Testing prescribed burning to shift an agronomic grass community to a diverse native plant community.

Prescribed burning can be an effective land management tool. Here, we study changes in plant diversity and composition following experimental fire disturbance in microcosm units extracted from a twenty-five-year-old historically reclaimed grassland located at Highland Valley Copper mine in British Columbia (B.C.), Canada. Experimental microcosm units were dominated by agronomic grass species Elymus lanceolatus, Thinopyrum intermedium and Bromus inermis. The disturbance treatment was fire intensity, represented by three levels (light, moderate, and heavy), replicated six times per treatment. Fire intensity was controlled by modifying the weight of dried litter applied to each microcosm unit (50 g,150 g, 200g), along with the time each grass turf was burned (10 s, 15 s, 20 s). One day after the fire treatment was applied, microcosm units were seeded with a native species mix consisting of six grassland species common to southern B.C. to examine effectiveness of plant establishment postburn. Disturbance treatments resulted in higher overall alpha diversity, richness, evenness, and beta diversity. Plant community changes included colonization of seeded native forbs, grasses, and legumes in response to disturbance. Aboveground net primary productivity (ANPP) was net neutral within the light and moderate burning disturbance treatments but resulted in increased ANPP with heavy disturbance. Litter mass reduced plant diversity and ANPP, indicating that litter was a major factor in plant community dynamics. These results suggest disturbance by burning leads to short term positive plant community response towards increasing diversity of semi-arid grasslands, and aids in shifting plant communities to higher diversity composed of an increase in native plant species. Our results also suggest that without active management the gains observed in native species establishment might quickly be out shadowed and restricted by the previously dominant agronomic plant community.

Designing Actionable Solutions and Curriculum for Pain Disparities Education.

The Liaison Committee on Medical Education (LCME) require medical schools to teach their students how to recognize and work toward eliminating health disparities. However, time constraints and a dearth of guidance for educators in teaching pain disparities curricula pose significant challenges. Herein we describe successes and lessons learned after designing, implementing, and evaluating an innovative pain disparities curriculum that was embedded in a longitudinal health equity curriculum for third year medical school students at an academic institution. Although the curriculum was developed for medical school students, the concepts may be broadly applicable to other training settings such as residency and fellowship programs.

Effects of Axonal Demyelination, Inflammatory Cytokines and Divalent Cation Chelators on Thalamic HCN Channels and Oscillatory Bursting.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is characterized by the progressive loss of oligodendrocytes and myelin and is associated with thalamic dysfunction. Cuprizone (CPZ)-induced general demyelination in rodents is a valuable model for studying different aspects of MS pathology. CPZ feeding is associated with the altered distribution and expression of different ion channels along neuronal somata and axons. However, it is largely unknown whether the copper chelator CPZ directly influences ion channels. Therefore, we assessed the effects of different divalent cations (copper; zinc) and trace metal chelators (EDTA; Tricine; the water-soluble derivative of CPZ, BiMPi) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that are major mediators of thalamic function and pathology. In addition, alterations of HCN channels induced by CPZ treatment and MS-related proinflammatory cytokines (IL-1ß; IL-6; INF-α; INF-ß) were characterized in C57Bl/6J mice. Thus, the hyperpolarization-activated inward current (Ih) was recorded in thalamocortical (TC) neurons and heterologous expression systems (mHCN2 expressing HEK cells; hHCN4 expressing oocytes). A number of electrophysiological characteristics of Ih (potential of half-maximal activation (V0.5); current density; activation kinetics) were unchanged following the extracellular application of trace metals and divalent cation chelators to native neurons, cell cultures or oocytes. Mice were fed a diet containing 0.2% CPZ for 35 days, resulting in general demyelination in the brain. Withdrawal of CPZ from the diet resulted in rapid remyelination, the effects of which were assessed at three time points after stopping CPZ feeding (Day1, Day7, Day25). In TC neurons, Ih was decreased on Day1 and Day25 and revealed a transient increased availability on Day7. In addition, we challenged naive TC neurons with INF-α and IL-1ß. It was found that Ih parameters were differentially altered by the application of the two cytokines to thalamic cells, while IL-1ß increased the availability of HCN channels (depolarized V0.5; increased current density) and the excitability of TC neurons (depolarized resting membrane potential (RMP); increased the number of action potentials (APs); produced a larger voltage sag; promoted higher input resistance; increased the number of burst spikes; hyperpolarized the AP threshold), INF-α mediated contrary effects. The effect of cytokine modulation on thalamic bursting was further assessed in horizontal slices and a computational model of slow thalamic oscillations. Here, IL-1ß and INF-α increased and reduced oscillatory bursting, respectively. We conclude that HCN channels are not directly modulated by trace metals and divalent cation chelators but are subject to modulation by different MS-related cytokines.

Chalcones bearing a 3,4,5-trimethoxyphenyl motif are capable of selectively inhibiting oncogenic K-Ras signaling.

Ras proteins are small GTPases which regulate cellular proliferation, differentiation, and apoptosis. Constitutively active mutant Ras are expressed in ~15-20% human cancers, and K-Ras mutations account for ~85% of all Ras mutations. Despite the significance of Ras proteins in refractory cancers, there is no anti-Ras drug available in clinic. Since K-Ras must interact with the plasma membrane (PM) for biological activity, inhibition of the K-Ras/PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we discovered chalcones 1 and 8 exhibit anti-K-Ras activity, and show that the compounds mislocalize K-Ras from the PM and block oncogenic K-Ras signal output. Also, 1 inhibits the growth of K-Ras-driven human cancer cells. Our data suggest that 1 could be a promising starting point for developing anti-K-Ras cancer drug.

A Phosphate-Dependent Requirement for Transcription Factors IPD3 and IPD3L During Arbuscular Mycorrhizal Symbiosis in Medicago truncatula.

During arbuscular mycorrhizal (AM) symbiosis, activation of a symbiosis signaling pathway induces gene expression necessary for accommodation of AM fungi. Here, we focus on pathway components Medicago truncatula INTERACTING PROTEIN OF DOES NOT MAKE INFECTIONS 3 (IPD3) and IPD3 LIKE (IPD3L), which are potential orthologs of Lotus japonicus CYCLOPS, a transcriptional regulator essential for AM symbiosis. In the double mutant ipd3 ipd3l, hyphal entry through the epidermis and overall colonization levels are reduced relative to the wild type but fully developed arbuscules are present in the cortex. In comparison with the wild type, colonization of ipd3 ipd3l is acutely sensitive to higher phosphate levels in the growth medium, with a disproportionate decrease in epidermal penetration, overall colonization, and symbiotic gene expression. When constitutively expressed in ipd3 ipd3l, an autoactive DOES NOT MAKE INFECTIONS 3 induces the expression of transcriptional regulators REDUCED ARBUSCULAR MYCORRHIZA 1 and REQUIRED for ARBUSCULE DEVELOPMENT 1, providing a possible avenue for arbuscule development in the absence of IPD3 and IPD3L. An increased sensitivity of ipd3 ipd3l to GA3 suggests an involvement of DELLA. The data reveal partial redundancy in the symbiosis signaling pathway, which may ensure robust signaling in low-phosphorus environments, while IPD3 and IPD3L maintain signaling in higher-phosphorus environments. The latter may buffer the pathway from short-term variation in phosphorus levels encountered by roots during growth in heterogeneous soil environments.

Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159.

Despite continuous efforts to control cariogenic dental biofilms, very few effective antimicrobial treatments exist. In this study, we characterized the activity of the novel synthetic cyclic lipopeptide 4 (CLP-4), derived from fusaricidin, against the cariogenic pathogen Streptococcus mutans UA159. We determined CLP-4's MIC, minimum bactericidal concentration (MBC), and spontaneous resistance frequency, and we performed time-kill assays. Additionally, we assessed CLP-4's potential to inhibit biofilm formation and eradicate preformed biofilms. Our results demonstrate that CLP-4 has strong antibacterial activity in vitro and is a potent bactericidal agent with low spontaneous resistance frequency. At a low concentration of 5 µg/ml, CLP-4 completely inhibited S. mutans UA159 biofilm formation, and at 50 µg/ml, it reduced the viability of established biofilms by >99.99%. We also assessed CLP-4's cytotoxicity and stability against proteolytic digestion. CLP-4 withstood trypsin or chymotrypsin digestion even after treatment for 24 h, and our toxicity studies showed that CLP-4 effective concentrations had negligible effects on hemolysis and the viability of human oral fibroblasts. In summary, our findings showed that CLP-4 is a potent antibacterial and antibiofilm agent with remarkable stability and low nonspecific cytotoxicity. Hence, CLP-4 is a promising novel antimicrobial peptide with potential for clinical application in the prevention and treatment of dental caries.

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.

BACKGROUND: Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. AIMS: To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS). MATERIALS & METHODS: Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. RESULTS: Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05). DISCUSSION: Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. CONCLUSION: Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism.

The coding and noncoding architecture of the Caulobacter crescentus genome.

Caulobacter crescentus undergoes an asymmetric cell division controlled by a genetic circuit that cycles in space and time. We provide a universal strategy for defining the coding potential of bacterial genomes by applying ribosome profiling, RNA-seq, global 5'-RACE, and liquid chromatography coupled with tandem mass spectrometry (LC-MS) data to the 4-megabase C. crescentus genome. We mapped transcript units at single base-pair resolution using RNA-seq together with global 5'-RACE. Additionally, using ribosome profiling and LC-MS, we mapped translation start sites and coding regions with near complete coverage. We found most start codons lacked corresponding Shine-Dalgarno sites although ribosomes were observed to pause at internal Shine-Dalgarno sites within the coding DNA sequence (CDS). These data suggest a more prevalent use of the Shine-Dalgarno sequence for ribosome pausing rather than translation initiation in C. crescentus. Overall 19% of the transcribed and translated genomic elements were newly identified or significantly improved by this approach, providing a valuable genomic resource to elucidate the complete C. crescentus genetic circuitry that controls asymmetric cell division.

A comparison of facemask and respirator filtration test methods.

NIOSH published a Federal Register Notice to explore the possibility of incorporating FDA required filtration tests for surgical masks (SMs) in the 42 CFR Part 84 respirator certification process. There have been no published studies comparing the filtration efficiency test methods used for NIOSH certification of N95 filtering facepiece respirators (N95 FFRs) with those used by the FDA for clearance of SMs. To address this issue, filtration efficiencies of "N95 FFRs" including six N95 FFR models and three surgical N95 FFR models, and three SM models were measured using the NIOSH NaCl aerosol test method, and FDA required particulate filtration efficiency (PFE) and bacterial filtration efficiency (BFE) methods, and viral filtration efficiency (VFE) method. Five samples of each model were tested using each method. Both PFE and BFE tests were done using unneutralized particles as per FDA guidance document. PFE was measured using 0.1 µm size polystyrene latex particles and BFE with ∼3.0 µm size particles containing Staphylococcus aureus bacteria. VFE was obtained using ∼3.0 µm size particles containing phiX 174 as the challenge virus and Escherichia coli as the host. Results showed that the efficiencies measured by the NIOSH NaCl method for "N95 FFRs" were from 98.15-99.68% compared to 99.74-99.99% for PFE, 99.62-99.9% for BFE, and 99.8-99.9% for VFE methods. Efficiencies by the NIOSH NaCl method were significantly (p = <0.05) lower than the other methods. SMs showed lower efficiencies (54.72-88.40%) than "N95 FFRs" measured by the NIOSH NaCl method, while PFE, BFE, and VFE methods produced no significant difference. The above results show that the NIOSH NaCl method is relatively conservative and is able to identify poorly performing filtration devices. The higher efficiencies obtained using PFE, BFE and VFE methods show that adding these supplemental particle penetration methods will not improve respirator certification.

FLEXc: protein flexibility prediction using context-based statistics, predicted structural features, and sequence information.

BACKGROUND: The fluctuation of atoms around their average positions in protein structures provides important information regarding protein dynamics. This flexibility of protein structures is associated with various biological processes. Predicting flexibility of residues from protein sequences is significant for analyzing the dynamic properties of proteins which will be helpful in predicting their functions. RESULTS: In this paper, an approach of improving the accuracy of protein flexibility prediction is introduced. A neural network method for predicting flexibility in 3 states is implemented. The method incorporates sequence and evolutionary information, context-based scores, predicted secondary structures and solvent accessibility, and amino acid properties. Context-based statistical scores are derived, using the mean-field potentials approach, for describing the different preferences of protein residues in flexibility states taking into consideration their amino acid context. The 7-fold cross validated accuracy reached 61 % when context-based scores and predicted structural states are incorporated in the training process of the flexibility predictor. CONCLUSIONS: Incorporating context-based statistical scores with predicted structural states are important features to improve the performance of predicting protein flexibility, as shown by our computational results. Our prediction method is implemented as web service called "FLEXc" and available online at: http://hpcr.cs.odu.edu/flexc .

Precision medicine in alcoholic and nonalcoholic fatty liver disease via modulating the gut microbiota.

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) represent a major health burden in industrialized countries. Although alcohol abuse and nutrition play a central role in disease pathogenesis, preclinical models support a contribution of the gut microbiota to ALD and NAFLD. This review describes changes in the intestinal microbiota compositions related to ALD and NAFLD. Findings from in vitro, animal, and human studies are used to explain how intestinal pathology contributes to disease progression. This review summarizes the effects of untargeted microbiome modifications using antibiotics and probiotics on liver disease in animals and humans. While both affect humoral inflammation, regression of advanced liver disease or mortality has not been demonstrated. This review further describes products secreted by Lactobacillus- and microbiota-derived metabolites, such as fatty acids and antioxidants, that could be used for precision medicine in the treatment of liver disease. A better understanding of host-microbial interactions is allowing discovery of novel therapeutic targets in the gut microbiota, enabling new treatment options that restore the intestinal ecosystem precisely and influence liver disease. The modulation options of the gut microbiota and precision medicine employing the gut microbiota presented in this review have excellent prospects to improve treatment of liver disease.

Identification of activators of methionine sulfoxide reductases A and B.

The methionine sulfoxide reductase (Msr) family of enzymes has been shown to protect cells against oxidative damage. The two major Msr enzymes, MsrA and MsrB, can repair oxidative damage to proteins due to reactive oxygen species, by reducing the methionine sulfoxide in proteins back to methionine. A role of MsrA in animal aging was first demonstrated in Drosophila melanogaster where transgenic flies over-expressing recombinant bovine MsrA had a markedly extended life span. Subsequently, MsrA was also shown to be involved in the life span extension in Caenorhabditis elegans. These results supported other studies that indicated up-regulation, or activation, of the normal cellular protective mechanisms that cells use to defend against oxidative damage could be an approach to treat age related diseases and slow the aging process. In this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB.

ClpXP and ClpAP proteolytic activity on divisome substrates is differentially regulated following the Caulobacter asymmetric cell division.

Proteolytic control of Caulobacter cell cycle proteins is primarily executed by ClpXP, a dynamically localized protease implicated in turnover of several factors critical for faithful cell cycle progression. Here, we show that the transient midcell localization of ClpXP that precedes cytokinesis requires the FtsZ component of the divisome. Although ClpAP does not exhibit subcellular localization, FtsZ is a substrate of both ClpXP and ClpAP in vivo and in vitro. A peptide containing the C-terminal portion of the FtsA divisome protein is a substrate of both ClpXP and ClpAP in vitro but is primarily degraded by ClpAP in vivo. Caulobacter carries out an asymmetric division in which FtsZ and FtsA are stable in stalked cells but degraded in the non-replicative swarmer cell where ClpAP alone degrades FtsA and both ClpAP and ClpXP degrade FtsZ. While asymmetric division in Caulobacter normally yields larger stalked and smaller swarmer daughters, we observe a loss of asymmetric size distribution among daughter cells when clpA is depleted from a strain in which FtsZ is constitutively produced. Taken together, these results suggest that the activity of both ClpXP and ClpAP on divisome substrates is differentially regulated in daughter cells.

Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice.

Obesity triggers a low-grade systemic inflammation, which plays an important role in the development of obesity-associated metabolic diseases. In searching for links between lipid accumulation and chronic inflammation, we examined invariant natural killer T (iNKT) cells, a subset of T lymphocytes that react with lipids and regulate inflammatory responses. We show that iNKT cells respond to dietary lipid excess and become activated before or at the time of tissue recruitment of inflammatory leukocytes, and that these cells progressively increase proinflammatory cytokine production in obese mice. Such iNKT cells skew other leukocytes toward proinflammatory cytokine production and induce an imbalanced proinflammatory cytokine environment in multiple tissues. Further, iNKT cell deficiency ameliorates tissue inflammation and provides protection against obesity-induced insulin resistance and hepatic steatosis. Conversely, chronic iNKT cell stimulation using a canonical iNKT cell agonist exacerbates tissue inflammation and obesity-associated metabolic disease. These findings place iNKT cells into the complex network linking lipid excess to inflammation in obesity and suggest new therapeutic avenues for obesity-associated metabolic disorders.

Planned Bone Resections Using an MRI-Based Custom Cutting Guide System Versus 3-Dimensional, Weight-Bearing Images in Total Knee Arthroplasty.

Potential sources of alignment variability not yet investigated with the use of custom cutting guides (CCG) in total knee arthroplasty (TKA) are weight-bearing and lower extremity rotation. This study compared the preoperative planned bone resections created using an MRI-based CCG system to those from 3-dimensional, weight-bearing, full-length lower extremity images in 53 patients undergoing TKA. The angular difference between the proposed resections of the two systems was greater than 2° in 30.2% of patients for the distal femur, and 52.8% for the proximal tibia. An increased preoperative varus alignment had a slight association with an increased angular difference for the tibial resection (r=0.4). This study demonstrates weight-bearing and lower extremity rotation to be potential sources of alignment variability when using MRI-based CCGs.

Non-Operative Approach to Contained Perforated Marginal Ulcers: A Systematic Review and Case Series.

BACKGROUND: Perforated marginal ulcers (PMUs) are a rare but known complication of bariatric surgery. Management typically involves prompt surgical intervention, but limited data exists on non-operative approaches. This study reviews published data on non-operative management of PMUs and presents a case series of patients who were managed non-operatively. Our hypothesis is that certain patients with signs of perforation can be successfully managed non-operatively with close observation. METHODS: We completed a systematic review searching PubMed, Embase, Web of Science, Cochrane, and clinicaltrials.gov. Ultimately 3 studies described the presentation and non-operative management of 5 patients. Additionally, we prospectively collected data from our institution on all patients who presented between Dec. 2022 and Dec. 2023 with PMUs confirmed on imaging and managed non-operatively. RESULTS: In our literature review, three patients had Roux-en-Y gastric bypass (RYGB), while two had one anastomosis gastric bypass. One patient required surgery two days after admission. Another underwent elective conversion surgery weeks later for a non-healing ulcer. Two received endoscopic interventions. One patient recovered with nil-per-os (NPO) status, and intravenous proton pump inhibitor (PPI) treatment. The patients in our case series presented with normal vital signs, an average of 30 months after RYGB, and with CT scan signs of perforation. None of these patients required surgical or endoscopic intervention. CONCLUSION: In conclusion, while perforated marginal ulcers have traditionally been considered a surgical emergency, some patients can be successfully treated with non-operative management. More research is needed to identify the clinical presentation features, comorbidities, and imaging findings of this group.

In-Space Fabrication of Janus Base Nano-Matrix for Improved Assembly and Bioactivities.

In-space manufacturing of nanomaterials is a promising concept while having limited successful examples. DNA-inspired Janus base nanomaterials (JBNs), used for therapeutics delivery and tissue regeneration, are fabricated via a controlled self-assembly process in water at ambient temperature, making them highly suitable for in-space manufacturing. For the first time, we designed and accomplished the production of JBNs on orbit during the Axiom-2 (Ax-2) mission demonstrating great promising and benefits of in-space manufacturing of nanomaterials.

Assessing neuroprotective effects of diroximel fumarate and siponimod via modulation of pacemaker channels in an experimental model of remyelination.

Cuprizone (CPZ)-induced alterations in axonal myelination are associated with a period of neuronal hyperexcitability and increased activity of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in the thalamocortical (TC) system. Substances used for the treatment of multiple sclerosis (MS) have been shown to normalize neuronal excitability in CPZ-treated mice. Therefore, we aimed to examine the effects of diroximel fumarate (DRF) and the sphingosine 1-phospate receptor (S1PR) modulator siponimod on action potential firing and the inward current (Ih) carried by HCN ion channels in naive conditions and during different stages of de- and remyelination. Here, DRF application reduced Ih current density in ex vivo patch clamp recordings from TC neurons of the ventrobasal thalamic complex (VB), thereby counteracting the increase of Ih during early remyelination. Siponimod reduced Ih in VB neurons under control conditions but had no effect in neurons of the auditory cortex (AU). Furthermore, siponimod increased and decreased AP firing properties of neurons in VB and AU, respectively. Computational modeling revealed that both DRF and siponimod influenced thalamic bursting during early remyelination by delaying the onset and decreasing the interburst frequency. Thus, substances used in MS treatment normalize excitability in the TC system by influencing AP firing and Ih.

Cardiometabolic Improvements After Metabolic Surgery and Related Presurgery Factors.

Context: Metabolic surgery remains the most effective and durable treatment for severe obesity and related metabolic diseases. Objective: We examined cardiometabolic improvements after metabolic surgery and associated presurgery demographic and clinical factors in a large multiracial cohort. Methods: Included were 7804 patients (20-79 years) undergoing first-time metabolic surgery at Vanderbilt University Medical Center from 1999 to 2022. Pre- and 1-year postsurgery cardiometabolic profiles were extracted from medical records, including body mass index (BMI), blood pressure, blood lipids, glucose, and hemoglobin A1c. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated per American College of Cardiology/American Heart Association equations. Pre- to postsurgery cardiometabolic profiles were compared by paired t-test, and associated factors were identified by multivariable linear and logistic regression. Results: Among 7804 patients, most were women and White, while 1618 were men and 1271 were Black; median age and BMI were 45 years [interquartile range (IQR): 37-53] and 46.4 kg/m2 (IQR: 42.1-52.4). At 1-year postsurgery, patients showed significant decreases in systolic blood pressure (10.5 [95% confidence interval: 10.1, 10.9] mmHg), total cholesterol (13.5 [10.3, 16.7] mg/dL), glucose (13.6 [12.9, 14.4] mg/dL), hemoglobin A1c (1.13% [1.06, 1.20]), and 10-year ASCVD risk (absolute reduction: 1.58% [1.22, 1.94]; relative reduction: 34.4% [29.4, 39.3]); all P < .0001. Older, male, or Black patients showed less reduction in 10-year ASCVD risk and lower odds of diabetes/hypertension/dyslipidemia remission than younger, female, or White patients. Patients with a history of diabetes, hypertension, dyslipidemia, or cardiovascular disease showed less cardiometabolic improvements than those without. Results were similar with or without further adjusting for weight loss and largely sustained at 2-year postsurgery. Conclusion: Metabolic surgery results in significant cardiometabolic improvements, particularly among younger, female, or White patients and those without comorbidities.