Correlation of thermal burn hepatic dysfunction with outcomes.

INTRODUCTION: Organ dysfunction and failure increase the morbidity and mortality following major burn. Alteration of liver morphology and function is common following major burns; however, it has not received much attention. In this study we have assessed the impact of thermal burn on liver in relation with mortality. MATERIAL AND METHODS: 55 patients (33 female and 22 males) with TBSA 10-90% and age ranged from 18 to 75 years were included. A bed side serial ultrasonography to assess the volume of liver and liver function tests was done on the 2nd, 9th and 16th day following burn. Baseline demographic and clinical information such as age, gender, burn size and outcome of patient were also collected. RESULTS -: 8 patients died during 2nd week following burn and 47 survived. The mean TBSA for survivors was 37% and for non survivors 80%. Mean liver volume in survivors steadily decreased from 1693.70 cm3 to 1631.31 cm3 over 3 weeks. Mean liver volume in non- survivors steadily increased from 1855.88 cm3 to 2028.50 cm3 over 2 weeks. Liver function test in survivors steadily improved while in non survivors it deteriorated over 2 weeks. CONCLUSION: There is a correlation between altered liver morphology and function with mortality among severely burnt patients however liver volume did not show statistical significance. A decreasing trend of liver dysfunction parameters and hepatomegaly following burn is associated with good prognosis.

Giant Nabothian Cyst Mimicking a Huge Cervical Fibroid: Challenging Aspects in Laparoscopic Hysterectomy.

Nabothian cysts (NCs) are benign cervical mucous retention cysts, which are usually considered insignificant. A 45 years para 2, presented with lower abdominal heaviness, abnormal uterine bleeding and severe dysmenorrhea for 1 year. On examination, only a part of the anterior cervical lip was visible, and a tense bulging cyst was replacing the posterior lip. The cyst extended supravaginally and filled the posterior fornix. Magnetic resonance imaging suggested a 15 cm × 10 cm huge NC. Laparoscopic hysterectomy was done. There were difficulties in bladder dissection, ureteric identification, and vault delineation. The cyst contained 800 ml of clear fluid with a few milliliters of yellowish mucinous fluid. To our knowledge, NC of this size has not been reported in the literature. NCs are benign lesions, but they have to be differentiated from other cervical cysts - particularly malignant or premalignant lesions. NC can very well be managed laparoscopically, provided the skills of precise dissection are possessed by the surgeon.

Patient Impressions and Outcomes After Clinic-Based Hidradenitis Suppurativa Surgery.

IMPORTANCE: Surgical intervention is frequently needed to treat hidradenitis suppurativa (HS). Patient satisfaction is high based on previous studies, but reports of patient impressions of clinic-based operative experiences and postoperative recovery are limited. OBJECTIVE: To characterize patient impressions, outcomes, and recovery time after clinic-based surgical treatment of HS and examine patient characteristics associated with outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients 12 years or older who underwent clinic-based surgical procedures for treatment of HS at a single subspecialty HS clinic at the University of North Carolina Department of Dermatology from April 2014 to December 2018. Data analysis was performed from January to September 2021. EXPOSURES: Clinic-based deroofing and excisional procedures performed as part of routine care. MAIN OUTCOMES AND MEASURES: The primary outcomes were patient-reported recurrence of HS at the site of surgery, patient satisfaction with the procedures and outcomes, and patient-reported pain and recovery associated with surgery obtained from electronic medical record review and patient questionnaires. RESULTS: Outcomes of 194 procedures for 78 patients (65 [83%] female; mean [SD] age, 35.1 [12.1] years) were analyzed. Self-reported rate of recurrence was 41% (79 procedures). Despite recurrence, most patients (148 procedures [76%]) were very satisfied with their surgical results. The median number of missed days of work or school was 2 (IQR, 1-7 days), and the median number of days until return to normal activity was 10 (IQR, 3-14 days). In addition, for 126 of the 194 procedures (65%), patients stated that pain during an HS flare was worse than pain during surgical recovery. CONCLUSIONS AND RELEVANCE: In this cohort study, patients reported high rates of satisfaction with clinic-based HS surgery. Recovery was typically rapid, with most patients rating postsurgical pain as less severe than their HS pain.

Accessory Fallopian Tube in an Adolescent: A Rare Anomaly.

Accessory fallopian tube is a rare congenital/developmental anomaly, which has important clinical implications and is easily overlooked and missed by the surgeons. The incidence of this anomaly as stated in literature varies from 1.9% to almost 6% in infertile women. We report a case of a 14-year-old girl with dermoid cyst on the left ovary and with an accessory fallopian tube on the right side. The patient underwent laparoscopic dermoid cystectomy along with excision of the accessory fallopian tube. In spite of the presentation's rarity, gynecologists should be aware of such a condition as it has important clinical implications. The presence of an accessory tube predisposes to ectopic pregnancies, torsion, endometriosis, and infertility. Hence, routine careful inspection of the tubes, in any pelvic surgery, is recommended. Whenever encountered, it is advisable to excise these tubes after clear discussion of the implications.

Isolated Fallopian Tube Torsion: A Rare Twist with a Diagnostic Challenge That May Compromise Fertility.

Isolated Fallopian tube torsion (IFTT) is a rare entity with utmost important gynecological emergency with difficult preoperative diagnosis. Our aim is to analyze the clinical presentation, risk factors, and management of IFTT. We retrospectively analyzed all patients with intraoperative diagnosis of IFTT in our endogynecological department over a time period of 3 years and 6 months (January 2015-June 2018) in a tertiary level laparoscopic center. The clinical profile of the patients was analyzed and the results formulated. Statistical analysis was done by SPSS system, Version 15.00 (SPSS Inc., Chicago). A total 17 cases were diagnosed with IFTT with or without pathology. The mean age was 28.07 ± 11.3 years. Lower abdominal pain was the most common symptom (88%). About 47% had a history of tubal ligation. Salpingectomy was done in the majority of the patients (82.3%). Detorsion and preservation of the tube was possible in 17.6% of the cases. High index of suspicion is needed to diagnose this rare cause of acute abdomen. Hence, an early intervention can enhance the salvageability of the affected tubes which has a positive impact on the fertility status of the patients. Tubal preservation is the preferred procedure of choice whenever feasible.

Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of SCAR16.

CHIP (carboxyl terminus of heat shock 70-interacting protein) has long been recognized as an active member of the cellular protein quality control system given the ability of CHIP to function as both a co-chaperone and ubiquitin ligase. We discovered a genetic disease, now known as spinocerebellar autosomal recessive 16 (SCAR16), resulting from a coding mutation that caused a loss of CHIP ubiquitin ligase function. The initial mutation describing SCAR16 was a missense mutation in the ubiquitin ligase domain of CHIP (p.T246M). Using multiple biophysical and cellular approaches, we demonstrated that T246M mutation results in structural disorganization and misfolding of the CHIP U-box domain, promoting oligomerization, and increased proteasome-dependent turnover. CHIP-T246M has no ligase activity, but maintains interactions with chaperones and chaperone-related functions. To establish preclinical models of SCAR16, we engineered T246M at the endogenous locus in both mice and rats. Animals homozygous for T246M had both cognitive and motor cerebellar dysfunction distinct from those observed in the CHIP null animal model, as well as deficits in learning and memory, reflective of the cognitive deficits reported in SCAR16 patients. We conclude that the T246M mutation is not equivalent to the total loss of CHIP, supporting the concept that disease-causing CHIP mutations have different biophysical and functional repercussions on CHIP function that may directly correlate to the spectrum of clinical phenotypes observed in SCAR16 patients. Our findings both further expand our basic understanding of CHIP biology and provide meaningful mechanistic insight underlying the molecular drivers of SCAR16 disease pathology, which may be used to inform the development of novel therapeutics for this devastating disease.

Author Correction: Metformin reverses established lung fibrosis in a bleomycin model.

In the version of this article originally published, a grant was omitted from the Acknowledgements section. The following sentence should have been included: "R.B.M. was supported by a Department of Veterans Affairs Merit Award (5I01BX003272)." The error has been corrected in the HTML and PDF versions of this article.

Adverse Effects of Fenofibrate in Mice Deficient in the Protein Quality Control Regulator, CHIP.

We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, which was accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long-chain and medium-chain fatty acid metabolites in wild-type hearts. This response was attenuated in mice that lack expression of CHIP (CHIP-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism pathways that are regulated, in part, by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP-/- mice with the PPARα agonist called fenofibrate. We found that treating CHIP-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in decreased skeletal muscle mass, compared to wild-type mice, and a marked increase in cardiac fibrosis accompanied by a decrease in cardiac function. Fenofibrate resulted in decreased mitochondrial cristae density in CHIP-/- hearts as well as decreased expression of genes involved in the initiation of autophagy and mitophagy, which suggests that a metabolic challenge, in the absence of CHIP expression, impacts pathways that contribute to mitochondrial quality control. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected skeletal muscle and cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism.

Do supportive family behaviors promote diabetes self-management in resource limited urban settings? A cross sectional study.

BACKGROUND: Self-management is an essential component of prevention and treatment of type 2 diabetes. Social and family support has been shown to influence self-management behaviors as well as glycemic control and complications. This study was conducted to assess whether diabetes family support improves diabetes self-management and glycemic control in a typical urban population in India. METHODS: A cross-sectional study using a questionnaire that had items from the Summary of Diabetes Self Care Activities Scale (SDSCA), the Diabetes Family Behavior Checklist (DFBC) and some sociodemographic and diabetes related clinical data was conducted. The participants were consecutively sampled from the diabetes outpatient department in a tertiary care hospital in Chennai, south India. RESULTS: A total of 200 consecutive patients from the diabetes outpatient department were interviewed. Diabetes self-management practices were good with respect to avoiding fatty foods and carbohydrates and undergoing regular blood testing for glucose. But the self-management with respect to exercise and foot related care was rare. It was observed that a vast majority of the patients did not report receiving any support from their families. However, in the small proportion who did receive good family support, there is an association between diabetes self-management and diabetes family support (ß = 0.527; p = 0.015). Further, the path model showed that there is a positive statistically significant association between family support score and the diabetes self-management score (ß = 0.254, p < 0.001). However, the negative association between the diabetes self-management score and the mean plasma glucose did not reach statistical significance (ß = - 46.378, p = 0.082). CONCLUSIONS: In the urban south Indian setting, family support was significantly associated with better self-management activities, but better self-management did not reflect as better glycaemic control.

Metformin reverses established lung fibrosis in a bleomycin model.

Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1. Cellular metabolism regulates tissue repair and remodelling responses to injury2-4. AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5. However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.

Methods for assessing mitochondrial quality control mechanisms and cellular consequences in cell culture.

Mitochondrial quality is under surveillance by autophagy, the cell recycling process which degrades and removes damaged mitochondria. Inadequate autophagy results in deterioration in mitochondrial quality, bioenergetic dysfunction, and metabolic stress. Here we describe in an integrated work-flow to assess parameters of mitochondrial morphology, function, mtDNA and protein damage, metabolism and autophagy regulation to provide the framework for a practical assessment of mitochondrial quality. This protocol has been tested with cell cultures, is highly reproducible, and is adaptable to studies when cell numbers are limited, and thus will be of interest to researchers studying diverse physiological and pathological phenomena in which decreased mitochondrial quality is a contributory factor.

Clinical Evidence Supports a Protective Role for CXCL5 in Coronary Artery Disease.

Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating CXCL5 levels were measured from plasma, and both DNA genotyping and mRNA expression levels in peripheral blood mononuclear cells were quantified via microarray gene chips. We observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% CI, 0.27-0.75). Controlling for covariates, including sex, statin use, hypertension, hyperlipidemia, obesity, self-reported race, smoking, and diabetes, the OR was not significantly affected [OR, 0.54 (95% CI, 0.31-0.96)], consistent with a protective role for CXCL5 in coronary atherosclerosis. We also identified 18 genomic regions with expression quantitative trait loci of genes correlated with both CAD severity and circulating CXCL5 levels. Our clinical findings are consistent with the emerging link between chemokines and atherosclerosis and suggest new therapeutic targets for CAD.

Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons.

Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics. To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. We found that both bafilomycin and chloroquine could significantly increase the autophagosome marker LC3-II and inhibit key parameters of mitochondrial function, and increase mtDNA damage. Furthermore, we observed significant alterations in TCA cycle intermediates, particularly those downstream of citrate synthase and those linked to glutaminolysis. Taken together, these data demonstrate a significant impact of bafilomycin and chloroquine on cellular bioenergetics and metabolism consistent with decreased mitochondrial quality associated with inhibition of autophagy.

Maternal and birth risk factors for children screening positive for autism spectrum disorders on M-CHAT-R.

This study was carried out to screen children aged 16-30 months, attending pediatric outpatient department of JIPMER, Puducherry, during June to August 2014, for ASD using modified checklist for autism in toddlers-revised (MCHAT-R) and to find association between maternal, birth and postnatal risk factors with risk of ASD. A total of 350 mother-child pairs with children aged between 16 and 30 months were recruited. M-CHAT-R was administered to all mothers to screen for ASD along with risk checklist. Based on screen result children were classified as ASD (high risk) and no ASD (low and medium risk) group. The association between risk factors and screen positivity for ASD was studied using odds ratio. According to our study, 33 (9.4%) screened positive for ASD. Mean age was 21 months. High mean paternal age at birth (P value 0.025), need for resuscitation at birth (OR 3.4, 95% CI 1.47-8.10), NICU stay >12h (OR 4.7, 95% CI 2.26-9.94), late initiation of breastfeeding (OR 3.9, 95% CI 1.83-8.39), neonatal seizures (OR 11.8, 95% CI 5.38-26.25) were associated with screen positivity for ASD. After adjusting for confounding, neonatal seizures, and maternal concern about child development were associated with increased odds of screening positive for ASD whereas exclusive breast feeding in the first 6 months of life is associated with decreased odds. Screening for ASD in children with above risk factors might help in early initiation of remedial interventions.

Pleiotropic effects of 4-hydroxynonenal on oxidative burst and phagocytosis in neutrophils.

Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume large quantities of oxygen to rapidly generate ROS, a process that is referred to as the oxidative burst. These ROS are required for the efficient removal of phagocytized cellular debris and pathogens. In chronic inflammatory diseases, neutrophils are exposed to increased levels of oxidants and pro-inflammatory cytokines that can further prime oxidative burst responses and generate lipid oxidation products such as 4-hydroxynonenal (4-HNE). In this study we hypothesized that since 4-HNE can target glycolysis then this could modify the oxidative burst. To address this the oxidative burst was determined in freshly isolated healthy subject neutrophils using 13-phorbol myristate acetate (PMA) and the extracellular flux analyzer. Neutrophils pretreated with 4-HNE exhibited a significant decrease in the oxidative burst response and phagocytosis. Mass spectrometric analysis of alkyne-HNE treated neutrophils followed by click chemistry detected modification of a number of cytoskeletal, metabolic, redox and signaling proteins that are critical for the NADPH oxidase mediated oxidative burst. These modifications were confirmed using a candidate immunoblot approach for critical proteins of the active NADPH oxidase enzyme complex (Nox2 gp91phox subunit and Rac1 of the NADPH oxidase) and glyceraldehyde phosphate dehydrogenase, a critical enzyme in the metabolic regulation of oxidative burst. Taken together, these data suggest that 4-HNE-induces a pleiotropic mechanism to inhibit neutrophil function. These mechanisms may contribute to the immune dysregulation associated with chronic pathological conditions where 4-HNE is generated.

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation.

Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via ß-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented.

Modification of platelet proteins by 4-hydroxynonenal: Potential Mechanisms for inhibition of aggregation and metabolism.

Platelet aggregation is an essential response to tissue injury and is associated with activation of pro-oxidant enzymes, such as cyclooxygenase, and is also a highly energetic process. The two central energetic pathways in the cell, glycolysis and mitochondrial oxidative phosphorylation, are susceptible to damage by reactive lipid species. Interestingly, how platelet metabolism is affected by the oxidative stress associated with aggregation is largely unexplored. To address this issue, we examined the response of human platelets to 4-hydroxynonenal (4-HNE), a reactive lipid species which is generated during thrombus formation and during oxidative stress. Elevated plasma 4-HNE has been associated with renal failure, septic shock and cardiopulmonary bypass surgery. In this study, we found that 4-HNE decreased thrombin stimulated platelet aggregation by approximately 60%. The metabolomics analysis demonstrated that underlying our previous observation of a stimulation of platelet energetics by thrombin glycolysis and TCA (Tricarboxylic acid) metabolites were increased. Next, we assessed the effect of both 4-HNE and alkyne HNE (A-HNE) on bioenergetics and targeted metabolomics, and found a stimulatory effect on glycolysis, associated with inhibition of bioenergetic parameters. In the presence of HNE and thrombin glycolysis was further stimulated but the levels of the TCA metabolites were markedly suppressed. Identification of proteins modified by A-HNE followed by click chemistry and mass spectrometry revealed essential targets in platelet activation including proteins involved in metabolism, adhesion, cytoskeletal reorganization, aggregation, vesicular transport, protein folding, antioxidant proteins, and small GTPases. In summary, the biological effects of 4-HNE can be more effectively explained in platelets by the integrated effects of the modification of an electrophile responsive proteome rather than the isolated effects of candidate proteins.

Defining the effects of storage on platelet bioenergetics: The role of increased proton leak.

The quality of platelets decreases over storage time, shortening their shelf life and potentially worsening transfusion outcomes. The changes in mitochondrial function associated with platelet storage are poorly defined and to address this we measured platelet bioenergetics in freshly isolated and stored platelets. We demonstrate that the hypotonic stress test stimulates both glycolysis and oxidative phosphorylation and the stored platelets showed a decreased recovery to this stress. We found no change in aggregability between the freshly isolated and stored platelets. Bioenergetic parameters were changed including increased proton leak and decreased basal respiration and this was reflected in a lower bioenergetic health index (BHI). Mitochondrial electron transport, measured in permeabilized platelets, showed only minor changes which are unlikely to have a significant impact on platelet function. There were no changes in basal glycolysis between the fresh and stored platelets, however, glycolytic rate was increased in stored platelets when mitochondrial ATP production was inhibited. The increase in proton leak was attenuated by the addition of albumin, suggesting that free fatty acids could play a role in increasing proton leak and decreasing mitochondrial function. In summary, platelet storage causes a modest decrease in oxidative phosphorylation driven by an increase in mitochondrial proton leak, which contributes to the decreased recovery to hypotonic stress.

Metabolic Reprogramming Is Required for Myofibroblast Contractility and Differentiation.

Contraction is crucial in maintaining the differentiated phenotype of myofibroblasts. Contraction is an energy-dependent mechanism that relies on the production of ATP by mitochondria and/or glycolysis. Although the role of mitochondrial biogenesis in the adaptive responses of skeletal muscle to exercise is well appreciated, mechanisms governing energetic adaptation of myofibroblasts are not well understood. Our study demonstrates induction of mitochondrial biogenesis and aerobic glycolysis in response to the differentiation-inducing factor transforming growth factor ß1 (TGF-ß1). This metabolic reprogramming is linked to the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Inhibition of p38 MAPK decreased accumulation of active peroxisome proliferator-activated receptor γ coactivator 1α in the nucleus and altered the translocation of mitochondrial transcription factor A to the mitochondria. Genetic or pharmacologic approaches that block mitochondrial biogenesis or glycolysis resulted in decreased contraction and reduced expression of TGF-ß1-induced α-smooth muscle actin and collagen α-2(I) but not of fibronectin or collagen α-1(I). These data indicate a critical role for TGF-ß1-induced metabolic reprogramming in regulating myofibroblast-specific contractile signaling and support the concept of integrating bioenergetics with cellular differentiation.

Inhibition of the lymphocyte metabolic switch by the oxidative burst of human neutrophils.

Activation of the phagocytic NADPH oxidase-2 (NOX-2) in neutrophils is a critical process in the innate immune system and is associated with elevated local concentrations of superoxide, hydrogen peroxide (H2O2) and hypochlorous acid. Under pathological conditions, NOX-2 activity has been implicated in the development of autoimmunity, indicating a role in modulating lymphocyte effector function. Notably, T-cell clonal expansion and subsequent cytokine production requires a metabolic switch from mitochondrial respiration to aerobic glycolysis. Previous studies demonstrate that H2O2 generated from activated neutrophils suppresses lymphocyte activation but the mechanism is unknown. We hypothesized that activated neutrophils would prevent the metabolic switch and suppress the effector functions of T-cells through a H2O2-dependent mechanism. To test this, we developed a model co-culture system using freshly isolated neutrophils and lymphocytes from healthy human donors. Extracellular flux analysis was used to assess mitochondrial and glycolytic activity and FACS analysis to assess immune function. The neutrophil oxidative burst significantly inhibited the induction of lymphocyte aerobic glycolysis, caused inhibition of oxidative phosphorylation and suppressed lymphocyte activation through a H2O2-dependent mechanism. Hydrogen peroxide and a redox cycling agent, DMNQ, were used to confirm the impact of H2O2 on lymphocyte bioenergetics. In summary, we have shown that the lymphocyte metabolic switch from mitochondrial respiration to glycolysis is prevented by the oxidative burst of neutrophils. This direct inhibition of the metabolic switch is then a likely mechanism underlying the neutrophil-dependent suppression of T-cell effector function.