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PURPOSE: Cancer patients who smoke may experience significant stigma due both to their disease, and negative attitudes and beliefs regarding smoking. We investigated whether internalized stigma differed between currently smoking cancer patients diagnosed with lung or head and neck cancers, other smoking related cancers, and non smoking-related cancers, and whether internalized stigma was associated with psychological distress. METHODS: This cross-sectional analysis used baseline data on 293 participants enrolled in a multi-site randomized smoking cessation intervention trial of patients with recently diagnosed cancer. Internalized stigma was assessed using five Internalized Shame items from the Social Impact of Disease Scale. Smoking-related cancers included lung, head and neck, esophageal, bladder, kidney, liver, pancreatic, colorectal, anal, small intestinal, gastric, and cervical. We used multivariable linear regression to examine whether mean internalized stigma levels differed between individuals with lung and head and neck cancers, other smoking-related cancers, and non smoking-related cancers, adjusting for potential confounders. We further examined the association of internalized stigma with depression, anxiety, and perceived stress, overall and among cancer type groups. RESULTS: Thirty-nine percent of participants were diagnosed with lung or head and neck cancer, 21% with another smoking-related cancer, and 40% with a non smoking-related cancer. In multivariable-adjusted models, participants with lung or head and neck cancers (11.6, 95% confidence intervals (CI) = 10.8-12.2; p < 0.0001) or other smoking-related cancers (10.7, 95% CI = 9.8-11.7; p = 0.03) had higher mean internalized stigma scores compared to those non-smoking-related cancers (9.3, 95% CI = 8.6-10.0). We observed similar positive associations between internalized stigma and depressive symptoms, anxiety, and perceived stress among participants with smoking-related and non smoking-related cancers. CONCLUSIONS: Among smokers, those with smoking-related cancers experienced the highest levels of internalized stigma, and greater internalized stigma was associated with greater psychological distress across cancer types. Providers should assess patients for internalized and other forms of stigma, refer patients for appropriate psychosocial support services, and address stigma in smoking cessation programs.

Background To mitigate the psychological burdens of COVID-19 for frontline clinicians (FCs), we adapted an existing evidence-based resiliency program, Stress Management and Resilience Training Relaxation Response Program (SMART-3RP), for FCs. This analysis explores moderators of stress coping to determine which subgroups of FCs benefited most from SMART-3RP. Methods 102 FCs from Mass General Brigham hospitals engaged in the adapted SMART-3RP. Assessments were completed at group entry (Week 0) and completion (Week 4). The primary outcome was stress coping, and we examined 15 possible baseline moderators. We fit linear mixed effects regression models and assessed potential baseline moderators using a likelihood ratio test. We report model-based estimates and confidence intervals for each moderator-by-time interaction (i.e., differential effect), where positive/negative values indicate more/less improvement in average perceived stress coping. Results Stress coping improved from Week 0 to Week 4 (mean improvement [95% CI] = 0.9 [0.6 to 1.2]). FCs with higher anxiety (differential effect [95% CI] = 0.3 [0.1 to 0.4]), depression (0.4 [0.2 to 0.6]), and loneliness (0.4 [0.1 to 0.6]), but lower levels of mindfulness (CAMS-Rfocus: 1.0 [0.4 to 1.6]; CAMS-Raccept: 1.3 [0.7 to 2.0]) and self-compassion (0.4, [0.1 to 0.8]) at baseline experienced greater benefits in perceived stress coping from the SMART-3RP. Baseline health uncertainty along with sociodemographic and work characteristics did not moderate stress coping. Discussion Results highlight particular sub-populations of FCs that may benefit more from a stress management intervention, especially during emergency responses (e.g., COVID-19 pandemic).

COVID-19 is a rapidly spreading disease, posing a huge hazard to global health. The plasmid vaccine pTK1A-TPA-SpikeA (named COVID- eVax) encodes the severe acute respiratory syndrome coronavirus 2 S protein receptor-binding domain, developed for intramuscular injection followed by electroporation (EP). The aim of this study was to assess the systemic toxicity and local tolerance of COVID- eVax delivered intramuscularly followed by EP in Sprague Dawley (SD) rats. The animals were killed 2 days and 4 weeks after the last injection (30-day and 57-day, respectively). No mortality was observed, and no signs of toxicity were evident, including injection site reactions. A lasting and specific immune response was observed in all treated animals, confirming the relevance of the rat as a toxicological model for this vaccine. Histopathological evaluation revealed muscle fiber necrosis associated with subchronic inflammation at the injection sites (at the 30-day time point), with a clear trend for recovery at the 57-day time point, which is expected following EP, and considered a desirable effect to mount the immune response against the target antigen. In conclusion, the intramuscular EP-assisted DNA vaccine, COVID- eVax showed an excellent safety profile in SD rats under these experimental conditions and supports its further development for use in humans.

As of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.

Adolescent and young adult (AYA) siblings of individuals with autism experience unique challenges that can promote both growth and emotional maladjustment. This study explored sibling and parent reports of siblings' lived experiences and identified learning, stressors, and concerns from those experiences. 20 neurotypical (NT) AYA siblings (ages 13-24), and 21 parents were interviewed. Themes that emerged from the data analysis included: (1) learning, empathy, and compassion (2) relationship between the degree of functional impairment and the nature of the sibling relationship; (3) reluctance to share information about siblings with peers; (4) hypervigilance associated with unpredictable behavior; (5) worries and concerns about the future. These findings contribute to the existing literature on the impact and nature of neurotypical siblings' lived experience.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is highly comorbid with emotional disorders. Mindfulness meditation can improve health outcomes in people with CVD. Calm is the most popular smartphone meditation app, but the usage patterns among people with CVD have not been explored. We conducted a secondary analysis of a cross-sectional survey study among N = 1512 Calm subscribers with CVD to explore user characteristics, usage patterns, and health changes, and compare the results among those with and without co-occurring anxiety or depression. Users were primarily white (83%), female (74%), and had relatively high income (45% with > $100,000/year). Most (67%) used Calm at least 5 ×/week and started using Calm to help with sleep (69%) and stress (67%). More users with anxiety or depression, compared to CVD-only, started Calm to help with stress (71% vs. 64%) and anxiety or depression (77% vs. 37%), and used components incorporating sounds and physical movements more often (all p’s < 0.05). Most participants reported changes in sleep, stress, and physical and mental health (60–79%), though changes were more prevalent among those with anxiety or depression (p’s < 0.001). More frequent Calm use was associated with greater health changes (p’s < 0.05). Calm users with CVD use the app regularly to help with health promotion and, particularly those with anxiety or depression, perceive health changes from their Calm use. Randomized controlled trials are needed to establish the efficacy and optimal dose of Calm use for people with CVD.

Aims Tai chi exercise has been shown in a prior randomized controlled trial to improve depression symptoms and quality of life (QoL) in patients with heart failure (HF), but correlates of these improvements are not well known. The purpose of this secondary analysis was to explore whether tai chi is associated with improvements in biopsychosocial and behavioural measures and whether such improvements are correlated with improved depression and QoL. Methods and results Participants were n = 100 adults with chronic systolic HF (mean age = 67.4, SD = 12.0; 64% male; 96% White; New York Heart Association class = 1–3) randomized to a 12 week tai chi exercise intervention or health education control. Constructs of interest included social support, exercise self‐efficacy, activity engagement, sense of coherence, and inflammatory biomarkers. Tai chi was associated with increased everyday activity engagement compared with the health education group (P

Supplemental Material for Further Examination of the Psychometric Properties of the Current Experiences Scale and Model of Resiliency by James Groves, Christina Luberto, Gregory Fricchione, and Elyse Park in Global Advances in Health and Medicine

There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A(2) (sPLA(2)) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA(2) group IIA (sPLA(2)-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA(2)-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA(2)-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator–based (LASSO-based) regression analysis additionally identified sPLA(2)-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA(2)-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index–based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA(2)-IIA as a therapeutic target to reduce COVID-19 mortality.

Sphingolipids, associated enzymes, and the sphingolipid pathway are implicated in complex, multifaceted roles impacting several cell functions, such as cellular homeostasis, apoptosis, cell differentiation, and more through intrinsic and autocrine/paracrine mechanisms. Given this broad range of functions, it comes as no surprise that a large body of evidence points to important functions of sphingolipids in hematopoiesis. As the understanding of the processes that regulate hematopoiesis and of the specific characteristics that define each type of hematopoietic cells is being continuously refined, the understanding of the roles of sphingolipid metabolism in hematopoietic lineage commitment is also evolving. Recent findings indicate that sphingolipid alterations can modulate lineage commitment from stem cells all the way to megakaryocytic, erythroid, myeloid, and lymphoid cells. For instance, recent evidence points to the ability of de novo sphingolipids to regulate the stemness of hematopoietic stem cells while a substantial body of literature implicates various sphingolipids in specialized terminal differentiation, such as thrombopoiesis. This review provides a comprehensive discussion focused on the mechanisms that link sphingolipids to the commitment of hematopoietic cells to the different lineages, also highlighting yet to be resolved questions.

We developed a simple, rapid and cost-effective enzymatic-based cytometry platform to measure intracellular signaling pathway activity. Our single-cell microwell array platform quantifies protein phosphorylation using enzymatic signal amplification and exploiting Michaelis-Menten kinetics. Our method provides a two-fold increase in resolution compared to conventional flow cytometry.

Parents of children with Autism experience high levels of stress. Resiliency is the ability to cope and adapt when faced with stressful events. This randomized, waitlist controlled pilot trial examines the feasibility, acceptability, and preliminary efficacy of an adapted virtual mind–body group intervention for parents of children with ASD. The intervention was feasible and acceptable. The immediate treatment group showed no difference in distress and greater improvement in resiliency and stress reactivity/coping relative to the delayed treatment group, (M difference 5.78; p = .038 and M difference 7.78; p = .001 respectively). Findings showed promising feasibility, acceptability, and preliminary efficacy for parents of children with ASD.

Fear of cancer recurrence (FCR) is a common problem among cancer survivors and evidence- based interventions grounded in theoretical models are needed. Mindfulness-Based Cognitive Therapy (MBCT) is an evidence-based intervention for reducing health anxiety that could be useful to apply to FCR. However, there has only been one study of MBCT for FCR to date, and the theoretical rationale and practical application of MBCT for FCR has not been described. The purpose of this paper is to offer an evidence-based rationale for MBCT to treat FCR based on a health anxiety model; describe the process of adapting MBCT to target FCR; and present a case study of the adapted protocol for treating FCR in a young adult breast cancer survivor to illustrate its delivery, feasibility, acceptability, and associated changes in outcomes. Clinical implications and directions for future research are discussed.

Background Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine. Methods In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors. Results In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment. Conclusions These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments. Electronic supplementary material The online version of this article (10.1186/s13046-019-1084-4) contains supplementary material, which is available to authorized users.

There is an urgent need to identify cellular and molecular mechanisms responsible for severe COVID-19 disease accompanied by multiple organ failure and high mortality rates. Here, we performed untargeted/targeted lipidomics and focused biochemistry on 127 patient plasma samples, and showed high levels of circulating, enzymatically active secreted phospholipase A2 Group IIA (sPLA2-IIA) in severe and fatal COVID-19 disease compared with uninfected patients or mild illness. Machine learning demonstrated that sPLA2-IIA effectively stratifies severe from fatal COVID-19 disease. We further introduce a PLA-BUN index that combines sPLA2-IIA and blood urea nitrogen (BUN) threshold levels as a critical risk factor for mitochondrial dysfunction, sustained inflammatory injury and lethal COVID-19. With the availability of clinically tested inhibitors of sPLA2-IIA, our study opens the door to a precision intervention using indices discovered here to reduce COVID-19 mortality.

Background Individuals with epilepsy are up to twice as likely to be current cigarette smokers compared to those without. Moreover, one study showed current smoking is associated with an increased likelihood of seizures. However, outside of this one study, there is limited data on the presentation of specific smoking-related behaviors and cognitions in people with epilepsy, inhibiting our understanding of the severity of this behavior and our ability to formulate effective treatments for this population. Purpose The current study examined smoking-related behaviors and cognitions among smokers with epilepsy compared to smokers without epilepsy. Methods Participants were 43 smokers with (Mage = 43.4, SD = 11.6) and 43 smokers without (Mage = 45.5, SD = 8.8) epilepsy recruited from an urban, academic setting within the U.S. Separate Analyses of Covariance (ANCOVAs) were conducted to evaluate differences between smokers with and without epilepsy in terms of smoking behavior (i.e., daily smoking rate, nicotine dependence, number of quit attempts, smoking duration, age of smoking onset) and smoking-related cognitive processes (i.e., smoking motives, perceived barriers to smoking cessation, cessation motives) after controlling for race and problematic alcohol use. Results Smokers with epilepsy did not differ from smokers without epilepsy in terms of smoking rate (p = .51, ηp2 = .01), nicotine dependence (p = .12, ηp2 = .03), age of smoking onset (p = .42, ηp2 = .01), number of quit attempts (p = .43, ηp2 = .01), barriers to cessation (p = .30 to .80, ηp2 = .00 to .01), or cessation motives (p = .28 to .60, ηp2 = .00 to .02). Smokers without epilepsy reported higher levels of smoking for sensorimotor manipulation reasons (p = .03, ηp2 = .06) and longer smoking duration (p = .03, ηp2 = .06) than smokers with epilepsy. Conclusions Smokers with epilepsy do not appear to differ significantly from smokers without epilepsy in terms of smoking-related behaviors and cognitions, and may therefore benefit from current evidence-based treatments for smoking cessation that are not contraindicated for epilepsy (i.e., bupropion, varenicline).

Objectives This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres. Methods Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied. Results Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446–563; females 1027, 95% CI: 771–1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75–80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos. Conclusions Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.

Clinical Case Download : Download full-size image “Katie” is a 38-year-old married non-Hispanic white woman with a history of spontaneous coronary artery dissection (SCAD), who was referred for psychotherapy by her cardiologist for the treatment of anxiety and stress symptoms; these symptoms were negatively impacting her quality of life (QoL), relationships, and health behaviors. Prior to the SCAD, Katie was otherwise physically healthy and had no history of mental health problems, but she had high stress from her work and family life. Katie owned her own consulting company and worked long hours, leaving her overwhelmed and irritable and taking away time from her relationships with her husband, young daughter, and friends. Following the SCAD, Katie frequently worried about her health. She could not stop thinking about the possibility of having another SCAD and what it would mean for her health, her future, and her family. She reported frequent sadness at the thought of dying young and leaving her husband and young daughter. She was concerned that work stress was contributing to high blood pressure and increased her risk of another SCAD. When she was able to spend time with family and friends, Katie found herself short tempered and easily annoyed. She also began to overeat unhealthy foods when upset and stopped exercising. Katie expressed interest in psychotherapy to learn skills to reduce worries about her health, reduce work stress, and improve her relationship with her partner. Abstract Although cardiovascular disease (CVD) morbidity and mortality rates have decreased over the past 40–50 years, CVD remains the number one cause of death worldwide [1] . Traditional risk factors for CVD include physical health conditions, such as diabetes and hypertension (HTN), and health behaviors such as cigarette smoking and decreased physical activity. A large body of research now demonstrates the significant role that psychosocial factors (i.e., psychological, emotional, and social experiences) play in the development, progression, and prognosis of CVD. The strength of the effect of psychosocial factors on CVD outcomes is often similar to the strength of traditional risk factors. In some cases, the negative effects of psychosocial risk factors are particularly salient and stronger for women as compared to men. In this chapter, we first present an overview of the literature establishing psychosocial factors [anxiety, depression, stress, hostility, socioeconomic status (SES), and social integration] as contributors to CVD outcomes. We then discuss the potential mechanisms linking psychosocial factors to CVD. Lastly, we review the efficacy of pharmacotherapy and behavioral treatments for improving health outcomes in patients with or at risk for CVD. In all instances, we note sex differences when relevant.

Acute myeloid leukemia (AML) is a caricature of normal hematopoiesis driven from leukemia stem cells (LSC) that share some hematopoietic stem cell (HSC) programs including responsiveness to inflammatory signaling. Although inflammation dysregulates mature myeloid cells and influences stemness programs and lineage determination in HSCs by activating stress myelopoiesis, such roles in LSCs are poorly understood. Here, we show that S1PR3, a receptor for the bioactive lipid sphingosine-1-phosphate, is a central regulator that drives myeloid differentiation and activates inflammatory programs in both HSCs and LSCs. S1PR3-mediated inflammatory signatures varied in a continuum from primitive to mature myeloid states across cohorts of patients with AML, each with distinct phenotypic and clinical properties. S1PR3 was high in LSCs and blasts of mature myeloid samples with linkages to chemosensitivity, whereas S1PR3 activation in primitive samples promoted LSC differentiation leading to eradication. Our studies open new avenues for therapeutic target identification specific for each AML subset. Significance: S1PR3 is a novel regulator of myeloid fate in normal hematopoiesis that is heterogeneously expressed in AML. S1PR3 marks a subset of less primitive AML cases with a distinct inflammatory signature and therefore has clinical implications as both a therapeutic target and a biomarker to distinguish primitive from mature AML. See related commentary by Yang et al., p. 3. This article is highlighted in the In This Issue feature, p. 1

Relaxation sensitivity indexes the fear of relaxation-related events. The purpose of this study was to develop and provide initial validation of a self-report measure of relaxation sensitivity, the Relaxation Sensitivity Index (RSI). Three independent samples of undergraduate students (n=300 unselected, n=349 non-clinical, and n=197 clinical analogs with elevated anxiety/depression symptoms) completed self-report measures to examine the factor structure, reliability, and validity of the RSI. Results of exploratory and confirmatory factor analyses supported a three-factor structure (correlated Physical, Cognitive, and Social Concerns). The RSI demonstrated good internal consistency and construct validity as evidenced by expected correlations with measures of anxiety and depression symptoms. The RSI showed good predictive validity in terms of a history of fearful responding to relaxation. RSI scores were significantly higher in the symptomatic compared to non-clinical sample. Results suggest the RSI is a valid and reliable measure that may be useful in clinical and research settings.

New onset atrial fibrillation (AF) is observed in up to 37% of patients after esophagectomy for esophageal and esophago-gastric junction (EGJ) cancer. Little is known about risk factors for AF in this cohort of patients. Current literature describes an association between postoperative AF and other complications, notably anastomotic leaks and infective or pulmonary complications. The aim of this paper is to determine which factors relate to an increased risk of new-onset AF after esophagectomy. Methods We retrospectively analyzed a prospectively collected database in a high-volume, tertiary referral center for esophageal disease. All consecutive patients who underwent hybrid Ivor-Lewis (IL) esophagectomy for esophageal or EGJ cancer at the Upper GI surgery unit in Humanitas Research Hospital from January 2018 to august 2019 were evaluated for inclusion. Patients with a history of paroxysmal or chronic AF were excluded from the analysis. Complications were reported according to the ECCG classification. Association between variables and onset of AF was studied with univariable and multivariable logistic regression analysis. Results 89 IL cases among 125 esophagectomies were included for analysis. Overall complication rate was 29.2%. AF accounted for 9 cases (10.1%) and was the only complication in these patients. Anastomotic leak occurred in 2 patients (2.25%) both ECCG type 1, 3 developed significant pleural effusion (3.37%), 6 other infective conditions (6.7%). No postoperative deaths occurred. Significantly increased risk of AF was found in patients who underwent chemoradiotherapy(CRT) compared to those who received chemotherapy(CT) or no treatment(OR = 8.4, p = 0.02). If we compare only patients who received neoadjuvant treatment, a higher risk for CRT versus CT alone was found(OR = 5.5), with a trending significance(p = 0.08). Conclusion In this study, we did not find any association between AF and other complications. New-onset AF always presented as the only complication and it was significantly associated to neoadjuvant chemoradiotherapy. On the basis of this findings, we are designing a protocol with the aim of studying potential preventive intervention for postoperative FA after esophagectomy.

Editor's Note: Debate over the evidence supporting integrative care interventions not infrequently references the challenges funding research on natural agents and practices that are not patentable. The subject of this column goes to the mother of all such interventions, nature herself. Yet in this case, the authors report an awakening of research that affirms nature's power in health and well-being. This is the eighth commentary through JACM's column partnership with the Osher Collaborative for Integrative Medicine through which we seek to stimulate critical conversations via perspectives from the leaders of the Collaborative's seven prominent academically based integrative centers. The author team came together from three of the centers: David Victorson, PhD, at the Northwestern University Feinberg School of Medicine, Christina Luberto, PhD, at the Harvard Medical School, and Karen Koffler, MD, at the University of Miami Miller School of Medicine. While providing readers an understanding of how to examine nature as medicine, they propose a "goodness of fit" between the precepts of the integrative field and the natural world.-Editor-in-Chief, John Weeks (johnweeks-integrator.com).

COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.

Objective Parents of children with special needs such as learning and attentional disabilities (LADs) and autism spectrum disorder (ASD) are at high risk for stress-related disorders. The demands of parenting may compete with time for self-care behaviors such as physical activity, healthy eating, and adequate sleep. The objective was to describe health behaviors among this understudied population and assess the changes after a resilience intervention. Methods This was a secondary data analysis of a randomized controlled pilot virtual mind-body resilience intervention (Stress Management and Resiliency Training: A Relaxation Response Resiliency Program) trial for parents of children with LADs (n = 52) and ASD (n = 47). Parents completed self-report questionnaires about their weekly physical activity, eating behaviors, sleep duration, and fatigue before and after the 8-week intervention. Descriptive statistics and pre-post intervention effect sizes (Cohen's d) were calculated. Results Both parent groups reported suboptimal levels of health behaviors at baseline, but ASD parents reported lower health behaviors than LAD parents. LAD parents improved more on physical activity, with a higher percentage meeting recommendations at postintervention follow-up (d = 0.71) than ASD parents (d = 0.01). Eating behaviors showed small effect size improvements for both groups. Although sleep duration improved only with small or medium effect sizes for both groups, ASD parents rated their fatigue lower after the intervention (d = 0.81). Conclusion Parents of children with special needs who participated in a virtual resilience intervention demonstrated suboptimal health behaviors. There is a need for targeted interventions for health behaviors that can promote resilience in these high-stress populations.

OBJECTIVE: Fear of cancer recurrence (FCR) is a common existential concern and source of distress among adults with a cancer history. Multiple randomized controlled trials (RCTs) have examined mind-body approaches to mitigating FCR. We summarized characteristics of these trials and calculated their pooled effects on decreasing FCR. METHODS: Six electronic databases were systematically searched from inception to May 2017, using a strategy that included multiple terms for RCTs, cancer, mind-body medicine, and FCR. Data extraction and reporting followed Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled effect sizes on self-report measures of FCR were computed by using random-effects models. RESULTS: Nineteen RCTs (pooled N = 2806) were included. Most studies (53%) were published since 2015 and targeted a single cancer type (84%; mostly breast). Intervention sessions (median = 6, mode = 4) tended to last 120 minutes and occur across 1.5 months. Delivery was predominantly in-person (63%) to either groups (42%) or individuals (42%). Most interventions incorporated multiple mind-body components (53%), commonly cognitive-behavioral skills (58%), or meditative practices (53%). Small-to-medium pooled effect sizes were observed post-intervention (Hedges’ g = −0.36, 95% CI = −0.49, −0.23, P < .001) and at follow-up assessments (median = 8 months, P < .001). Potential modifiers (control group design, group/individual delivery, use of cognitive-behavioral or mindfulness skills, number of mind-body components, cancer treatment status, and number of sessions) did not reach statistical significance. CONCLUSIONS: Mind-body interventions are efficacious for reducing FCR, with small-to-medium effect sizes that persist after intervention delivery ends. Recommendations include testing effects among survivors of various cancers and exploring the optimal integration of mind-body practices for managing fundamental uncertainties and fears during cancer survivorship.

Bcr-Abl (break-point cluster region-abelson), the oncogenic trigger of chronic myelogenous leukemia (CML), has previously been shown to up-regulate the expression and activity of sphingomyelin synthase 1 (SMS1), which contributes to the proliferation of CML cells; however, the mechanism by which this increased expression of SMS1 is mediated remains unknown. In the current study, we show that Bcr-Abl enhances the expression of SMS1 via a 30-fold up-regulation of its transcription. Of most interest, the Bcr-Abl-regulated transcription of SMS1 is initiated from a novel transcription start site (TSS) that is just upstream of the open reading frame. This shift in TSS utilization generates an SMS1 mRNA with a substantially shorter 5' UTR compared with its canonical mRNA. This shorter 5' UTR imparts a 20-fold greater translational efficiency to SMS1 mRNA, which further contributes to the increase of its expression in CML cells. Therefore, our study demonstrates that Bcr-Abl increases SMS1 protein levels via 2 concerted mechanisms: up-regulation of transcription and enhanced translation as a result of the shift in TSS utilization. Remarkably, this is the first time that an oncogene-Bcr-Abl-has been demonstrated to drive such a mechanism that up-regulates the expression of a functionally important target gene, SMS1.-Moorthi, S., Burns, T. A., Yu, G.-Q., Luberto, C. Bcr-Abl regulation of sphingomyelin synthase 1 reveals a novel oncogenic-driven mechanism of protein up-regulation.

SUMMARY Cryptococcus neoformans (C. neoformans) is estimated to cause about 220,000 new cases every year in patients with AIDS, despite advances in antifungal treatments. C. neoformans possesses a remarkable ability to disseminate through an immunocompromised host, making treatment difficult. Here, we examine the mechanism of survival of C. neoformans under varying host conditions and find a role for ceramide synthase in C. neoformans virulence. This study also provides a detailed lipidomics resource for the fungal lipid research community in addition to discovering a potential target for antifungal therapy., In Brief Cryptococcus neoformans (C. neoformans) is a fungal pathogen that causes about 220,000 deaths annually in immunocompromised individuals. Munshi et al. explore fungal lipid metabolism in the context of C. neoformans pathogenicity.

Background Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. Methods The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. Results Mortality was significantly increased for ‘All Causes’ and ‘All Malignant Neoplasm (MN)’, in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. Conclusions Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies. Electronic supplementary material The online version of this article (10.1186/s12940-019-0510-6) contains supplementary material, which is available to authorized users.

ObjectivesModels based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.MethodsWe used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.ResultsRates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.ConclusionsRates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Highlights • We explored stress, distress, and smoking in a cessation trial for cancer patients. • Patients reported decreases in stress and distress over time in both study groups. • Anxiety negatively impacted smoking cessation success at 6-mo follow-up., Introduction Cancer patients who smoke report more stress and psychological distress than patients who do not smoke. It is unclear how these emotional symptoms may modify smoking behavior in cancer patients. We examined the influence of a smoking cessation intervention for cancer patients on stress and distress, and the effects of these symptoms on smoking abstinence. Methods Mixed-methods secondary analysis of data from the Smokefree Support Study, a two-site randomized controlled trial examining the efficacy of Intensive (IT; n = 153) vs. Standard Treatment (ST; n = 150) for smoking cessation in newly diagnosed cancer patients. Stress coping, perceived stress, distress, and anxiety were self-reported at baseline, 3, and 6 months. Abstinence was biochemically-confirmed at 6 months. A subset of patients (n = 72) completed qualitative exit-interviews. Results Patients were on average, 58 years old, 56% female, and smoked a median of 10 cigarettes/day. There were no significant treatment group × time interactions or main effects of treatment group on stress or distress measures (p’s > 0.05), however there were significant main effects of time suggesting symptom improvements on each measure in both study groups (p’s

Health anxiety involves persistent worry about one's physical health, despite medical reassurance. Cognitive-behavioral therapy (CBT) is currently the most widely used, evidence-based treatment for health anxiety. Mindfulness-based cognitive therapy (MBCT) is an evidence-based cognitive-behavioral treatment approach that may be useful for health anxiety due to its focus on nonjudgmental awareness and acceptance of physical and emotional events. MBCT has largely been evaluated in a group format; however, the majority of outpatient CBT providers rely also on individual treatments. No research to date has examined the utility of MBCT delivered as an individual therapy for patients with health anxiety. The purpose of the current case study is to describe the delivery, acceptability, and effects of an individually delivered mindfulness-based cognitive-behavioral intervention on health anxiety symptoms for a young woman with severe health anxiety referred to outpatient behavioral medicine by her primary care provider. The treatment was a 16-session, patient-centered intervention largely delivered using MBCT techniques, supplemented by traditional cognitive-behavioral techniques. The patient completed a validated self-report measure of health anxiety symptoms (SHAI) at the beginning of each session. The treatment was found to be acceptable, as evidenced by high treatment attendance and patient feedback. The patient reported significant cognitive, affective, and behavioral improvements, including a 67% reduction in medial visits. Health anxiety scores on the SHAI showed a 52% decrease from the first to last session, reliable change index score of 12.11, and fell below the clinical cutoff at the final session, demonstrating clinical significance. These results suggest that it is feasible to adapt MBCT for the individual treatment of health anxiety, and that controlled trials of individual MBCT are warranted.

Anxiety is common during pregnancy and associated with poorer outcomes for mother and child. Our single-arm pilot study of an eight-week Mindfulness-Based Cognitive Therapy (MBCT) intervention for pregnant women with elevated anxiety showed significant pre- to post-intervention improvements in anxiety, depression, worry, mindfulness, and self-compassion. It remains unclear whether these improvements are maintained post-partum and whether amount of formal mindfulness practice is correlated with outcomes. The current study examined whether 1) improvements in psychosocial outcomes were maintained three months postpartum; 2) women were adherent to formal practice recommendations; and 3) amount of mindfulness practice was correlated with outcomes. Twenty-three pregnant women (M(age)=33.5, SD=4.40; 75% White; 71% with Generalized Anxiety Disorder) completed home practice logs throughout the intervention, and self-report measures before and after the intervention and three months postpartum. Results indicated that previously reported post-intervention improvements in anxiety, worry, mindfulness, and self-compassion were maintained postpartum (p’s

Numerous health behaviors, including physical activity, diet, smoking, and sleep, play a major role in preventing the development and progression of cardiovascular disease (CVD). Among these behaviors, sleep may play a pivotal role, yet it has been studied somewhat less than other behaviors and there have been few well-designed sleep intervention studies targeting CVD. Furthermore, despite the fact that these behaviors are often interrelated, interventions tend to focus on changing one health behavior rather than concurrently intervening on multiple behaviors. Psychological constructs from depression to positive affect may also have a major effect on these health behaviors and ultimately on CVD. In this review, we summarize the existing literature on the impact of sleep and other cardiac health behaviors on CVD onset and prognosis. We also describe interventions that may promote these behaviors, from established interventions such as motivational interviewing and cognitive behavioral therapy, to more novel approaches focused on mindfulness and other positive psychological constructs. Finally, we outline population-health-level care management approaches for patients with psychiatric conditions (e.g., depression) that may impact cardiac health, and discuss their potential utility in improving mental health, promoting health behaviors, and reducing CVD-related risk. Much work is still needed to better understand how sleep and other health behaviors may uniquely contribute to CVD risk, and additional high-quality studies of interventions designed to modify cardiac health behaviors are required to improve cardiovascular health in individuals and the population at large.

OBJECTIVE To investigate the epidemiology and mortality in patients with biopsy-proven giant cell arteritis (GCA) in northern Italy. METHODS All patients with incident temporal-artery biopsy-positive GCA, diagnosed between 1986 and 2012 and living in the Reggio Emilia area, were identified by using a pathology register and by reviewing all histopathologic specimens. For each patient, we identified 1 comparison subject from the same geographic area, matched for age and sex. Mortality rates and specific causes of death were reported. RESULTS There were 285 incident cases of biopsy-proven GCA (210 women) during the 26-year study period. The overall age- and sex-adjusted incidence per 100,000 persons ages ≥50 years was 5.8 (95% confidence interval [95% CI] 5.1, 6.5). Incidence was significantly higher in women (7.8 [95% CI 6.7, 8.9]) than in men (3.3 [95% CI 2.6, 4.1]) (P

Many diagnostic imaging techniques—with and without ionizing radiations—such as panoramic radiography, plain radiographs, tomography, computed tomography (CT), and magnetic resonance imaging (MRI), have been proposed for the assessment of TMJ pathologies.

Mind–body interventions (MBIs) include a wide range of behavioral therapies, such as meditation, Tai Chi, yoga, and relaxation techniques. Though heterogeneous, most MBIs are multimodal and include therapeutic components, such as mindfulness, breath awareness, and physical movement. These interventions modulate key neurocognitive, psycho-emotional, and biophysical processes that may be involved in promotion of positive health behaviors and healthcare engagement. This chapter focuses on three particularly salient self-care behaviors for pulmonary patients: medication adherence, smoking cessation, and physical activity. For example, MBIs improve processes such as attention, memory, and planning behavior, as well as increase mindfulness and disease awareness, which may support medication adherence. Similarly, for smoking cessation, MBIs cultivate awareness and engage cognitive and emotional processes such as cognitive decentering and emotion regulation that may help patients notice triggers and resist cravings. Changes in mood, self-efficacy, motivation, physical function, and cardiorespiratory fitness with various MBIs may facilitate engagement in physical activity. Healthcare professionals can successfully guide patients by actively inquiring about MBI use and preferences, and by making appropriate recommendations or referrals based on patient needs, functional status, and available community resources.

One in five children have a learning and attentional disability (LAD). Parents of children with LAD are vulnerable to distress, but an evidence-based treatment has not been developed. From June 2016 to November 2017, we conducted a mixed methods study to adapt and assess the virtual delivery of a mind-body group resiliency program, the Stress Management and Resiliency Training-Relaxation Response Resiliency Program (SMART-3RP), to meet the needs of parents of children with LAD; this is an 8-session weekly group intervention. In the first phase, we conducted 4 parent focus group interviews, 2 professional focus group interviews, and 5 professional individual interviews, and 1 pilot group to adapt the SMART-3RP to target the needs of parents of children with LAD. In the second phase, we conducted a pilot wait-list controlled study to assess the feasibility, acceptability, and preliminary efficacy of a videoconferencing delivery of the adapted program. Parents were randomized to an immediate intervention group (IG) or wait-list control group (WC). Surveys were administered at baseline (time 1), end of intervention for the IG or 3 months post-baseline for the WC (time 2), and 3 months post treatment for the IG or end of intervention for the WC (time 3). Qualitative findings illustrated high levels of parental stress, with primary stressors including navigating the educational system, interactions with other parents, familial concerns, and financial and professional sacrifices. We adapted the manual to target these stressors and modified session logistics and delivery. Fifty-three parents (mean age = 46.8; 90.6% female) participated nationally in the pilot trial. 62.5% of participants completed ≥ 6/8 sessions; 81.8% reported continued daily/weekly relaxation response exercise practice. T1–T2 comparisons found that IG versus WC participants showed significant improvements in distress [VAS], ∆M = − 1.95; d = .83 and resilience [CES], ∆M = 6.38; d = .83, as well as stress coping [MOCS-A] ∆M = 8.69; d = 1.39; depression and anxiety [PHQ-4], ∆M = − 1.79; d = .71; social support [MOS-SSS], ∆M = 5.47; d = .71; and empathy [IRI], ∆M = 3.17; d = .77; improvements were sustained at the 3 month post intervention follow-up. Pilot wait-list randomized trial findings showed promising feasibility, acceptability, and preliminary efficacy for the SMART-3RP intervention adapted for parents of children with LAD. This virtually-delivered resiliency intervention improved parents’ distress, resiliency, and stress coping, which were sustained. NCT02772432.

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74–1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p

Objective: Health uncertainty among healthcare workers has yet to be examined as a contributor to the psychological toll of the COVID-19 pandemic. We aimed to (1) characterize health uncertainty levels among healthcare workers in a large, U.S. hospital system during the COVID-19 pandemic and (2) examine associations between health uncertainty and psychological outcomes.Methods: From March to June 2020, healthcare workers in a large, urban U.S. healthcare system were invited to complete an online questionnaire. Self-report measures assessed sociodemographic characteristics and job roles, health uncertainty, and emotional wellbeing variables (anxiety, depression, loneliness, self-compassion, and coping confidence). Health uncertainty (categorical and continuous scores) was compared across each variable using correlations and ANOVAs.Results: Healthcare workers (N = 440) were on average 44.5 years of age, 88.9% female, and 84.5% non-Hispanic white. Over half (52%) endorsed experiencing health uncertainty “sometimes” to “all the time”. While unrelated to sociodemographic characteristics (ps > .05), health uncertainty was highest among pharmacists and technicians, with levels significantly higher than other roles including physicians (p < .05) and mental health and spiritual counselors (p < .05). Higher health uncertainty was associated with higher anxiety (p < .001), depression (p < .001), and loneliness (p < .001), higher self-compassion (p = .02), and lower coping confidence (p < .001).Conclusions: Health uncertainty during the COVID-19 pandemic is common among healthcare workers, with higher levels related to poorer emotional wellbeing and less confidence in their coping abilities. Further research is needed to understand the relationships between healthcare workers’ health uncertainties and associated factors (i.e., job roles) and to identify whether health uncertainty may be a modifiable target for future interventions.

Objective: The COVID-19 pandemic has strained healthcare systems worldwide, placing a high psychological burden on frontline clinicians. There is an urgent need to better understand their stressors and determine if stressors differ by clinical role. The present study assessed the concerns among frontline clinicians across a large healthcare system during the COVID-19 pandemic to inform the development of tailored supportive services.Methods: From March – June 2020, frontline clinicians across the Mass General Brigham healthcare system were invited to register for an adapted mind-body resiliency group program. Clinicians completed pre- and post-program assessments asking them to report their COVID-19-related concerns. Qualitative data were analyzed in aggregate and by clinical role using content analysis to identify overarching domains.Results: Frontline clinicians’ concerns fall within seven domains: concerns for self, patients, family members, staff, existential concerns, systems-level concerns, and job-level concerns. Concerns for self and existential concerns were most commonly reported across clinical roles. Long-term care clinicians were highly concerned about patients’ wellbeing while rehabilitation therapists were highly concerned about their family members’ health. Across groups, nurse practitioners and physician assistants more often reported job-level concerns. Concerns for staff and systems level concerns were less frequently reported across clinical roles.Conclusions: Frontline clinicians share common pandemic-related concerns, but nuances exist among the concerns most frequently reported across clinical roles. Interventions that offer stress management and resiliency training may be helpful for addressing pandemic-related concerns overall. Future research should determine if tailored support services by clinical role may be warranted.

Past work suggests African American college students may be a segment of the college population at heightened risk for anxiety and depressive symptoms; however, there remains an overarching need to broaden our understanding of individual difference variables that may be related to adverse emotional states. The purpose of the present study was to test a theoretically driven interactive model of two individual difference variables (anxiety sensitivity and emotional nonacceptance) in relation to anxiety and depressive symptoms among 133 African American undergraduate students (76.7% female, Mage = 20.9, SD = 5.6; age range = 18-53 years). Results indicated that anxiety sensitivity was positively associated with anxious arousal symptoms at higher levels of emotional nonacceptance (β = 2.1), and more strongly associated with depressive symptoms among individuals endorsing low levels of emotional nonacceptance (β = 3.8). The present data provide novel evidence suggesting there is clinically relevant interplay between anxiety sensitivity and emotional nonacceptance. These findings aid in better understanding the expression of anxiety and depressive symptoms among this population and may represent transdiagnostic constructs of relevance for early intervention.

We sought to evaluate the neurophysiology of mindfulness-based cognitive therapy for children (MBCT-C) in youth with generalized, social, and/or separation anxiety disorder who were at risk for developing bipolar disorder.Nine youth (mean age: 13 ± 2 years) with a generalized, social, and/or separation anxiety disorder and a parent with bipolar disorder completed functional magnetic resonance imaging (fMRI) while performing a continuous processing task with emotional and neutral distractors (CPT-END) prior to and following 12 weeks of MBCT-C.MBCT-C was associated with increases in activation of the bilateral insula, lentiform nucleus, and thalamus, as well as the left anterior cingulate while viewing emotional stimuli during the CPT-END, and decreases in anxiety were correlated with change in activation in the bilateral insula and anterior cingulate during the viewing of emotional stimuli (p 0.05, uncorrected; p 0.005 corrected; cluster size, 37 voxels).MBCT-C treatment in anxious youth with a familial history of bipolar disorder is associated with increased activation of brain structures that subserve interoception and the processing of internal stimuli-functions that are ostensibly improved by this treatment.