Correlates of Problematic Gambling in Emerging Adult University Students in Ireland.

INTRODUCTION: Understanding the correlates of problematic gambling among emerging adult university students is crucial for developing effective approaches to minimise harm. METHODS: This cross-sectional survey study reports on 397 18-25 year old emerging adults studying at Irish universities who completed an online survey about problematic gambling and a range of biopsychosocial variables. Chi-square and binary logistic regression analyses explored the relationships between problematic gambling and the biopsychosocial variables measured. RESULTS: Chi-square analyses showed that being male, having an online gambling account, having a mobile gambling app, novelty seeking (impulsivity), harm avoidance (fear of uncertainty), and high alcohol volume consumption were significantly associated with problematic gambling. Regression analyses showed that individuals were more likely to report problematic gambling if they were male (OR = 9.57 times), had an online gambling account (OR = 17.05 times), had a mobile gambling app (OR = 20.37 times), scored high in impulsivity (OR = 7.79 times), and reported high alcohol volume consumption (OR = 4.66 times). Individuals were less likely to report problematic gambling if they scored high in fear of uncertainty (OR = 0.26 times). CONCLUSIONS: A high rate of problematic gambling was observed among the current study sample. Participants were more likely to reported problematic gambling if they were male, had online gambling accounts, mobile gambling apps, scored high in impulsivity, scored low in fear of uncertainty, or consumed high volumes of alcohol in typical drinking sessions. These findings have implications for Irish legislation and policy-makers, Irish higher education institutions, and young adult Irish university students.

The prevalence of anxiety in respiratory and sleep diseases: A systematic review and meta-analysis.

BACKGROUND: Anxiety is common in those with chronic physical health conditions and can have significant impacts on both quality of life and physical health outcomes. Despite this, there are limited studies comprehensively investigating the prevalence of anxiety in respiratory and sleep medicine settings. This systematic review and meta-analysis aims to provide insight into the global prevalence of anxiety symptoms/disorders in respiratory and sleep medicine outpatients. METHODS: PubMed, Embase, Cochrane, PsycINFO and Google Scholar databases were searched from database inception to January 23, 2023 for studies assessing the prevalence of anxiety in adult (≥16 years) respiratory and sleep medicine outpatients. Data was screened and extracted independently by two investigators. Anxiety was measured using various self-report questionnaires, structured interviews, and/or patient records. Using CMA software for the meta-analysis, a random-effects model was used for pooled estimates, and subgroup analysis was conducted on relevant models using a mixed-effects model. RESULTS: 116 studies were included, featuring 36,340 participants across 40 countries. The pooled prevalence of anxiety was 30.3 % (95%CI 27.9-32.9 %, 10,679/36,340). Subgroup analysis found a significant difference across type of condition, with pulmonary tuberculosis the highest at 43.1 % and COVID-19 outpatients the lowest at 23.4 %. No significant difference was found across anxiety types, country or age. Female sex and the use of self-report measures was associated with significantly higher anxiety estimates. CONCLUSIONS: Anxiety is a common experience amongst patients in respiratory and sleep medicine outpatient settings. Thus, it is crucial that anxiety identification and management is considered by physicians in the field. REGISTRATION: The protocol is registered in PROSPERO (CRD42021282416).

Study Protocol: Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project.

BACKGROUND: Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. METHODS: The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. CONCLUSION: Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Malonate given at reperfusion prevents post-myocardial infarction heart failure by decreasing ischemia/reperfusion injury.

The mitochondrial metabolite succinate is a key driver of ischemia/reperfusion injury (IRI). Targeting succinate metabolism by inhibiting succinate dehydrogenase (SDH) upon reperfusion using malonate is an effective therapeutic strategy to achieve cardioprotection in the short term (< 24 h reperfusion) in mouse and pig in vivo myocardial infarction (MI) models. We aimed to assess whether inhibiting IRI with malonate given upon reperfusion could prevent post-MI heart failure (HF) assessed after 28 days. Male C57BL/6 J mice were subjected to 30 min left anterior coronary artery (LAD) occlusion, before reperfusion for 28 days. Malonate or without-malonate control was infused as a single dose upon reperfusion. Cardiac function was assessed by echocardiography and fibrosis by Masson's trichrome staining. Reperfusion without malonate significantly reduced ejection fraction (~ 47%), fractional shortening (~ 23%) and elevated collagen deposition 28 days post-MI. Malonate, administered as a single infusion (16 mg/kg/min for 10 min) upon reperfusion, gave a significant cardioprotective effect, with ejection fraction (~ 60%) and fractional shortening (~ 30%) preserved and less collagen deposition. Using an acidified malonate formulation, to enhance its uptake into cardiomyocytes via the monocarboxylate transporter 1, both 1.6 and 16 mg/kg/min 10 min infusion led to robust long-term cardioprotection with preserved ejection fraction (> 60%) and fractional shortening (~ 30%), as well as significantly less collagen deposition than control hearts. Malonate administration upon reperfusion prevents post-MI HF. Acidification of malonate enables lower doses of malonate to also achieve long-term cardioprotection post-MI. Therefore, the administration of acidified malonate upon reperfusion is a promising therapeutic strategy to prevent IRI and post-MI HF.

Outcomes of Percutaneous Endoscopic Gastrostomy in Huntington's Disease at a Tertiary Center.

BACKGROUND: Clinically assisted nutrition and hydration via percutaneous endoscopic gastrostomy (PEG) is a therapeutic option to ameliorate the difficulties associated with enhanced catabolism, weight loss, and dysphagia in Huntington's disease (HD). OBJECTIVES: The objective is to provide insights into demographics, staging (Shoulson-Fahn), complications, weight trajectories, and survival rates in people with HD (pwHD) who underwent PEG. METHODS: This retrospective study included 705 consecutive pwHD who attended our HD clinic between July 2006 and March 2024, of whom 52 underwent PEG. A control group (n = 52), comprising pwHD without PEG, were closely matched for sex, stage, age, CAG length, and disease burden score at PEG. The study was registered as a service evaluation at the National Hospital for Neurology and Neurosurgery. RESULTS: PEG prevalence was 15.0% (n = 52/347) among manifest pwHD: 4.8% (n = 3/62) for Stage 3; 33.3% (n = 16/48) for stage 4; and 44.1% (n = 30/68) for stage 5. Commonest indications were dysphagia, weight loss, and inadequate oral intake. Complications included chest infection, tube dislodgement, and peristomal and skin infections. Modeling of weight trajectories after PEG found no difference between PEG and non-PEG groups. Mortality rate was 34.6% (n = 18/52) in the PEG and 36.5% (n = 19/52) in the non-PEG groups (P = 0.84). Treatment duration (until study endpoint or death) was 3.48 years (interquartile range = 1.71-6.02; range = 0.23-18.8), with 65.4% (n = 34/52) alive at the study endpoint. CONCLUSION: PEG in pwHD at-risk for weight loss may help slow weight loss. Prospective studies are required to strengthen PEG decision-making in pwHD. PEG survival was much longer than other dementias, highlighting the need to consider PEG independently in pwHD.

How do transfusion services manage patients taking therapies such as anti-CD38 and anti-CD47 known to interfere with red blood cell compatibility testing?

BACKGROUND: Drugs such as daratumumab (Darzalex, anti-CD38) and Hu5F9-G4 (magrolimab, anti-CD47) may interfere with red blood cell compatibility testing as CD38 and CD47 are expressed on red blood cells. STUDY DESIGN AND METHODS: A survey of AABB member transfusion services was undertaken to understand their experiences of managing patients taking therapeutic monoclonal antibodies that are known to interfere with blood grouping and compatibility testing. RESULTS: The survey was distributed to the contact person at US-based AABB member transfusion services. The response rate was 27%. 172 of 240 (72%) indicated they had difficulties in performing compatibility testing in patients taking daratumumab and 66 of 91 (73%) reported difficulties in performing compatibility testing in patients taking magrolimab. Actions taken to provide compatible blood for these patients included referral of all samples to a reference center, blood group pheno/genotyping the patient in advance of starting the drug, treating reagent cells with 0.2 M dithiothreitol and using K-negative red cell units for patients taking daratumumab, and Gamma-clone (Immucor) anti-IgG for indirect antiglobulin testing for patients taking magrolimab. Lack of communication from clinical services about drug treatment was identified as a concern. CONCLUSION: The results of the survey demonstrate that transfusion services are having challenges with the transfusion management of patients taking therapeutic monoclonal antibodies, and further education is needed.

Predictors of prolonged length of stay after elective carotid revascularization.

OBJECTIVE: Postoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of >1 day, after elective carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of >1 day, after each procedure. RESULTS: A total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the three procedures. Age, female sex, non-White race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday, and postoperative hypo- or hypertension were significantly associated with pLOS across all three procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (<11 cases/year), and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all three procedures; CEA (hazard ratio [HR],1.64; 95% confidence interval [CI], 1.49-1.82), TCAR (HR,1.56; 95% CI, 1.35-1.80), and TFCAS (HR, 1.33; 95%CI, 1.08-1.64) (all P < .05). CONCLUSIONS: A postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients who are risk for pLOS highlights quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

Paradoxical Psoriasis.

Cytokine blocking therapies have revolutionized the management of psoriasis and atopic dermatitis but can lead to the development of paradoxic psoriasis (PP). Patients treated with biologics should be closely monitored for the development of PP and other paradoxical eruptions (including inflammatory joint disease, inflammatory bowel disease, eczematous eruptions, lupus like eruptions, sarcoidal eruptions, and others) and occasionally the development of cutaneous T-cell lymphoma. Further understanding the immunologic mechanism of these processes will ultimately drive our understanding of and ability to predict and manage PPs.

Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Opportunities to improve feedback to reduce blood component wastage: Results of a national scheme evaluation.

BACKGROUND: Blood components are costly and scarce. The Blood Stocks Management Scheme (BSMS) was established in the United Kingdom (UK) to support hospital transfusion services and national blood services through collection, analysis, and monthly feedback of data on blood component inventory and wastage management. There is a growing evidence base on how best to deliver feedback for quality improvement. We assessed the quality and utility of the monthly BSMS component reports. METHODS: We assessed the content of BSMS reports issued in March 2023 against established criteria for effective feedback. Two researchers independently rated whether criteria spanning the five domains of goal setting, data collection, feedback content, feedback display and feedback delivery were fully, partially or not met. Disagreements were resolved through discussion. We conducted an online questionnaire survey of recipients of BSMS reports during March 2023 to assess their use of reports and seek suggestions for improvement. RESULTS: Five out of 20 criteria for effective feedback were fully met. Areas for improvement included placing more emphasis in the feedback on positive change, linking data and summary messages, and including specific suggestions for action. Respondents highlighted the value of benchmarked comparisons with other hospital transfusion services. CONCLUSION: There is scope for enhancing the effectiveness and utility of BSMS feedback reports and hence reducing wastage of blood components. This methodology for evaluation of feedback could be utilized to improve other areas of transfusion practice.

Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.

Peak alpha frequency and electroencephalographic microstates are correlated with aggression in schizophrenia.

Large scale retrospective studies have shown an association between schizophrenia and risk of violence. Overall, this increase in risk is small and does not justify or support stigmatizing public perceptions or media depictions of people with schizophrenia. Nonetheless, in some situations, some symptoms of schizophrenia can increase the risk of violent behavior. Prediction of this behavior would allow high impact preventive interventions. However, to date the neurobiological correlates of violent behavior in schizophrenia are not well understood, precluding the development of prognostic biomarkers. We used electroencephalography to measure alpha activity and microstates from 31 patients with schizophrenia and 18 age matched controls. Participants also completed multiple assessments of current aggressive tendencies and their lifetime history of aggressive acts. We found that individual alpha peak frequency was negatively correlated with aggression scores in both patients and controls (largest Spearman's r = -0.45). Furthermore, this result could be replicated in data taken from a single frontal channel suggesting that this may be possible to obtain in routine clinical settings (largest Spearman's r = -0.40). We also found that transitions between microstates corresponding to auditory and visual networks were inversely correlated with aggression scores. Finally, we found that, within patients, aggression was correlated with the degree of randomness between microstate transitions. This suggests that aggression is related to inappropriate switching between large scale brain networks and subsequent failure to appropriately integrate complicated environmental and internal stimuli. By elucidating some of the electrophysiological correlates of aggression, these data facilitate the development of prognostic biomarkers.

"We know what we should be eating, but we don't always do that." How and why people eat the way they do: a qualitative study with rural australians.

BACKGROUND: There is evidence that most people are aware of the importance of healthy eating and have a broad understanding regarding types of food that enhance or detract from health. However, greater health literacy does not always result in healthier eating. Andreasen's Social Marketing Model and Community-Based Social Marketing both posit that, in order to change health behaviours, it is crucial to understand reasons for current behaviours and perceived barriers and benefits to improved behaviours. Limited research has been conducted, however, that explores these issues with general populations. This study aimed to help address this gap in the evidence using a qualitative methodology. METHODS: Three group discussions were conducted with a total of 23 participants: (1) young women aged 18-24 with no children; (2) women aged 35-45 with primary school aged children; and (3) men aged 35-50 living with a partner and with pre- or primary school aged children. The discussions took place in a regional centre of Victoria, Australia. Transcriptions were thematically analysed using an inductive descriptive approach and with reference to a recent integrated framework of food choice that identified five key interrelated determinants: food- internal factors; food- external factors; personal-state factors; cognitive factors; and sociocultural factors. RESULTS: We found that food choice was complex, with all five determinants evident from the discussions. However, the "Social environment" sub-category of "Food-external factors", which included family, work, and social structures, and expectations (or perceived expectations) of family members, colleagues, friends, and others, was particularly prominent. Knowledge that one should practice healthy eating, which falls under the "Cognitive factor" category, while seen as an aspiration by most participants, was often viewed as unrealistic, trumped by the need and/or desire for convenience, a combination of Food-external factor: Social environment and Personal-state factor: Psychological components. CONCLUSIONS: We found that decisions regarding what, when, and how much to eat are seen as heavily influenced by factors outside the control of the individual. It appears, therefore, that a key to improving people's eating behaviours is to make it easy to eat more healthfully, or at least not much harder than eating poorly.

Measurement of lead, mercury, and cadmium in blood donors in Canada.

BACKGROUND: Fetal and neonatal exposure to lead is associated with irreversible adverse effects on neural development. There is no reliable threshold for lead effect, so limiting exposure is recommended. A significant correlation has been reported between post-transfusion blood lead level (BLL) in infants and lead levels in transfused RBC units. We measured levels of lead, mercury, and cadmium, in Canadian donor blood to investigate if concerning levels for neonatal transfusion exist. STUDY DESIGN AND METHODS: Whole blood samples from blood donors (n = 2529) were shipped cold within 7 days of donation. All permanent blood donation clinics across Canada were sampled. Twelve of these permanent clinics and 8 mobile clinics with a greater potential for having higher lead or mercury levels were oversampled. Heavy metals were measured by inductively coupled plasma mass spectrometry. RESULTS: Of all donations, 2.2% (lead) and 0.4% (mercury) had levels higher than the recommended thresholds for safe neonatal transfusion. BLLs were higher in males but there was no significant difference in the blood mercury levels of males versus females. Cadmium levels were higher in females. There was a positive correlation between donor age and levels of heavy metals, with lead having the strongest correlation (r = 0.47, p < .0001). Three clinics in close proximity to two lead-producing mines were among the clinics with the highest BLLs. Significantly higher blood mercury levels were observed in coastal clinics. CONCLUSION: Our data on donor blood heavy metal levels supports considering blood transfusion as an exposure source to heavy metals and encourages informed selection of blood units for transfusion to vulnerable groups.

Trends in Life Expectancy in Residential Long-Term Care by Sociodemographic Position in 1999-2018: A Multistate Life Table Study of Finnish Older Adults.

OBJECTIVES: Residential long-term care (LTC) use has declined in many countries over the past years. This study quantifies how changing rates of entry, exit, and mortality have contributed to trends in life expectancy in LTC (i.e., average time spent in LTC after age 65) across sociodemographic groups. METHODS: We analyzed population-register data of all Finns aged ≥65 during 1999-2018 (n = 2,016,987) with dates of LTC and death and sociodemographic characteristics. We estimated transition rates between home, LTC, and death using Poisson generalized additive models, and calculated multistate life tables across 1999-2003, 2004-2008, 2009-2013, and 2014-2018. RESULTS: Between 1999-2003 and 2004-2008, life expectancy in LTC increased from 0.75 (95% CI: 0.74-0.76) to 0.89 (95% CI: 0.88-0.90) years among men and from 1.61 (95% CI: 1.59-1.62) to 1.83 (95% CI: 1.81-1.85) years among women, mainly due to declining exit rates from LTC. Thereafter, life expectancy in LTC decreased, reaching 0.80 (95% CI: 0.79-0.81) and 1.51 (95% CI: 1.50-1.53) years among men and women, respectively, in 2014-2018. Especially among women and nonmarried men, the decline was largely due to increasing death rates in LTC. Admission rates declined throughout the study period, which offset the increase in life expectancy in LTC attributable to declining mortality in the community. Marital status differences in life expectancy in LTC narrowed over time. DISCUSSION: Recent declines in LTC use were driven by postponed LTC admission closer to death. The results suggest that across sociodemographic strata older adults enter LTC in even worse health and spend a shorter time in care than before.

A model of mitochondrial superoxide production during ischaemia-reperfusion injury for therapeutic development and mechanistic understanding.

Ischaemia-reperfusion (IR) injury is the paradoxical consequence of the rapid restoration of blood flow to an ischaemic organ. Although reperfusion is essential for tissue survival in conditions such as myocardial infarction and stroke, the excessive production of mitochondrial reactive oxygen species (ROS) upon reperfusion initiates the oxidative damage that underlies IR injury, by causing cell death and inflammation. This ROS production is caused by an accumulation of the mitochondrial metabolite succinate during ischaemia, followed by its rapid oxidation upon reperfusion by succinate dehydrogenase (SDH), driving superoxide production at complex I by reverse electron transport. Inhibitors of SDH, such as malonate, show therapeutic potential by decreasing succinate oxidation and superoxide production upon reperfusion. To better understand the mechanism of mitochondrial ROS production upon reperfusion and to assess potential therapies, we set up an in vitro model of IR injury. For this, isolated mitochondria were incubated anoxically with succinate to mimic ischaemia and then rapidly reoxygenated to replicate reperfusion, driving a burst of ROS formation. Using this system, we assess the factors that contribute to the magnitude of mitochondrial ROS production in heart, brain, and kidney mitochondria, as well as screening for inhibitors of succinate oxidation with therapeutic potential.