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Background: Surf therapy combines physical activity with social support to provide a healing environment. Objective: This exploratory pre-to post-intervention study examined the effects of a novel surf therapy program for women who experienced abuse, trauma, and/or mental illness on emotional regulation, resilience, body acceptance, and gratitude. Methods: Twenty-seven women (ages 25 to 54; mean 36.32 + SD 7.79) participated in an 8-week Groundswell Surf Therapy Program held in four different coastal cities in California. Standardized self-report questionnaires were administered prior to and following the therapy program, including the Body Acceptance Scale, the Connor-Davidson Resilience Scale (CD-RISC), the Affective Style Questionnaire, and the Gratitude Questionnaire-Six-Item Form (GQ-6) in a pre-post study design. Data were analyzed by repeated measures analysis of variance (ANOVA). Results: Body acceptance [P < 0.001; partial Eta squared = 0.472] and resilience were increased [P = 0.005; partial Eta squared = 0.319] following the surf therapy intervention. Emotional regulation was examined according to three subscales, with the adjust [P < 0.001; partial Eta squared = 0.397] and tolerate [P < 0.001; partial Eta squared = 0.299] subscales increasing following the intervention, and the conceal subscale [P = 0.459; partial Eta squared = 0.031] remaining unchanged. Gratitude scores were unchanged [P = 0.425; partial Eta squared = 0.026]. Conclusion: A surf therapy program rooted in somatic and trauma-informed models was associated with improved resilience, emotional regulation, and body acceptance in at-risk women.
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Background: Deep dyspareunia affects 50% of people with endometriosis. The Ohnut is a set of interlocking rings that fit over the penis/insertive object. One or more rings can be used to limit insertion depth and reduce deep dyspareunia. Aim: We conducted a pilot, parallel, open-label randomized controlled trial (RCT) to investigate the feasibility of the study design and the acceptability and preliminary efficacy of the Ohnut. Method: Participants were recruited from a tertiary center for endometriosis. Eligibility criteria were surgically confirmed endometriosis, age 19-49 years, monogamous sexual relationship with a partner willing to participate in the study, and no comorbid superficial dyspareunia, anxiety, or depression. Couples were randomized into an intervention group or a waitlist control group using a 1:1 allocation ratio. All couples had sex as normal during weeks 1 to 4 (baseline period), and couples in the intervention group used the Ohnut with sex during weeks 5 to 10 (intervention period) while controls had sex as normal. Patient participants used daily diaries to record sexual activity and deep dyspareunia score (0-10) for the 10-week study. Intervention group participants completed an acceptability questionnaire at the end of the study. Outcomes: The primary outcomes were feasibility of the study and acceptability of the Ohnut. We also assessed differences in deep dyspareunia scores in the participants who used the Ohnut compared to the control participants who did not. Results: We recruited approximately 5 couples per month of active recruitment. Of 864 potentially eligible participants, we successfully contacted 44.7% (n = 386), of whom 8.0% (n = 31) consented, 64.8% (n = 250) were ineligible, and 27.2% (n = 105) declined. Thirty-one couples were randomly assigned to the intervention or control group, and 17 couples completed the study. Intervention group couples used the Ohnut for an average of 72.4% (32.7%) of sexual encounters during the intervention period. The mean acceptability index score for the Ohnut was 0.83 (0.078) among patients and 0.83 (0.049) among partners (index between 0 and 1). After controlling for baseline deep dyspareunia, there was a significant difference in the intervention period mean deep dyspareunia scores between the control and intervention group (4.69 (2.44) vs 2.46 (1.82), P = .012). Clinical Implications: We identified preliminary evidence for the acceptability and efficacy of the Ohnut among both patients and partners, suggesting that the Ohnut may be a useful stand-alone or adjuvant management tool for endometriosis-associated deep dyspareunia. Strengths and Limitations: Strengths of this study were the "real-world" use of the Ohnut and data collection from both patients and partners. Limitations of the study design included the strict eligibility criteria that affected feasibility and generalizability. Conclusion: This pilot RCT indicated that the Ohnut may be an acceptable and effective intervention to reduce endometriosis-associated deep dyspareunia. We identified opportunities to improve design for a larger RCT. Clinical Trial Registration: This clinical trial was registered with clinicaltrials.gov (#NCT04370444).
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Moyamoya disease (MMD) is a chronic, occlusive cerebrovasculopathy typified by progressive steno-occlusive disease of the intracranial internal carotid arteries (ICAs) and their proximal branches. Moyamoya syndrome (MMS) categorizes patients with characteristic MMD plus associated conditions. As such, the most usual presentations are those that occur with cerebral ischemia, specifically transient ischemic attack, acute ischemic stroke, and seizures. Hemorrhagic stroke, headaches, and migraines can also occur secondary to the compensatory growth of fragile collateral vessels propagated by chronic cerebral ischemia. While the pathophysiology of MMD is unknown, there remain numerous clinical associations including radiation therapy to the brain, inherited genetic syndromes, hematologic disorders, and autoimmune conditions. We describe the case of a 31-year-old woman who presented with recurrent ischemic cerebral infarcts secondary to rapidly progressive, bilateral MMD despite undergoing early unilateral surgical revascularization with direct arterial bypass. She had numerous metabolic conditions and rapidly decompensated, ultimately passing away despite intensive and aggressive interventions. The present case highlights that progression of moyamoya disease to bilateral involvement can occur very rapidly, within a mere 6 weeks, a phenomenon which has not been documented in the literature to our knowledge.
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The intersectional risks of children in United States immigrant communities include environmental exposures. Pesticide exposures and their biological outcomes are not well characterized in this population group. We assessed pesticide exposure and related these exposures to DNA double-strand breaks (DSBs) in Latinx children from rural, farmworker families (FW; N = 30) and from urban, non-farmworker families (NFW; N = 15) living in North Carolina. DSBs were quantified in hair follicular cells by immunostaining of 53BP1, and exposure to 72 pesticides and pesticide degradation products were determined using silicone wristbands. Cholinesterase activity was measured in blood samples. DSB frequencies were higher in FW compared to NFW children. Seasonal effects were detected in the FW group, with highest DNA damage levels in April-June and lowest levels in October-November. Acetylcholinesterase depression had the same seasonality and correlated with follicular DNA damage. Organophosphate pesticides were more frequently detected in FW than in NFW children. Participants with organophosphate detections had increased follicular DNA damage compared to participants without organophosphate detection. Follicular DNA damage did not correlate with organochlorine or pyrethroid detections and was not associated with the total number of pesticides detected in the wristbands. These results point to rural disparities in pesticide exposures and their outcomes in children from vulnerable immigrant communities. They suggest that among the different classes of pesticides, organophosphates have the strongest genotoxic effects. Assessing pesticide exposures and their consequences at the individual level is key to environmental surveillance programs. To this end, the minimally invasive combined approach used here is particularly well suited for children. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-023-00609-1.
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BACKGROUND: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD). METHODS: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients. RESULTS: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts.We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a "positive" or "negative" result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining "indeterminate" patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity. CONCLUSIONS: Agreement of total serum copper and LBC fraction classification may constitute an effective "rule-in" and "rule-out" assessment for WD-TN patients.
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Reactive capture of carbon dioxide (CO2) offers an electrified pathway to produce renewable carbon monoxide (CO), which can then be upgraded into long-chain hydrocarbons and fuels. Previous reactive capture systems relied on hydroxide- or amine-based capture solutions. However, selectivity for CO remains low (<50%) for hydroxide-based systems and conventional amines are prone to oxygen (O2) degradation. Here, we develop a reactive capture strategy using potassium glycinate (K-GLY), an amino acid salt (AAS) capture solution applicable to O2-rich CO2-lean conditions. By employing a single-atom catalyst, engineering the capture solution, and elevating the operating temperature and pressure, we increase the availability of dissolved in-situ CO2 and achieve CO production with 64% Faradaic efficiency (FE) at 50 mA cm-2. We report a measured CO energy efficiency (EE) of 31% and an energy intensity of 40 GJ tCO-1, exceeding the best hydroxide- and amine-based reactive capture reports. The feasibility of the full reactive capture process is demonstrated with both simulated flue gas and direct air input.
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There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial 'AEROBIC' (NCT04299308) enrolled 60 older adults who were cognitively healthy (n = 30) or cognitively impaired (n = 30) to characterize the acute brain responses to moderate [45-55% heart rate reserve (HRR)] and higher (65-75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG-PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG-PET standardized uptake value ratio (SUVR) differed between exercise (1.045 ± 0.082) and rest (0.985 ± 0.077) across subjects [Diff = -0.060, t(58) = 13.8, P < 0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56) = 161.99, P < 0.001] more in the higher intensity group [mean difference (MD) = 97.0 ± 50.8] than the moderate intensity group (MD = 40.3 ± 27.5; t = -5.252, P < 0.001). Change in lactate AUC and FDG-PET SUVR correlated significantly (R2 = 0.179, P < 0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted. KEY POINTS: Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease. Blood lactate levels increase following acute exercise. Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel. Acute exercise stimulates changes in brain-derived neurotrophic factor and other blood biomarkers.
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We assess the strategic alignment of attitudes and the active construction of attitude-based identity across two studies. Study one assessed the twitter response (hashtags in English) to the war in Ukraine for five months after Russia's first invasion of Ukraine 2022 (N = 8149). Results demonstrated that individuals publicly expressed hashtags similar to others close to them in the followership network, showing their support for Ukraine and condemnation of the Russian invasion in qualitatively different ways. Study two was a preregistered Prolific experiment with geographical European participants ran in September, 2022 (N = 1368). Results demonstrated that attitude interaction with ingroup members motivated interactants towards attitude alignment, and attitude alignment strengthened the identification that motivated the alignment in the first place. Results suggest that attitude expression is performative and constrained by one's group relationship with one's audience and the definition of social identity can be constrained by opinion-based identity performance.
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Studies on problematic online activities commonly focus on one type of online activity, such as social media. However, individuals often use their Smartphones for more than one online activity. This study examined four types of online activities (social networking, gaming, information acquisition, and short-form video viewing). Based on a combinatory assessment of problematic smartphone use and hours spent online, two groups were created from a larger sample (N = 642): a problematic smartphone user group (PSU; N = 230; F = 72%; Age = 24.99 ± 6.60) and a non-problematic smart phone user group (NPSU; N = 87; F = 62%; Age = 30.49 ± 10.22). As compared to the NPSU group, the PSU group engaged in more social networking, gaming, information acquisition, and short-form video seeing. The PSU group also scored higher on psychological distress, sleep disturbance, fear of missing out, metacognitions about Smartphone use (MSU), desire thinking (DT), and lower on satisfaction with life and cognitive reappraisal. Regression analyses were employed to probe correlates of each online activity among the PSU and NPSU groups. The findings are discussed in light of the metacognitive model of addictive behaviors and future directions are provided concerning the challenges of distinguishing individuals for problematic Internet-related behaviors.
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PURPOSE: The primary aim of this study was to compare patient-reported outcome measures (PROMs) at 1-year and 2-year follow-up following treatment for anterior shoulder instability. METHODS: Randomized controlled trials and prospective studies that evaluated and reported PROMs following a capsulolabral repair (with or without remplissage), bone augmentation or non-operative treatment to treat anterior shoulder instability at both 1-year and 2-year follow-up were included. PROMs were compared between 1-year and 2-year follow-up, forest plots with mean difference were created to compare baseline, 1-year and 2-year follow-up and scatterplots were created to visualize clinical improvement over time. RESULTS: Fourteen studies, comprising 923 patients, with level of evidence I and II were included. Nine PROMs, of which predominantly the Western Ontario Shoulder Instability Index (WOSI; 11 studies; 79%), were evaluated. Minimal to no statistically significant change in WOSI, Oxford Shoulder Instability Score (OSIS), American Shoulder and Elbow Surgeons (ASES), Subjective Shoulder Value (SSV), Simple Shoulder Test (SST), Disabilities of Arm, Shoulder, and Hand (DASH), Quick DASH, Single Assessment Numeric Evaluation (SANE) or Visual Analogue Scale (VAS) was observed between 1-year and 2-year follow-up. Pooling of the WOSI, OSIS, ASES and SANE demonstrated improvement from baseline to 1-year follow-up and minimal to no change between 1-year and 2-year follow-up. Scatterplots of the WOSI and ASES demonstrated the most improvement within 6 months and no clear improvement after 1-year follow-up. Recurrence rates increased with time but varied between studies. CONCLUSION: In contrast to recurrence rates which have been shown to increase with time, minimal to no statistically significant change was observed for any of the included PROMs between 1-year and 2-year follow-up. This finding questions whether it is necessary to evaluate PROMs in long term follow-up of patients following shoulder stabilization treatment. LEVEL OF EVIDENCE: Level II, systematic review of Level I - II studies.
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INTRODUCTION: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results. PATIENTS AND METHODS: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows. RESULTS: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3. DISCUSSION AND CONCLUSION: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective.
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Abundance estimation is frequently an objective of conservation and monitoring initiatives for threatened and other managed populations. While abundance estimation via capture-mark-recapture or spatially explicit capture-recapture is now common, such approaches are logistically challenging and expensive for species such as boreal caribou (Rangifer tarandus), which inhabit remote regions, are widely dispersed, and exist at low densities. Fortunately, the recently developed 'close-kin mark-recapture' (CKMR) framework, which uses the number of kin pairs obtained within a sample to generate an abundance estimate, eliminates the need for multiple sampling events. As a result, some caribou managers are interested in using this method to generate an abundance estimate from a single, non-invasive sampling event for caribou populations. We conducted a simulation study using realistic boreal caribou demographic rates and population sizes to assess how population size and the proportion of the population surveyed impact the accuracy and precision of single-survey CKMR-based abundance estimates. Our results indicated that abundance estimates were biased and highly imprecise when very small proportions of the population were sampled, regardless of the population size. However, the larger the population size, the smaller the required proportion of the population surveyed to generate both accurate and reasonably precise estimates. Additionally, we also present a case study in which we used the CKMR framework to generate annual female abundance estimates for a small caribou population in Jasper National Park, Alberta, Canada, from 2006 to 2015 and compared them to existing published capture-mark-recapture-based estimates. Both the accuracy and precision of the annual CKMR-based abundance estimates varied across years and were sensitive to the proportion of pairwise kinship comparisons which yielded a mother-offspring pair. Taken together, our study demonstrates that it is possible to generate CKMR-based abundance estimates from a single sampling event for small caribou populations, so long as a sufficient sampling intensity can be achieved.
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Three-dimensional (3D) ex vivo imaging of cleared intact brains of animal models and large human and non-human primate postmortem brain specimens is important for understanding the physiological neural network connectivity patterns and the pathological alterations underlying neuropsychiatric and neurological disorders. Light-sheet microscopy has emerged as a highly effective imaging modality for rapid high-resolution imaging of large cleared samples. However, the orthogonal arrangements of illumination and detection optics in light sheet microscopy limits the size of specimen that can be imaged. Recently developed light sheet theta microscopy (LSTM) technology addressed this by utilizing a unique arrangement of two illumination light paths oblique to the detection light path, while allowing perpendicular arrangement of the detection light path relative to the specimen surface. Here, we report development of a next-generation, fully integrated, and user-friendly LSTM system for rapid sub-cellular resolution imaging uniformly throughout a large specimen without constraining the lateral (XY) size. In addition, we provide a seamlessly integrated workflow for image acquisition, data storage, pre- and post-processing, enhancement, and quantitative analysis. We demonstrate the system performance by high-resolution 3D imaging of intact mouse brains and human brain samples, and complete data analysis including digital neuron tracing, vessel reconstruction and design-based stereological analysis in 3D. This technically enhanced and user-friendly LSTM implementation will enable rapid quantitative mapping of molecular and cellular features of interests in diverse types of very large samples.
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INTRODUCTION: Lack of knowledge of Early Intervention (EI) is a barrier to developmental delay (DD) management. We aimed to examine the feasibility of measuring pediatricians' knowledge of EI, determine the distribution of EI knowledge, and determine factors associated with increased EI knowledge. METHODS: We conducted an exploratory cross-sectional study with a convenience sample from a local American Academy of Pediatrics chapter to administer a survey with 10 multiple-choice questions regarding the EI referral process, evaluation process, eligibility criteria and fee structure. Our outcome variable was a composite score of these 10 multiple-choice questions, Total Knowledge Score (TKS). Our predictor variables included physician characteristics (i.e., years of experience, percentage of patients seen with private insurance, receipt of EI training in the last 5 years) and practice characteristics (i.e., medical home status). RESULTS: Our sample consisted of a total of 194 pediatric residents/attendings. Multivariable regression demonstrated seeing ≥ 50% patients who were privately insured, increased experience, and receiving training in the last 5 years were associated with higher TKS. DISCUSSION: We were able to quantitatively evaluate physician's knowledge of EI and demonstrated that seeing a majority of privately insured patients, having more experience, and having received formal EI training in the last 5 years were associated with higher EI knowledge. This disproportionate distribution of EI knowledge has the potential to contribute to disparities in the management of DD. This may indicate that medical institutions, where physicians see a small percent of privately insured patients, need to hire more experienced physicians, and provide routine EI training.
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While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving a panel of experts in cardiology, nursing, emergency medicine, and medical toxicology. The results demonstrate agreement about the need to consider time of ingestion and nature of the exposure (i.e. acute, acute-on-chronic, chronic) and the use of digoxin immune Fab for life-threatening exposure to decrease risk of death. While several areas of continued uncertainty were identified, this work offers formalized guidance that may help providers better manage this persistent clinical challenge.
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In the current battle against antibiotic resistance, the resilience of Gram-negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self-assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1-2.8 µg mL-1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL-1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self-assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next-generation antimicrobial agents.
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OBJECTIVES: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions. METHODS: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B. RESULTS: In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine. INTERPRETATION: Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024.
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Triple negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSCs), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets including NQO1. Here, we identified the antioxidant enzymes NQO1 and SOD1 as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24-/loCD44+/hi mesenchymal-like CSCs in TNBC. Effective targeting of these CSC states was achieved by utilizing IB-DNQ, a potent and specific NQO1-bioactivatable futile redox cycling molecule, which generated large amounts of reactive oxygen species (ROS) including superoxide and hydrogen peroxide. Furthermore, the CSC killing effect was specifically enhanced by genetic or pharmacological inhibition of SOD1, a copper-containing superoxide dismutase highly expressed in TNBC. Mechanistically, a significant portion of NQO1 resided in the mitochondrial intermembrane space, catalyzing futile redox cycling from IB-DNQ to generate high levels of mitochondrial superoxide, and SOD1 inhibition markedly potentiated this effect resulting in mitochondrial oxidative injury, cytochrome c release, and activation of the caspase 3-mediated apoptotic pathway. Treatment with IB-DNQ alone or together with SOD1 inhibition effectively suppressed tumor growth, metastasis, and tumor-initiating potential in xenograft models of TNBC expressing different levels of NQO1. This futile oxidant-generating strategy, which targets CSCs across the epithelial-mesenchymal continuum, could be a promising therapeutic approach for treating TNBC patients.