Loss of aryl hydrocarbon receptor potentiates FoxM1 signaling to enhance self-renewal of colonic stem and progenitor cells.

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses xenobiotics, diet, and gut microbial-derived metabolites, is increasingly recognized as a key regulator of intestinal biology. However, its effects on the function of colonic stem and progenitor cells remain largely unexplored. Here, we observed that inducible deletion of AhR in Lgr5+ stem cells increases the percentage of colonic stem cells and enhances organoid initiating capacity and growth of sorted stem and progenitor cells, while AhR activation has the opposite effect. Moreover, intestinal-specific AhR knockout increases basal stem cell and crypt injury-induced cell proliferation and promotes colon tumorigenesis in a preclinical colitis-associated tumor model by upregulating FoxM1 signaling. Mechanistically, AhR transcriptionally suppresses FoxM1 expression. Activation of AhR in human organoids recapitulates phenotypes observed in mice, such as reduction in the percentage of colonic stem cells, promotion of stem cell differentiation, and attenuation of FoxM1 signaling. These findings indicate that the AhR-FoxM1 axis, at least in part, mediates colonic stem/progenitor cell behavior.

Symbiosis modulates gene expression of symbionts, but not coral hosts, under thermal challenge.

Increasing ocean temperatures are causing dysbiosis between coral hosts and their symbionts. Previous work suggests that coral host gene expression responds more strongly to environmental stress compared to their intracellular symbionts; however, the causes and consequences of this phenomenon remain untested. We hypothesized that symbionts are less responsive because hosts modulate symbiont environments to buffer stress. To test this hypothesis, we leveraged the facultative symbiosis between the scleractinian coral Oculina arbuscula and its symbiont Breviolum psygmophilum to characterize gene expression responses of both symbiotic partners in and ex hospite under thermal challenges. To characterize host and in hospite symbiont responses, symbiotic and aposymbiotic O. arbuscula were exposed to three treatments: (1) control (18°C), (2) heat (32°C), and (3) cold (6°C). This experiment was replicated with B. psygmophilum cultured from O. arbuscula to characterize ex hospite symbiont responses. Both thermal challenges elicited classic environmental stress responses (ESRs) in O. arbuscula regardless of symbiotic state, with hosts responding more strongly to cold challenge. Hosts also exhibited stronger responses than in hospite symbionts. In and ex hospite B. psygmophilum both down-regulated gene ontology pathways associated with photosynthesis under thermal challenge; however, ex hospite symbionts exhibited greater gene expression plasticity and differential expression of genes associated with ESRs. Taken together, these findings suggest that O. arbuscula hosts may buffer environments of B. psygmophilum symbionts; however, we outline the future work needed to confirm this hypothesis.

Promoting inclusive metrics of success and impact to dismantle a discriminatory reward system in science.

Success and impact metrics in science are based on a system that perpetuates sexist and racist "rewards" by prioritizing citations and impact factors. These metrics are flawed and biased against already marginalized groups and fail to accurately capture the breadth of individuals' meaningful scientific impacts. We advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion. We outline pathways for a paradigm shift in scientific values based on multidimensional mentorship and promoting mentee well-being. These actions will require collective efforts supported by academic leaders and administrators to drive essential systemic change.

AdipoRon Attenuates Wnt Signaling by Reducing Cholesterol-Dependent Plasma Membrane Rigidity.

The increasing prevalence of adult and adolescent obesity and its associated risk of colorectal cancer reinforces the urgent need to elucidate the underlying mechanisms contributing to the promotion of colon cancer in obese individuals. Adiponectin is an adipose tissue-derived adipokine, whose levels are reduced during obesity. Both epidemiological and preclinical data indicate that adiponectin suppresses colon tumorigenesis. We have previously demonstrated that both adiponectin and AdipoRon, a small-molecule adiponectin receptor agonist, suppress colon cancer risk in part by reducing the number of Lgr5+ stem cells in mouse colonic organoids. However, the mechanism by which the adiponectin signaling pathway attenuates colon cancer risk remains to be addressed. Here, we have hypothesized that adiponectin signaling supports colonic stem cell maintenance through modulation of the biophysical properties of the plasma membrane (PM). Specifically, we investigated the effects of adiponectin receptor activation by AdipoRon on the biophysical perturbations linked to the attenuation of Wnt-driven signaling and cell proliferation as determined by LEF luciferase reporter assay and colonic organoid proliferation, respectively. Using physicochemical sensitive dyes, Di-4-ANEPPDHQ and C-laurdan, we demonstrated that AdipoRon decreased the rigidity of the colonic cell PM. The decrease in membrane rigidity was associated with a reduction in PM free cholesterol levels and the intracellular accumulation of free cholesterol in lysosomes. These results suggest that adiponectin signaling plays a role in modulating cellular cholesterol homeostasis, PM biophysical properties, and Wnt-driven signaling. These findings are noteworthy because they may in part explain how obesity drives colon cancer progression.

Quality of Life following Allogeneic Stem Cell Transplantation for Patients Age >60 Years with Acute Myelogenous Leukemia.

This study of patients with acute myelogenous leukemia (AML) age ≥60 years analyzed the association between patients' performance indices-Hematopoietic Stem Cell Transplantation Comorbidity Index (HCT-CI), Karnofsky Performance Score (KPS), and European Society for Blood and Marrow Transplantation (EBMT) risk score-before undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and quality of life (QoL), quantified using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), in the first year after allo-HSCT. Over a period of 7 years, 48 evaluable patients underwent reduced-intensity conditioning allo-HSCT. The median patient age was 65 years (range, 60 to 74 years), with 2-year and 5-year overall survival (OS) of 65.8% and 52.3%, respectively. A significant improvement across all QoL scores was observed over the 12 months post-HSCT. An HCT-CI of 0 was associated with improved general QoL (FACT-G) score at 6 months compared with patients with an HCT-CI of 1 to 2 (P= .032). At 12 months post-HSCT, a pretransplantation HCT-CI ≥3 was correlated with lower QoL scores across the domains (symptom-related QoL [FACT-TOI], P= .036; FACT-G, P= .05; BMT-related QoL [FACT-BMT], P= .036). A pretransplantation KPS score of 100 versus 80 to 90 was predictive of improved QoL at 6 months post-HSCT (FACT-TOI, P = .009; FACT-G, P= .001; FACT-BMT, P= .002) but not at 1 year post-HSCT. We demonstrate that KPS and HCT-CI can predict QoL in the early post-transplantation period, with a favorable overall survival in a selected cohort of AML patients age ≥60 years.

Symbiont community diversity is more variable in corals that respond poorly to stress.

Coral reefs are declining globally as climate change and local water quality press environmental conditions beyond the physiological tolerances of holobionts-the collective of the host and its microbial symbionts. To assess the relationship between symbiont composition and holobiont stress tolerance, community diversity metrics were quantified for dinoflagellate endosymbionts (Family: Symbiodiniaceae) from eight Acropora millepora genets that thrived under or responded poorly to various stressors. These eight selected genets represent the upper and lower tails of the response distribution of 40 coral genets that were exposed to four stress treatments (and control conditions) in a 10-day experiment. Specifically, four 'best performer' coral genets were analyzed at the end of the experiment because they survived high temperature, high pCO2 , bacterial exposure, or combined stressors, whereas four 'worst performer' genets were characterized because they experienced substantial mortality under these stressors. At the end of the experiment, seven of eight coral genets mainly hosted Cladocopium symbionts, whereas the eighth genet was dominated by both Cladocopium and Durusdinium symbionts. Symbiodiniaceae alpha and beta diversity were higher in worst performing genets than in best performing genets. Symbiont communities in worst performers also differed more after stress exposure relative to their controls (based on normalized proportional differences in beta diversity), than did best performers. A generalized joint attribute model estimated the influence of host genet and treatment on Symbiodiniaceae community composition and identified strong associations among particular symbionts and host genet performance, as well as weaker associations with treatment. Although dominant symbiont physiology and function contribute to host performance, these findings emphasize the importance of symbiont community diversity and stochasticity as components of host performance. Our findings also suggest that symbiont community diversity metrics may function as indicators of resilience and have potential applications in diverse disciplines from climate change adaptation to agriculture and medicine.

Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents.

The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.

Positive genetic associations among fitness traits support evolvability of a reef-building coral under multiple stressors.

Climate change threatens organisms in a variety of interactive ways that requires simultaneous adaptation of multiple traits. Predicting evolutionary responses requires an understanding of the potential for interactions among stressors and the genetic variance and covariance among fitness-related traits that may reinforce or constrain an adaptive response. Here we investigate the capacity of Acropora millepora, a reef-building coral, to adapt to multiple environmental stressors: rising sea surface temperature, ocean acidification, and increased prevalence of infectious diseases. We measured growth rates (weight gain), coral color (a proxy for Symbiodiniaceae density), and survival, in addition to nine physiological indicators of coral and algal health in 40 coral genets exposed to each of these three stressors singly and combined. Individual stressors resulted in predicted responses (e.g., corals developed lesions after bacterial challenge and bleached under thermal stress). However, corals did not suffer substantially more when all three stressors were combined. Nor were trade-offs observed between tolerances to different stressors; instead, individuals performing well under one stressor also tended to perform well under every other stressor. An analysis of genetic correlations between traits revealed positive covariances, suggesting that selection to multiple stressors will reinforce rather than constrain the simultaneous evolution of traits related to holobiont health (e.g., weight gain and algal density). These findings support the potential for rapid coral adaptation under climate change and emphasize the importance of accounting for corals' adaptive capacity when predicting the future of coral reefs.

Resilience to oxidative and nitrosative stress is mediated by the stressosome, RsbP and SigB in Bacillus subtilis.

A bacterium's ability to thrive in the presence of multiple environmental stressors simultaneously determines its resilience. We showed that activation of the SigB-controlled general stress response by mild environmental or energy stress provided significant cross-protection to subsequent lethal oxidative, disulfide and nitrosative stress in Bacillus subtilis. SigB activation is mediated via the stressosome and RsbP, the main conduits of environmental and energy stress, respectively. Cells exposed to mild environmental stress while lacking the major stressosome components RsbT or RsbRA were highly sensitive to subsequent oxidative stress, whereas rsbRB, rsbRC, rsbRD, and ytvA null mutants showed a spectrum of sensitivity, confirming their redundant roles and suggesting they could modulate the signals generated by environmental or oxidative stress. By contrast, cells encountering stationary phase stress required RsbP but not RsbT to survive subsequent oxidative stress. Interestingly, optimum cross-protection against nitrosative stress caused by sodium nitropruside required SigB but not the known regulators, RsbT and RsbP, suggesting an additional and as yet uncharacterized route of SigB activation independent of the known regulators. Together, these results provide mechanistic information on how B. subtilis promotes enhanced resistance against lethal oxidative stress during mild environmental and energy stress conditions.

Stepping to an Auditory Metronome Improves Weight-Bearing Symmetry in Poststroke Hemiparesis.

Asymmetry in weight-bearing is a common feature in poststroke hemiparesis and is related to temporal asymmetry during walking. The aim of this study was to investigate the effect of an auditory cue for stepping in place on measures of temporal and weight-bearing asymmetry. A total of 10 community-dwelling adults (6 males and 4 females) with chronic poststroke hemiparesis performed 5 un-cued stepping trials and 5 stepping trials cued by an auditory metronome cue. A Vicon system was used to collect full body kinematic trajectories. Two force platforms were used to measure ground reaction forces. Step, swing, and stance times were used to calculate temporal symmetry ratios. Weight-bearing was assessed using the vertical component of the ground reaction force and center of mass-center of pressure separation at mid-stance. Weight-bearing asymmetry was significantly reduced during stepping with an auditory cue. Asymmetry values for step, swing, and stance times were also significantly reduced with auditory cueing. These findings show that auditory cueing when stepping in place produces immediate reductions in measures of temporal asymmetry and dynamic weight-bearing asymmetry.

Enhancing women's health: A call for social work research.

This article presents a critical synthesis of the social work empirical literature on women's health. In light of recent policy changes that directly affect women's health and social work, the authors conducted a literature review of recent publications (2010-2015) regarding social work and women's health nationally. Despite frequent accounts cited in the literature, there has been no comprehensive review of issues involving women's health and social work in the United States. The purpose of this review is to examine the current social work literature addressing women's health at the national (U.S.) level. This research presents a summary description of the status of the social work literature dealing with women's health, specifically 51 articles published between 2010 and 2015. Our search highlights the need for social work research to fill gaps and more fully address the needs of women across the lifespan.

Gene expression associated with white syndromes in a reef building coral, Acropora hyacinthus.

BACKGROUND: Corals are capable of launching diverse immune defenses at the site of direct contact with pathogens, but the molecular mechanisms of this activity and the colony-wide effects of such stressors remain poorly understood. Here we compared gene expression profiles in eight healthy Acropora hyacinthus colonies against eight colonies exhibiting tissue loss commonly associated with white syndromes, all collected from a natural reef environment near Palau. Two types of tissues were sampled from diseased corals: visibly affected and apparently healthy. RESULTS: Tag-based RNA-Seq followed by weighted gene co-expression network analysis identified groups of co-regulated differentially expressed genes between all health states (disease lesion, apparently healthy tissues of diseased colonies, and fully healthy). Differences between healthy and diseased tissues indicate activation of several innate immunity and tissue repair pathways accompanied by reduced calcification and the switch towards metabolic reliance on stored lipids. Unaffected parts of diseased colonies, although displaying a trend towards these changes, were not significantly different from fully healthy samples. Still, network analysis identified a group of genes, suggestive of altered immunity state, that were specifically up-regulated in unaffected parts of diseased colonies. CONCLUSIONS: Similarity of fully healthy samples to apparently healthy parts of diseased colonies indicates that systemic effects of white syndromes on A. hyacinthus are weak, which implies that the coral colony is largely able to sustain its physiological performance despite disease. The genes specifically up-regulated in unaffected parts of diseased colonies, instead of being the consequence of disease, might be related to the originally higher susceptibility of these colonies to naturally occurring white syndromes.

Lack of EC-SOD worsens alveolar and vascular development in a neonatal mouse model of bleomycin-induced bronchopulmonary dysplasia and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) worsens clinical outcomes in former preterm infants with bronchopulmonary dysplasia (BPD). Oxidant stress disrupts alveolar and vascular development in models of BPD. Bleomycin causes oxidative stress and induces BPD and PAH in neonatal rats. Disruption in the vascular endothelial growth factor (VEGF) and nitric oxide signaling pathways contributes to BPD. We hypothesized that loss of EC-SOD would worsen PAH associated with BPD in a neonatal mouse model of bleomycin-induced BPD by disrupting the VEGF/NO signaling pathway. METHODS: Neonatal wild-type mice (WT), and mice lacking EC-SOD (EC-SOD KO) received intraperitoneal bleomycin (2 units/kg) or phosphate-buffered saline (PBS) three times weekly and were evaluated at weeks 3 or 4. RESULTS: Lack of EC-SOD impaired alveolar development and resulted in PH (elevated right ventricular systolic pressures, right ventricular hypertrophy (RVH)), decreased vessel density, and increased small vessel muscularization. Exposure to bleomycin further impaired alveolar development, worsened RVH and vascular remodeling. Lack of EC-SOD and bleomycin treatment decreased lung total and phosphorylated VEGFR2 and eNOS protein expression. CONCLUSION: EC-SOD is critical in preserving normal lung development and loss of EC-SOD results in disrupted alveolar development, PAH and vascular remodeling at baseline, which is further worsened with bleomycin and associated with decreased activation of VEGFR2.

Intersection of coral molecular responses to a localized mortality event and ex situ deoxygenation.

In July 2016, East Bank of Flower Garden Banks (FGB) National Marine Sanctuary experienced a localized mortality event (LME) of multiple invertebrate species that ultimately led to reductions in coral cover. Abiotic data taken directly after the event suggested that acute deoxygenation contributed to the mortality. Despite the large impact of this event on the coral community, there was no direct evidence that this LME was driven by acute deoxygenation, and thus we explored whether gene expression responses of corals to the LME would indicate what abiotic factors may have contributed to the LME. Gene expression of affected and unaffected corals sampled during the mortality event revealed evidence of the physiological consequences of the LME on coral hosts and their algal symbionts from two congeneric species (Orbicella franksi and Orbicella faveolata). Affected colonies of both species differentially regulated genes involved in mitochondrial regulation and oxidative stress. To further test the hypothesis that deoxygenation led to the LME, we measured coral host and algal symbiont gene expression in response to ex situ experimental deoxygenation (control = 6.9 ± 0.08 mg L-1, anoxic = 0.083 ± 0.017 mg L-1) in healthy O. faveolata colonies from the FGB. However, this deoxygenation experiment revealed divergent gene expression patterns compared to the corals sampled during the LME and was more similar to a generalized coral environmental stress response. It is therefore likely that while the LME was connected to low oxygen, it was a series of interconnected stressors that elicited the unique gene expression responses observed here. These in situ and ex situ data highlight how field responses to stressors are unique from those in controlled laboratory conditions, and that the complexities of deoxygenation events in the field likely arise from interactions between multiple environmental factors simultaneously.

Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor.

An additional class of endogenous lipid amides, N-arachidonoyl amino acids (Ara-AAs), is growing in significance in the field of endocannabinoids. The development, validation, and application of a sensitive and selective method to simultaneously monitor and quantify the level of Ara-AAs along with anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in mouse brain has been established. The linearity of the method over the concentration ranges of 0.2-120 pg/µl for the standards of N-arachidonoyl amino acids, N-arachidonoyl alanine (NAAla), serine (NASer), γ-aminobutyric acid (NAGABA), and glycine (NAGly); 0.7-90 pg/µl for AEA-d(0)/d(8); and 7.5-950 pg/µl for 2-AG was determined with R(2) values of 0.99. Also the effects of the FAAH inhibitor URB 597 on the endogenous levels of these analytes were investigated. AEA and NASer brain levels exhibit a dose-dependent increase after systemic administration of URB 597, whereas NAGly and NAGABA were significantly decreased after treatment. NAAla and 2-AG were not altered after URB 597 treatment. The potential benefit of establishing this assay extends beyond the quantification of the Ara-AAs along with AEA and 2-AG in mouse brain, to reveal a variety of pharmacological effects and physiological roles of these analytes.

Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic ß-catenin.

Although the role of the Wnt pathway in colon carcinogenesis has been described previously, it has been recently demonstrated that Wnt signaling originates from highly dynamic nano-assemblies at the plasma membrane. However, little is known regarding the role of oncogenic APC in reshaping Wnt nanodomains. This is noteworthy, because oncogenic APC does not act autonomously and requires activation of Wnt effectors upstream of APC to drive aberrant Wnt signaling. Here, we demonstrate the role of oncogenic APC in increasing plasma membrane free cholesterol and rigidity, thereby modulating Wnt signaling hubs. This results in an overactivation of Wnt signaling in the colon. Finally, using the Drosophila sterol auxotroph model, we demonstrate the unique ability of exogenous free cholesterol to disrupt plasma membrane homeostasis and drive Wnt signaling in a wildtype APC background. Collectively, these findings provide a link between oncogenic APC, loss of plasma membrane homeostasis and CRC development.

Mechanisms and potential immune tradeoffs of accelerated coral growth induced by microfragmentation.

Microfragmentation is the act of cutting corals into small pieces (~1 cm2) to accelerate the growth rates of corals relative to growth rates observed when maintaining larger-sized fragments. This rapid tissue and skeletal expansion technique offers great potential for supporting reef restoration, yet the biological processes and tradeoffs involved in microfragmentation-mediated accelerated growth are not well understood. Here we compared growth rates across a range of successively smaller fragment sizes in multiple genets of reef-building corals, Orbicella faveolata and Montastraea cavernosa. Our results confirm prior findings that smaller initial sizes confer accelerated growth after four months of recovery in a raceway. O. faveolata transcript levels associated with growth rate include genes encoding carbonic anhydrase and glutamic acid-rich proteins, which have been previously implicated in coral biomineralization, as well as a number of unannotated transcripts that warrant further characterization. Innate immunity enzyme activity assays and gene expression results suggest a potential tradeoff between growth rate after microfragmentation and immune investment. Microfragmentation-based restoration practices have had great success on Caribbean reefs, despite widespread mortality among wild corals due to infectious diseases. Future studies should continue to examine potential immune tradeoffs throughout the microfragmentation recovery period that may affect growout survival and disease transmission after outplanting.

Fragile X syndrome in a girl with variant Turner syndrome and an isodicentric X chromosome.

Fragile X (FXS) and Turner (TS) syndromes are X-chromosome-associated disorders. Herein, we report the case of a girl in middle childhood with bicuspid aortic valve in infancy, growth failure, global developmental delay (GDD), visual problems, and coexisting attention-deficit/hyperactivity and anxiety disorders. A high-resolution karyotype in 20 cells revealed 46,X,Idic(X)(p11.21)[19]/45,X[1], suggestive of variant TS. Given her atypical phenotype, subsequent DNA testing was performed. Four FMR1 cytosine-guanine-guanine repeats (30, 410, 580 and 800) were identified, confirming the additional FXS diagnosis. This case study highlights the importance of additional genetic testing in individuals with atypical variant TS, such as unexplained GDD and distinct facial characteristics. The additional FXS diagnosis prompted new therapeutic development for the patient to advance precision healthcare.

Mixed methods evaluation of the 'real-world' implementation of group-based behavioral stop smoking support through Facebook.

INTRODUCTION: While promising evidence from trials of social-media-based stop smoking support informs service-planning, there is a need for more prospective, observational studies of smoking cessation interventions to build 'real-world' evidence. Specifically, user experiences have been under-explored with qualitative methods to date. This mixed-method evaluation of a closed Facebook group-based behavioral stop smoking support program, which was conducted in Ireland in 2018, aimed to address these issues. METHODS: Pre- and post-program surveys measured smoking abstinence (self-reported 7-day point prevalence), changes in smoking attitudes and behavior, and participant experiences. Engagement with Facebook was measured through counting 'likes' and comments, and was used to categorize groups as 'more active' and 'less active' over a 12-week period of support. Thematic content analysis of semi-structured participant interviews explored program experience in depth. RESULTS: In total, 13 of 52 participants reported smoking abstinence post-program (25.0%, 95% CI: 14.0-39.0). Participant engagement with Facebook was variable and decreased over the program. Membership of a 'more active' group was associated with better reported participant experience (e.g. 90.9% agreeing 'Facebook group helped me to quit or reduce smoking', versus 33.3% in the 'less active' group, p<0.05). Qualitative analysis identified three over-arching themes: importance of social interactions; perception of health information; and appeal of online support. CONCLUSIONS: Facebook can be used to deliver group-based behavioral stop smoking support in the real world. In Ireland, the one-month post-program abstinence outcomes achieved by other stop smoking services is approximately 50%, and while the outcomes for this service was lower (25%), it is still better than outcomes estimated for unassisted quitting. Engagement and peer-to-peer interactivity should be maximized to support positive participant experience.

Longitudinal assessment of quality of life in indolent non-Hodgkin lymphomas managed with active surveillance.

There are limited data describing the impact of active surveillance on longitudinal health-related quality of life (HRQoL) in patients with indolent non-Hodgkin lymphomas (NHL). A cohort of untreated indolent NHL patients completed FACT-LYM questionnaires at 6, 12, 18, 24, and 36 months after diagnosis. Longitudinal FACT-LYM scores were analyzed by ANOVA and generalized linear mixed models. Indolent NHL scores were compared to norm general population scores. A total of 52 patients were identified, of which 46 (88%) remained on active surveillance at 36 months. There was no significant change in any of the FACT-LYM scores over 36 months. As compared to the general population, indolent NHL patients had higher, clinically meaningful scores in physical, functional, and social well-being, but not emotional well-being. Patients with indolent NHL on active surveillance have globally preserved HRQoL for up to 3 years after diagnosis. Emotional well-being continues to be an unmet need during active surveillance.