0.018]) was negatively associated, and Complacency (β=-0.063[0.021,0.105]) was positively associated with DD from fall 2016. Mediation analysis revealed immediacy bias during adolescence, measured by DD, predicted vaccine hesitancy 4 years later while being mediated by two types of vaccine beliefs/knowledge: Collective Responsibility (β=0.069[0.022,0.116]) and Complacency (β=0.026[0.008,0.044]). These findings provide a further understanding of individual vaccine-related decision-making among young adults and inform public health messaging to increase vaccination acceptance.

Struggling With Recovery From Opioids: Who Is at Risk During COVID-19?

OBJECTIVES: Individuals in recovery from opioid use disorder (OUD) are vulnerable to the impacts of the COVID-19 pandemic. Recent findings suggest increased relapse risk and overdose linked to COVID-19-related stressors. We aimed to identify individual-level factors associated with COVID-19-related impacts on recovery. METHODS: This observational study (NCT04577144) enrolled 216 participants who previously partook in long-acting buprenorphine subcutaneous injection clinical trials (2015-2017) for OUD. Participants indicated how COVID-19 affected their recovery from substance use. A machine learning approach Classification and Regression Tree analysis examined the association of 28 variables with the impact of COVID-19 on recovery, including demographics, substance use, and psychosocial factors. Ten-fold cross-validation was used to minimize overfitting. RESULTS: Twenty-six percent of the sample reported that COVID-19 had made recovery somewhat or much harder. Past-month opioid use was higher among those who reported that recovery was harder compared with those who did not (51% vs 24%, respectively; P < 0.001). The final classification tree (overall accuracy, 80%) identified the Beck Depression Inventory (BDI-II) as the strongest independent risk factor associated with reporting COVID-19 impact. Individuals with a BDI-II score ≥10 had 6.45 times greater odds of negative impact (95% confidence interval, 3.29-13.30) relative to those who scored <10. Among individuals with higher BDI-II scores, less progress in managing substance use and treatment of OUD within the past 2 to 3 years were also associated with negative impacts. CONCLUSIONS: These findings underscore the importance of monitoring depressive symptoms and perceived progress in managing substance use among those in recovery from OUD, particularly during large-magnitude crises.

A MIXED-METHOD SOCIAL NETWORK ANALYSIS OF LOW-INCOME DIVERSE OLDER VOLUNTEERS

Although the health benefits of volunteering among older adults are well established in gerontology, older migrants' abilities and interests in social participation are hardly recognized. To address the gap, we collected focus groups and survey information in Russian, Khmer, Somali, Nepali, and English to understand the volunteering experiences, social networks, and feelings of loneliness among low-income diverse volunteers in the Senior Companions Program (SCP) in Columbus, Ohio (N=41). The grounded theory approach informed the qualitative analysis. Exponential Random Graph Modeling (ERGM) was utilized to identify statistically significant structural features in the volunteers' network. Five major themes emerged from the focus groups: (1) Expanding and strengthening social networks through volunteering;(2) Experiencing and coping with loneliness;(3) Experiencing and managing the social impact of COVID;(4) Exploring and loving the program;(5) Social connections outside of the program. Graphs and preliminary ERGM results demonstrate that participants tend to form homophily-based relationships with other volunteers of the same gender (β=2.45, p< 0.001) and from the same country (β=4.86, p< 0.001). However, participants tend to form friendships with people from different racial (β= -1.12, p< 0.001) and different educational backgrounds (β = -0.88, p< 0.001). The tendency to reciprocate (β= 0.96, p< 0.001) and to form triads (β= 9.90, p< 0.001) are both positively significant in the networks. Findings imply that practitioners should attend to within- and cross-cultural relationships in programs for diverse older adults. Addressing language barriers and other sources of homophily may facilitate cross-cultural friendships.

Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic. Methods: In a 3 × 2 randomized factorial design, participants (n = 23) received 900 pulses of 20 Hz rTMS to the left dorsolateral prefrontal cortex (PFC) in one of three Durations (8, 12, or 16 days of stimulation) and two Intensities (1 or 2 sessions per day). We examined direction and magnitude of the effect sizes on latency to relapse, 6-month point-prevalence abstinence rates, research burden, and delay discounting rates. Results: A large effect size was found for Duration and a medium for Intensity for latency to relapse. Increasing Duration increased the odds of abstinence 7-8-fold while increasing Intensity doubled the odds of abstinence. A large effect size was found for Duration, a small for Intensity for delay discounting rate. Increasing Duration and Intensity had a small effect on participant burden. Conclusion: Findings provide preliminary support for delay discounting as a therapeutic target and for increasing Duration and Intensity to achieve larger effect sizes for long-term smoking cessation and will provide a pre-pandemic comparison for data collected during the pandemic. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03865472].

Microrna Profiles in Saliva of Children with and Without Severe Disease Due to Severe Acute Respiratory Syndrome Corona Virus 2 Infection

Background: The majority of children with exposure to SARSCoV-2 virus have mild disease. However severe diseases such as Multisystem inflammatory syndrome (MISC) and pneumonia do occur in children. Currently, there are no established biomarkers that can predict progression to severe disease in children exposed to the virus. MicroRNAs (miRNAs) are non-coding RNAs that can be found in saliva and are thought to play a role in the regulation of inflammation following an infection. Our objective was to compare the miRNA profile in saliva of children with or without severe disease due to SARS-CoV-2 infection. Methods: This prospective observational study was supported by the National Institutes of Health (NIH) RADx Program. Children ≤ 18 years of age presenting to two tertiary care children's hospitals with symptoms of SARS-CoV-2 infection (confirmed by PCR test, serology or epidemiological link) were enrolled between 03/29/2021 and 04/30/2021. Severe infection was defined as any of the following within 30 days of testing: MISC or Kawasaki disease diagnosis, requirement for oxygen > 2L, inotropes, mechanical ventilation or ECMO, or the occurrence of death. Informed consent and a saliva swab were obtained at the time of SARS-CoV-2 diagnosis (DNA Genotek, Ottowa Canada), and RNA was extracted (Qiagen, Germantown, MD). Small RNA species (<50 base pairs) were interrogated via shotgun sequencing (HiSeq 2500, Illumina, San Diego, CA) and miRNAs were quantified through alignment to the human genome (GRCh38). RNA features with sparse counts (<10 in 90% of samples) were filtered, and the data was quantile normalized and mean-center scaled. Salivary miRNA levels were compared between those with severe and non-severe SARS-CoV-2 infection using Wilcoxon tests with Benjamini Hochberg multiple testing corrections. In addition, a logistic regression analysis was used to identify miRNA pairs that could best discriminate severe cases based on a Monte Carlo 100-fold cross-validated area under receiver operating characteristic curve (AUROC). Results: Samples from 33 children were analyzed. Median age was 3 (3, 10) years and 54.5% were males. Of the total, 29 were RT PCR positive, 4 had a positive serology and 6 children had severe infection. Seven miRNAs displayed significant differences (Fold change >2, FDR adjusted p < 0.1) among children with severe SARS-CoV-2 infection (Table). All seven miRNAs were up-regulated in severe SARS-CoV-2 cases. A logistic regression using a single ratio of miR-296-5p/miR-378j yielded 1.0 AUROC for differentiating children with severe infection (Figure). Conclusion: In this interim analysis of salivary miRNA in childhood SARS-CoV-2 infection, we found a differential expression of 7 salivary miRNAs in children with severe infection. Ongoing work will seek to validate these findings and explore the role of miRNA in predicting severe SARS-CoV-2 infection in children. Receiver operating characteristic curve and box plot displaying the complete differentiation of severe and non- severe SARSCoV-2 cases using a ratio of miR-296-5p and miR-378j levels in saliva.

Brilacidin, a Non-Peptide Defensin-Mimetic Molecule, Inhibits SARS-CoV-2 Infection by Blocking Viral Entry.

Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS-CoV-2 infection but had no effect after viral entry. Brilacidin inhibited pseudotyped SARS-CoV-2 viruses expressing spike proteins from the P.1 Brazil strain and the B.1.1.7 UK strain. Brilacidin affected viral attachment in hACE2-dependent and independent manners depending on the concentrations. The inhibitory effect on viral entry was not mediated through blocking the binding of either the spike receptor-binding domain or the spike S1 protein to hACE2 proteins. Taken together, brilacidin inhibits SARS-CoV-2 infection by blocking viral entry and is active against SARS-CoV-2 variants.

Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration

Background Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic. Methods In a 3 × 2 randomized factorial design, participants (n = 23) received 900 pulses of 20 Hz rTMS to the left dorsolateral prefrontal cortex (PFC) in one of three Durations (8, 12, or 16 days of stimulation) and two Intensities (1 or 2 sessions per day). We examined direction and magnitude of the effect sizes on latency to relapse, 6-month point-prevalence abstinence rates, research burden, and delay discounting rates. Results A large effect size was found for Duration and a medium for Intensity for latency to relapse. Increasing Duration increased the odds of abstinence 7–8-fold while increasing Intensity doubled the odds of abstinence. A large effect size was found for Duration, a small for Intensity for delay discounting rate. Increasing Duration and Intensity had a small effect on participant burden. Conclusion Findings provide preliminary support for delay discounting as a therapeutic target and for increasing Duration and Intensity to achieve larger effect sizes for long-term smoking cessation and will provide a pre-pandemic comparison for data collected during the pandemic. Clinical Trial Registration [www.ClinicalTrials.gov], identifier [NCT03865472].

Cognitive function following SARS-CoV-2 infection in a population-representative Canadian sample.

Background: SARS-CoV-2 infection is believed to adversely affect the brain, but the degree of impact on socially relevant cognitive functioning and decision-making is not well-studied, particularly among those less vulnerable to age-related mortality. The current study sought to determine whether infection status and COVID-19 symptom severity are associated with cognitive dysfunction among young and middled-aged adults in the general population, using self-reported lapses in executive control and a standardized decision-making task. Method: The survey sample comprised 1958 adults with a mean age of 37 years (SD â€‹= â€‹10.4); 60.8% were female. Participants reported SARS-CoV-2 infection history and, among those reporting a prior infection, COVID-19 symptom severity. Primary outcomes were self-reported symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated delay-discounting task. Results: Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of cognitive dysfunction symptoms (M adj  â€‹= â€‹1.89, SE â€‹= â€‹0.08, CI: 1.74, 2.04; n â€‹= â€‹175) than their non-infected counterparts (M adj  â€‹= â€‹1.63, SE â€‹= â€‹0.08, CI: 1.47,1.80; n â€‹= â€‹1599; ߠ​= â€‹0.26, p â€‹= â€‹.001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of cognitive dysfunction reported, with moderate (ߠ​= â€‹0.23, CI: 0.003-0.46) and very/extremely severe (ߠ​= â€‹0.69, CI: 0.22-1.16) COVID-19 symptoms being associated with significantly greater cognitive dysfunction. These effects remained reliable and of similar magnitude after controlling for demographics, vaccination status, mitigation behavior frequency, and geographic region, and after removal of those who had been intubated during hospitalization. Very similar-and comparatively larger-effects were found for the delay-discounting task, and when using only PCR confirmed SARS-CoV-2 cases. Conclusions: Positive SARS-CoV-2 infection history and moderate or higher COVID-19 symptom severity are associated with significant symptoms of cognitive dysfunction and amplified delay discounting among young and middle-aged adults with no history of medically induced coma.

Cognitive dysfunction following SARS-CoV-2 infection in a population-representative Canadian sample: A cross sectional study

Background Prior studies have documented reliable associations between SARS-CoV-2 infection and adverse cognitive impact, at least in older adults. The current study sought to determine whether SARS-CoV-2 infection and COVID-19 symptom severity are associated with cognitive dysfunction among young and middled-aged adults in the general population. Method The Canadian COVID-19 Experiences Project (CCEP) survey involves 1958 adults with equal representation of vaccinated and vaccine hesitant adults between the ages of 18 and 54 years. The sample comprised 1958 adults with a mean age of 37 years (SD = 10.4);60.8% were female. The primary outcome was symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated delay-discounting task. Results Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of symptoms of executive dysfunction (Madj = 1.89, SE = 0.08, CI: 1.74, 2.04;n = 175) than their non-infected counterparts (Madj = 1.63, SE = 0.08, CI: 1.47,1.80;n = 1599;β = 0.26, p = .001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of executive dysfunction, with moderate (β = 0.23, CI: 0.003–0.46) and very/extremely severe (β = 0.69, CI: 0.22–1.16) COVID-19 symptoms being associated with significantly greater dysfunction, compared to asymptomatic. These effects remained reliable and of similar magnitude after controlling for demographics, vaccination status, mitigation behavior frequency, and geographic region, and after removal of those who had been intubated during hospitalization. Very similar—and comparatively stronger—effects were found for the delay-discounting task, and when using only PCR confirmed SARS-CoV-2 cases. Conclusions Positive SARS-CoV-2 infection history and COVID-19 symptom severity are associated with executive dysfunction among young and middle-aged adults with no history of medically induced coma. These findings are evident on self-reported and task-related indicators of cognitive function.

Effects of 6-month episodic future thinking training on delay discounting, weight loss and HbA1c changes in individuals with prediabetes.

People with prediabetes are at risk for type 2 diabetes. They may discount the future delay discounting (DD), and not engage in preventive health behaviors. Episodic future thinking (EFT) can reduce DD when future scenarios are cued, but research is needed to assess long-term effects of EFT and when EFT is not cued. This study tested EFT training compared to control for people with prediabetes enrolled in a 6-month weight loss program on DD, weight, HbA1c, and physical activity. Results showed a reliable EFT effect on reducing DD in cued (p = 0.0035), and uncued DD tasks (p = 0.048), and significant overall changes in weight (p < 0.001), HbA1c (p, 0.001) and physical activity (p = 0.003), but no significant differences in these outcomes by group (p's > 0.05). Sixty-eight percent of the sample ended below the prediabetes HbA1c range. These results suggest that DD can be modified over extended periods, and the effects of EFT can be observed without EFT cues. However, these data do not suggest that changes in weight, HbA1c or physical activity were due to EFT training. The study was initiated before the COVID-19 pandemic which provided the opportunity to compare differences for people treated in-person or remotely. Analyses showed no differences in DD, weight, HBA1c or physical activity outcomes were observed between in-person and remote treatment, suggesting telehealth is a scalable approach to treating prediabetes.

Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response.

Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination.

Chronic pain and COVID-19: The association of delay discounting with perceived stress and pain severity.

The coronavirus disease pandemic of 2019 (COVID-19) is a worldwide threat to public health that has significantly affected the United States. The pandemic poses a variety of health risks including stressful disruptions in social and economic activity. Understanding the pandemic's effects on already vulnerable populations, such as individuals with chronic pain, may inform healthcare preparation for future catastrophic events. Given the association between excessive discounting of delayed rewards and chronic pain, this study examined relationships between delay discounting, pain severity, and COVID-19 perceived stress in individuals with chronic pain. Individuals reporting chronic pain (N = 180; 41% female; 86% white; 59% with a college degree) were recruited via the Amazon Mechanical Turk platform in this cross-sectional study. Measures of pain severity, delay discounting, probability discounting, and COVID-19 perceived stress were collected. Delay discounting was a significant predictor of overall pain severity (p < .02) and COVID-19 perceived stress (p < .001). Also, the magnitude of COVID-19 perceived stress fully mediated the relationship between delay discounting and overall pain severity (p = .004). Probability discounting was not a significant predictor of pain severity or COVID-19 perceived stress (p > .05). These findings highlight the importance of excessive discounting of delayed rewards as a potential determinant of pain severity as well as predictor of perceived stress related to the COVID-19 pandemic. Thus, the discounting of delayed rewards is of particular therapeutic importance for individuals with chronic pain in the context of stressful events. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin-a de novo designed synthetic small molecule that captures the biological properties of HDPs-on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.

Considerations for remote delivery of behavioral economic interventions for substance use disorder during COVID-19 and beyond.

The response to the COVID-19 crisis has created direct pressure on health care providers to deliver virtual care, and has created the opportunity to develop innovations in remote treatment for people with substance use disorders. Remote treatments provide an intervention delivery framework that capitalizes on technological innovations in remote monitoring of behaviors and can efficiently use information collected from people and their environment to provide personalized treatments as needed. Interventions informed by behavioral economic theories can help to harness the largely untapped potential of virtual care in substance use treatment. Behavioral economic treatments, such as contingency management, the substance-free activity session, and episodic future thinking, are positioned to leverage remote monitoring of substance use and to use personalized medicine frameworks to deliver remote interventions in the COVID-19 era and beyond.