Browsing by Author "Rao, Sangeeta, committee member"
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Item Open Access Bovine tuberculosis surveillance at cattle abattoirs in Ireland, 2008(Colorado State University. Libraries, 2017) Gompo, Tulsi Ram, author; Olea-Popelka, Francisco, advisor; Rao, Sangeeta, committee member; Henao-Tamayo, Marcela, committee memberBovine tuberculosis (TB) surveillance is an ongoing program among abattoirs (slaughterhouses) in Ireland. It is a key complementary tool in addition to the tuberculin skin test to detect infected herds. A retrospective cross-sectional study was conducted to assess the association between potential risk factors and the risk of detection, and the subsequent risk of confirmation of bovine TB lesions for cattle slaughtered in 2008 in Irish abattoirs. Consequently, the abattoirs were ranked based on their efficiencies of detecting suspected bovine TB lesions and their subsequent confirmation in laboratory. A database containing cattle records was obtained from the Center for Veterinary Epidemiology and Risk Analysis (CVERA) at University College Dublin, Ireland, that includes the results of animal movements, tuberculin test results, number of suspected bovine TB lesions detected during slaughter of animals and number of lesions confirmed as Mycobacterium bovis (M. bovis) in laboratory. The known potential risk factors impacting bovine TB lesions detection in Irish abattoirs were animal and herd level characteristics: age, sex, herd type, length of time a herd free from bovine TB after restriction, animal origin and District Electoral Division (DED) risk class. The data were analyzed to control for these potential risk factors when assessing the probability of detecting suspected bovine TB lesions among abattoirs in Ireland. Descriptive analysis was performed to assess the distribution of cattle slaughtered over the different abattoir. Univariable logistic regression was applied to evaluate an association between the risk factors and detection of bovine TB lesions in the abattoirs. Multivariable logistic regression analysis was performed to calculate the adjusted risk of bovine TB lesion detection and confirmation for each abattoir. During 2008, a total of 1,362,195 attested cattle were slaughtered in total thirty-five abattoirs in Ireland. Overall, 3,437 lesions (0.25%, or 25 per 10,000 slaughtered cattle) were detected, and from these, 2,187 (62.68%) bovine TB lesions were confirmed as caused by M. bovis in the laboratory. The crude detection risks varied from 0 to 56 lesions per 10,000 animals slaughtered. The average crude confirmation risks ranged from 0 to 100%. Ultimately, the abattoirs were ranked (1 being the best and 35 the worst) according to their effectiveness of bovine TB lesions detection and confirmation after adjusting the potential risk factors. There is a considerable variability in efficiencies of Irish abattoirs in detecting and confirming bovine TB lesions. It is thus recommended that Irish abattoirs should be monitored regularly with regards their bovine TB slaughter surveillance effectiveness. Also, the abattoirs with lower than expected effectiveness should be strengthened in order to meet the required standards of the Irish bovine TB slaughter surveillance program.Item Embargo Cardiovascular-protective effects of blueberry consumption in postmenopausal women with above-normal blood pressure(Colorado State University. Libraries, 2023) Woolf, Emily K., author; Johnson, Sarah A., advisor; Gentile, Christopher L., committee member; Weir, Tiffany L., committee member; Rao, Sangeeta, committee memberEndothelial dysfunction is the first step in atherosclerosis and contributes to its progression, and thus, is central to cardiovascular disease (CVD). It is driven by excessive oxidative stress and inflammation and characterized by impaired endothelium-dependent dilation. Estrogen-deficient postmenopausal women have oxidative stress-mediated suppression of endothelial function that is worsened by high blood pressure. Chronic blueberry consumption may be a beneficial dietary intervention for this population as it has shown to improve vascular function and blood pressure, though some studies have not demonstrated efficacy possibly due to the observed high interindividual variability in response to the intervention. Evidence indicates blueberries improve endothelial function, but studies have not been performed in postmenopausal women. Furthermore, ex vivo research has shown that blueberry (poly)phenols and their metabolites can decrease endothelial oxidative stress and inflammation, but whether these mechanisms translate to humans is unclear. The objectives of this dissertation were to 1) examine the efficacy of chronic blueberry consumption to improve endothelial function and blood pressure in estrogen-deficient postmenopausal women with above-normal blood pressure, with a specific focus on identifying mechanisms for improving endothelial function, 2) identify factors that contributed to the efficacy of blueberries as a dietary intervention for improving endothelial function, and 3) explore cellular mechanisms responsible for endothelial function improvements and the anti-atherogenic potential of blueberries. To investigate the aforementioned, we conducted a randomized, double-blind, placebo-controlled clinical trial and assessed endothelial function (measured through flow-mediated dilation (FMD)) and supine brachial blood pressure before and after daily consumption of 22 g of freeze-dried highbush blueberry powder or isocaloric placebo powder for 12 weeks. To examine mechanisms for improved endothelial function, FMD was assessed before and after infusing a supraphysiological dose of the antioxidant ascorbic acid (i.e. vitamin C) and normalized to shear rate area under the curve (FMD/SRAUC). To investigate factors impacting the interindividual variability in the endothelial function responses after the 12 weeks of blueberry consumption, we grouped the blueberry treatment group into responders (≥ +1% unit Δ FMD) and non-responders (< +1% unit Δ FMD) and performed secondary statistical analyses using data produced from the clinical trial. Lastly, to investigate mechanisms for improvements in endothelial function, we used a reverse translational human-to-cell approach leveraging human blood serum collected from participants in the clinical trial to perform ex vivo cell culture experiments. Results from the clinical trial showed that daily blueberry consumption significantly improved FMD/SRAUC compared to baseline by 96%. FMD not normalized for shear rate increased by 1.34% though the effects were not statistically significant (but were clinically significant). Improvements in FMD/SRAUC after blueberry consumption were due to reductions in oxidative stress as responses to ascorbic acid infusion were significantly reduced at 12 weeks in the blueberry group compared to baseline, with no changes in the placebo group. There were no major effects on blood pressure, arterial stiffness, endothelial cell protein expression, or other blood biomarkers of cardiovascular health. It was determined that the blueberry intervention was ~50% effective for improving FMD to clinically relevant levels of ≥ +1%, and that responders had decreased cardiovascular health and higher levels of circulating estrogen at baseline compared to non-responders. After 12 weeks of blueberry consumption, responders had reductions in oxidative stress, lower plasma nitrate levels, and higher phosphorylated endothelial nitric oxide synthase protein expression compared to non-responders. Lastly, we cultured HAECs with 15% serum (blueberry and placebo) for 1 h followed by 200 µM hydrogen peroxide (H2O2) for 24 h to induce endothelial dysfunction and evaluated the effects of blueberry (poly)phenol-rich serum on endothelial cell dysfunction and atherosclerosis progression. There were no statistically significant differences on monocyte binding, insulin-stimulated nitric oxide production, or peroxynitrite concentrations between dysfunctional HAECs treated with blueberry and placebo serum from the clinical trial. Collectively, results from these studies indicate that daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress, and that efficacy (i.e. degree to which postmenopausal women responded to treatment in endothelial function) seems to be dependent on participant characteristics including cardiovascular risk factors and estradiol at baseline. Due to the inconclusive results regarding the ex vivo experiment, cellular mechanisms by which blueberry (poly)phenol metabolites impact endothelial function and atherosclerosis progression cannot be determined.Item Open Access Characterization, quantification, and behavior of neoplastic monoclonal gammopathies in dogs and cats(Colorado State University. Libraries, 2022) Jeffries, Christina Michelle, author; Moore, A. Russell, advisor; Avery, Paul, advisor; Rao, Sangeeta, committee member; Vickery, Kate, committee memberMonoclonal immunoglobulin (M-protein) production can occur in a number of myeloma related diseases (MRD) in domestic animals, including multiple myeloma (MM), extramedullary plasmacytomas, solitary osseous plasmacytoma, IgM Waldenstroms macroglobulinemia/lymphoplasmacytic lymphoma, immunoglobulin secreting lymphomas and leukemias, and plasma cell leukemia. This thesis seeks to improve upon the current knowledge of MRDs by examining diagnostic methods, possible biases (such as hyperproteinemia), and by describing a large population of dogs and cats with confirmed M-proteins. Differentiation of polyclonal and monoclonal gammopathies can be achieved by serum protein electrophoresis (SPE) and immunofixation (IF). Agarose gel electrophoresis (AGE) is the most commonly used SPE method within veterinary medicine and a previous study validated a method for AGE SPE densitometric M-protein (dM-protein) quantification. Capillary zone electrophoresis (CZE) is another method of SPE that can be performed more rapidly than AGE SPE that may have increased sensitivity with similar specificity. We sought to compare these two methods of SPE to determine if CZE SPE is a comparable alternative method for dM-protein quantification in dogs and cats. We found that these methods performed similarly, and both appear to be acceptable methods for dM-protein quantification, but they should not be used interchangeably. This finding indicates that the previously published method for dM-protein quantification can also be used with CZE SPE in dogs and cats. Hyperglobulinemia, hyperproteinemia, and hypoalbuminemia are frequently used criteria to prompt SPE in dogs and cats, but M-protein production can occur in humans and animals without these criteria being met. The assumption that these criteria need to be present to raise concern for M-protein production may lead to delayed diagnosis in patients that have early MRD or low concentration M-protein production. Retrospective evaluation of samples submitted to our lab for SPE and IF between January 2014 and December 2019 identified 18 cases of confirmed M-proteins in dogs with normal total protein concentrations. Most of these animals had confirmed, or suspected, myeloma related disease or lymphoproliferative disorders which prompted SPE. A subset of these cases were evaluated to highlight the diagnostic utility of IF in cases with low concentration M-proteins. In all 7 cases evaluated, IF was needed to make a definitive diagnosis of an M-protein. Based on these findings, we recommend running SPE and IF in tandem to increase diagnostic accuracy for M-protein detection. Large studies characterizing dogs with monoclonal immunoglobulins are rare within the literature, with the largest study by Matus et al from 1984 describing 60 dogs with MM. We sought to retrospectively evaluate a large population of dogs with SPE and IF confirmed M-proteins to add to the available literature, evaluate previously published MM prognostic indicators, assess for novel prognostic indicators, and evaluate other clinicopathology and clinical variables. 113 canine cases were included in our analysis with a total of 75 cases having complete medical records available for analysis. MM was the most common diagnosis within our population, with fewer cases falling under the spectrum of MRD. The mean age of animals diagnosed with an M-protein was 9.9 years. Treatment of MM with prednisone and melphalan led to statistically longer MSTs in these cases when compared to single agent therapy with prednisone or melphalan. Clinical signs were frequently non-specific, but some cases presented with clinical signs that are potentially more specific for MRD such as collapse, evidence of bleeding diathesis, and musculoskeletal pain. Ancillary diagnostic testing such as PCR for antigen receptor rearrangement (PARR), flow cytometry, and/or immunohistochemistry/immunocytochemistry was required in some cases to fully categorize disease. Adoption of visceral organ involvement as a primary or alternative diagnostic criterion for MM may be more likely to appropriately categorize animals with MM, at least based on the clinical course of disease. Animals within our population also frequently had total hypercalcemia, proteinuria, and occasionally had renal dysfunction. Frequently used negative prognostic indicators failed to demonstrate statistical significance (except for renal disease), but occasionally appeared to have clinically significant impacts on survival time. Similar to dogs, the available literature for cats with monoclonal immunoglobulins is sparse. The largest two studies in cats are Mellor et al and Patel et al, with 24 cats with MRD and 16 cats with MM, respectively. Again, we sought to add to the available data on cats with SPE/IF confirmed M-proteins by looking at the same criteria that were evaluated in dogs. Overall, cats with MRDs had a poorer prognosis when compared to dogs, with the exception of B cell chronic lymphocytic leukemia/lymphoma (BCLL) cases. Evidence of bleeding diathesis was not observed in our cat population and the presence of lytic bone lesions was uncommon. Hypocholesterolemia was a negative prognostic indicator for cats with MRDs (excluding BCLL, which was not included in these analyses). The validity of renal azotemia, hypercalcemia, proteinuria, and BJP as prognostic indicators could not be fully assessed in this study, due to a number of factors. Lastly, the addition of visceral organ involvement to the current veterinary MM diagnostic scheme may be warranted and can make categorization of MRDs and diagnosis of MM easier, while still correlating with the clinical behavior of these diseases in cats. The work within this thesis adds to available knowledge of MRD in dogs and cats. We have shown that the lack of hyperproteinemia does not rule out the possibility of an M-protein, especially in cases with suspected MRD. Additionally, running SPE and IF in tandem can capture cases with M-protein production that may be missed with SPE alone. CZE SPE is an acceptable alternative method for dM-protein quantification and can be used when AGE SPE is not available. Finally, we present the largest retrospective analysis of dogs and cats with confirmed monoclonal immunoglobulins to date. Similar to previous works, we found that the course of disease is more aggressive in cats with MM when compared to MM in dogs. Renal disease in dogs and hypocholesterolemia in cats were found to be negative prognostic indicators in our study, but other negative prognostic factors either failed to reach statistical significance or could not be evaluated. We strongly recommend the consideration of visceral organ involvement as an additional or alternative criterion for the diagnosis of MM in dogs and cats, as animals diagnosed with MM with this scheme had disease courses similar to those diagnosed with the current scheme. Further work should examine the frequency of BJP, proteinuria, bone involvement in MM cases without apparent musculoskeletal clinical signs.Item Unknown Influence of early life management strategies on indicators of health and performance in pre-weaned dairy calves and mature cows(Colorado State University. Libraries, 2021) Velasquez Munoz, Ana Karina, author; Pinedo, Pablo, advisor; Lombard, Jason, committee member; Rao, Sangeeta, committee member; Roman Muniz, Ivette Noami, committee memberTo view the abstract, please see the full text of the document.Item Open Access Perianesthesia analgesia, recovery efficacy, and financial impact of ultrasound-guided lumbar plexus and sciatic nerve analgesia in dogs undergoing tibial plateau leveling osteotomy(Colorado State University. Libraries, 2022) Warrit, Kanawee, author; Boscan, Pedro, advisor; Monnet, Eric, advisor; Steffey, Eugene, committee member; Twedt, David, committee member; Rao, Sangeeta, committee member; Fails, Anna Dee, committee memberPerioperative analgesia is critical for patients undergoing surgery because uncontrolled pain can result in deleterious consequences and predispose chronic pain. Therefore, developing an appropriate analgesia technique is crucial, and in this study, an analgesia protocol was investigated in dogs undergoing tibial plateau leveling osteotomy (TPLO). The TPLO is a surgical technique used to stabilize the stifle joint for treating cranial cruciate ligament disease. This surgical procedure is invasive and painful. Therefore, multimodal analgesia is often required for controlling pain associated with TPLO surgery. This study used ultrasound-guided regional anesthesia of the lumbar plexus and sciatic nerve as a component of multimodal analgesia to control perioperative pain compared to patients only receiving a standard systemic analgesia. The study was designed to evaluate the efficacy of regional anesthesia and to determine the financial impact of this additional multimodal procedure. We hypothesized that ultrasound-guided lumbar plexus and sciatic nerve blocks would provide a better analgesic effect intraoperative and postoperatively. The second part of the study we hypothesized that ultrasound-guided lumbar plexus and sciatic nerve blocks would increase the anesthesia cost. It would then be possible to determine a cost – benefit of the procedure. The study was designed as a prospective, randomized, blinded clinical trial. Twenty dogs underwent TPLO surgery were enrolled in the study and randomly assigned to regional analgesia (RA) or control (CON) group. Dogs in the RA group received 0.5% ropivacaine for ultrasound-guided lumbar plexus and sciatic nerve blocks. The total dose of ropivacaine for both blocks was 0.15 mg/kg. Dogs in the CON group received sterile 0.9% saline for the blocks. All dogs received 0.2 mg/kg of hydromorphone and 0.02 mg/kg of atropine for anesthesia premedication. Propofol was administered for anesthesia induction to perform endotracheal tube intubation. Isoflurane in oxygen was delivered using a circle rebreathing system to maintain anesthesia. The ultrasound-guided lumbar plexus and sciatic nerve blocks were performed prior to TPLO surgery. Fentanyl was used for intraoperative as rescue analgesia to reduce the response from surgical stimulation or with an increase in heart rate, respiratory rate, or mean arterial blood pressure. Isoflurane was adjusted to maintain the appropriate anesthesia plane. Hypotension was treated following a stepwise protocol, in a sequencing fashion. The treatment protocol was added until the complications was resolved. The treatment protocol started from decreased isoflurane vaporizer setting, lactate Ringer's solution bolus, hetastarch bolus, and dopamine administration. At extubation, the recovery quality and pain were evaluated. Dexmedetomidine was used to treat poor recovery quality and pain. During the postoperative 12 hours period, pain and recovery quality were assessed by Colorado State University acute pain scale, visual analog pain scale, and modified University of Melbourne pain scale. Fentanyl or methadone was used for postoperative rescue analgesia. Dexmedetomidine or acepromazine was administered to calm the patient. The amount of every drug used, complications management, and extra nursing care were recorded to evaluate the blocks' efficacy. The micro-costing technique was used to collect the financial data and was analyzed to determine the financial impact. In the clinical study, there was a statistically significant difference in the amount of intraoperative fentanyl administered for rescue analgesia between the groups (p = 0.02), with lesser doses given to the RA group. Hypotension was found in 40% of dogs in the RA group and 80% of the dogs in the CON group (p = 0.16). Dogs in the RA group required less intensive treatment than in the CON group. There was a statistically significant difference in the recovery scores between the groups, with those in the RA group having lower recovery scores (p = 0.04). In the postoperative period, the time to receive the first dose of rescue analgesia for dogs in the RA group was longer than dogs in the CON group (p=0.04). Micro-costing method was used for collecting the monetary information. The cost analysis was performed for evaluating the costs of dogs that received ultrasound-guided regional anesthesia with 0.5% ropivacaine and 0.5% sterile saline. The anesthesia fixed cost for the surgery was US$354. There was a statistically significant difference between the variable costs, with the RA group (US$82.65 (69.15-94.56); median (min-max)) having less anesthesia variable costs than dogs in the CON group (US$125.8 (55.23 to 156.35); p = 0.02). The additional cost for a charge per service of the use of ultrasound and electro-nerve stimulator machines (US$26.62) affects the total anesthesia cost for the RA group into both direction, it can enhance and save the total anesthesia cost. It can increases the total anesthesia cost by $US40.54 per dog and it can save the total anesthesia cost by $US35.17 per dog. From the clinical perspective, the number of dogs receiving TPLO surgery at the study hospital is approximately 160 cases per year. This number was used for estimating cost benefit per year performing nerve blocks for TPLO surgery and found that the nerve blocks would potentially increase the total cost for 160 dogs to US$6,486.40 per year but would decrease the total anesthesia cost by US$5,627.20 per year. Ultrasound-guided lumbar plexus and sciatic nerve regional analgesia was found to be an effective multimodal analgesia for TPLO surgery. The technique provided effective intraoperative analgesia that decreased rescue analgesia during surgery and led to better recovery from anesthesia for the dogs in this study. The ultrasound-guided analgesia technique would increase anesthesia costs but better analgesia, anesthesia, and decreased complications provided significant cost-saving benefits when performing regional analgesia for TPLO surgery.Item Unknown Social ecological determinants of occupational zoonotic disease exposure on Colorado dairy farms(Colorado State University. Libraries, 2019) Palomares Velosa, Jairo Enrique, author; Salman, Mo D., advisor; Roman-Muniz, Ivette N., advisor; Rao, Sangeeta, committee member; McConnel, Craig, committee member; Reynolds, Stephen, committee memberThe presence of zoonotic pathogens in dairy farms is a known risk for people that work and live in these settings. People who work or live on a farm, farm visitors, service providers, and veterinarians are the most at risks of zoonotic infections. Dairy cattle operations represent a working environment with a high risk of exposure to zoonotic pathogens. The prevention of zoonotic diseases in animal-human interfaces can be challenging. Due to the complexity of the social ecological system, and it requires comprehensive, integrative, and culturally compelling interventions. It has been demonstrated that the behavior of the person at risk can affect their exposure to infectious agents. As demonstrated in other settings, the implementation of consistent and robust preventive measures can change the behavior of persons at risk and success-fully decrease exposure to risk factors. One of the host factors that affect exposure to human infectious diseases is the behavior of the people at risk. The SEM is a theory-based framework that has been used to scientifically explore the complex and interactive personal and environmental factors that affect people's preventive behaviors in specific settings. In general, the aim of epidemiological studies on infectious diseases using the SEM framework is to inform the development or improvement of comprehensive and compelling intervention strategies that directly target the behavior change process at different levels of influence. In this research, we conducted several research activities using the Social Ecological Model (SEM) approach to expand our understanding of host and environmental factors that affect the exposure of zoonotic diseases as work hazards. In the first research chapter (chapter 2) we proposed an SEM with potential factors affecting the preventive behavior of people at risk of zoonotic diseases in dairy farms. In the next chapter, we use this model to build an instrument that measures SE factors for workers of dairy farms and provide sources of validity for that instrument. And in the last research chapter (chapter 4), we identify that self-efficacy and negative workplace perceptions are risk factors of Salmonella Dublin exposure (OR=1.43 [CI 1.11-2.22] & 1.22 [CI 1.02-1.53] respectively) and that knowledge and positive management perceptions were protective factors (OR = 0.90 [CI 0.79-1.00] & 0.91 [CI 0.82-1.00] respectively). Perception of supervisors and coworkers is a protective factor of Campylobacter exposure (OR=0.89 [CI 0.79-0.98]). Based on our observations, a supporting organizational environment, with supervisors and coworkers as deliverers of accurate safety information, and with increased knowledge and understanding of the potential risks and consequences of zoonotic diseases would help to reduce the occupational exposure of zoonotic disease in these farms.Item Open Access The burden of acute gastrointestinal illness and foodborne illness caused by five major pathogens among nondeployed active duty US Army service members 2014-2015(Colorado State University. Libraries, 2016) Mullaney, Sara Beth, author; Salman, Mo, advisor; Hyatt, Doreene, committee member; McCluskey, Brian, committee member; Rao, Sangeeta, committee memberTo view the abstract, please see the full text of the document.Item Open Access The efficacy of red beetroot juice supplementation to improve cardiometabolic health in middle-aged/older adults with overweight or obesity(Colorado State University. Libraries, 2019) Litwin, Nicole S., author; Johnson, Sarah A., advisor; Pagliassotti, Michael J., committee member; Seals, Douglas R., committee member; Gentile, Christopher L., committee member; Rao, Sangeeta, committee memberCardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed societies worldwide. Advancing age is the primary risk factor for CVD, with lifestyle factors such as diet and nutrition also playing a role. Aging results in adverse changes to the arteries including vascular endothelial dysfunction which is characterized by a decline in nitric oxide (NO)-mediated endothelium-dependent dilation, and increased stiffening of large elastic arteries. This age-associated vascular dysfunction is predominantly driven by increased oxidative stress and chronic inflammation and contributes to the development of CVD through the development of atherosclerotic plaque and hypertension. Previous research suggests that a single high-fat meal may result in transient impairments in postprandial vascular endothelial function, which is thought to be driven by a postprandial pro-inflammatory and oxidative stress response to hypertriglyceridemia and/or hyperglycemia, resulting in a decline in NO bioavailability. This phenomenon may be exaggerated in aging individuals with overweight or obesity, though previous research findings have been inconclusive. Nonetheless, repeated high-fat meal consumption may increase CVD risk through impairments in postprandial vascular endothelial function, thus warranting further investigation. While the mechanisms of postprandial vascular endothelial dysfunction continue to be fully elucidated, an emerging area of research suggests that the oral microbiota may determine steady-state NO levels. Recent scientific discoveries indicate that the oral microbiota reduces dietary inorganic nitrate to nitrite and NO (known as the enterosalivary nitrate-nitrite-NO pathway), thus providing a new therapeutic target for CVD risk management. Red beetroot juice is a rich source of inorganic nitrate as well as other bioactive compounds such as betalains, flavonoids, carotenoids, and ascorbic acid, and previous research suggests that it may improve several parameters of cardiometabolic health including vascular endothelial function. The goals of this dissertation research were to 1) examine the clinical efficacy of acute and chronic red beetroot juice supplementation on postprandial vascular endothelial function after a high-fat meal challenge in middle-aged/older men and postmenopausal women with overweight or obesity, and 2) investigate the underlying mechanisms that contribute to vascular and metabolic responses to the meal challenge and supplementation, including the nitrate-dependent and -independent effects of red beetroot juice. To investigate the aforementioned, we conducted a randomized, double-blind, placebo-controlled, 4-period, crossover, clinical trial. To investigate the nitrate-dependent and -independent effects of red beetroot juice, we used 1) a placebo concentrate devoid of inorganic nitrate or polyphenols, 2) red beetroot juice concentrate, 2) nitrate-depleted red beetroot juice concentrate, and 4) a placebo concentrate with an equivalent dose of inorganic nitrate to that of red beetroot juice. We first examined the impact of acute and chronic red beetroot juice supplementation on postprandial vascular endothelial function and other cardiometabolic responses to a high-fat meal challenge. We found that the high-fat meal led to postprandial alterations in several cardiometabolic parameters but did not impair vascular endothelial function. Significant acute and chronic increases in saliva and plasma NO metabolites were observed following consumption of red beetroot juice and the placebo plus inorganic nitrate, but these increases were not paralleled by significant changes in vascular endothelial function. Although the meal and treatments altered several other parameters of cardiometabolic health, there were no consistent effects of the treatments on those parameters. Next, we examined the relationship between oral nitrate-reducing bacteria and NO metabolites following acute and chronic red beetroot juice supplementation to gain insight on the impact of the oral microbiota on dietary nitrate metabolism and vascular responses to the high-fat meal. We found that red beetroot juice and inorganic nitrate salt supplementation may alter the oral microbiome to favorably affect NO metabolism and vascular endothelial function in this population. Taken together, these results suggest that although red beetroot juice did not modulate postprandial vascular endothelial function, it may be a promising dietary intervention for targeting the enterosalivary nitrate-nitrite-NO pathway to increase NO bioavailability in middle-aged/older adults with overweight or obesity. Further research is needed to evaluate the potential of red beetroot juice as an oral microbiota targeted therapy for improving NO bioavailability and overall cardiovascular health. Additionally, further research is needed to better understand the impact of high-fat meal consumption on cardiometabolic health.