Peripheral Obesity Research Articles

Incidence and predictors of vascular complications following transcatheter aortic valve implantation: A comparison of the MANTA and suture-based vascular closure devices.

Vascular complications post-transcatheter aortic valve implantation (TAVI) are common. Recent data regarding predictors of vascular complications are limited, particularly comparing newer plug-based devices versus traditional suture-based vascular closure devices (VCD). The primary objective was to identify characteristics that predict a higher risk of vascular complications in TAVI patients, as judged by the VARC-3 criteria, specifically comparing risk factors between suture-based vs MANTA device closure. Retrospective analysis of patients who underwent TAVI between December 2019 and September 2023 was performed. Logistic regression and propensity score matching was performed to ascertain risk factors for vascular complications post-TAVI. Of the 1763 patients, there were 106 vascular complications (6%). There was a nonsignificant increased complication rate in MANTA vs suture-based device closure (8.3% vs 5.3%, p = 0.064). Among these, the most common complications were VCD failure (23%), pseudoaneurysm (20%) and arterial dissection (19%). Obesity (p = 0.021), anemia (p = 0.039) and MANTA device use (p = 0.027) were predictors of vascular complications. Within the MANTA cohort, novel oral anticoagulant (NOAC) use was predictive of vascular complications (p = 0.002). Among suture-based devices, obesity (p = 0.037) and anaemia (p = 0.017) were significant predictors. A propensity matched analysis derived 90 pairs of patients matched for age, gender, diabetes, peripheral arterial disease, NOAC use, anemia and obesity, identifying an average treatment effect of 0.039 (p = 0.04) when MANTA device closure was performed. Vascular complications in TAVI remain common. Identifying predictors such as MANTA device closure, obesity, anemia, and baseline NOAC use will allow for improved risk stratification and appropriate VCD selection in patients undergoing TAVI.

Therapeutic Effects of Capsaicin on Pain Management

Pain is an undesirable sensory experience that occurs from the noisome stimulus, it becomes a warning sign of an upcoming disease or existing disease thereby signaling immediate attention. There exists a variety of pharmacological and non-pharmacological methods to alleviate pain, with their own effects and impacts on health. The natural herb capsicum, used in most families as a spice is also found to have the therapeutic effects of for treating cardiovascular disorders, respiratory issues, gastrointestinal problems, urological disorders, cancer, diabetic peripheral neuropathy, obesity and pain reduction, especially in osteoarthritis and rheumatoid arthritis. It acts as a counter-irritant for various conditions like rheumatism, lumbago and neuralgia. It reduces pain by aiding in the depletion of substance-P and increases the activation of intracellular calcium by activating the calcium channel. The stimulation of transient receptor potential vanilloid 1 (TRPV1) causes effects like analgaesia, anti-infectious, anti-carcinogenic and antioxidant. It is permissible to use capsaicin in low concentrations such as in creams, lotions, gel patches and nasal sprays. High-concentration capsaicin is available in the form of oral formulations, intradermal, subcutaneous and intravenous. Capsaicin is mostly available in topical form, in many concentrations such as 0.025%, 0.0355%, 0.075% and 0.10%. It has been permitted to use capsaicin to the maximum concentration of 8%. Capsaicin is safe to use even in pregnancy, lactation, children and adolescents but is contraindicated for children less than 2 years old as well as for people with bleeding disorders..

Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis.

Obesity is a metabolic and chronic inflammatory disease involving genetic and environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood and immune cell) counts, inflammatory cytokines, and obesity. Summary statistics of 191 gut microbiota traits (N = 18,340), 1,400 plasma metabolite traits (N = 8,299), 128 peripheral cell counts (blood cells, N = 408,112; immune cells, N = 3,757), 41 inflammatory cytokine traits (N = 8,293), and 6 obesity traits were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio methods. Several sensitivity analyses were also utilized to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from gut microbiota to obesity mediated by plasma metabolites, peripheral cells, and inflammatory cytokines. MR revealed a causal effect of 44 gut microbiota taxa, 281 plasma metabolites, 27 peripheral cells, and 8 inflammatory cytokines on obesity. Among them, five shared causal gut microbiota taxa belonged to the phylum Actinobacteria, order Bifidobacteriales, family Bifidobacteriaceae, genus Lachnospiraceae UCG008, and species Eubacterium nodatum group. Furthermore, we screened 42 shared causal metabolites, 7 shared causal peripheral cells, and 1 shared causal inflammatory cytokine. Based on known causal metabolites, we observed that the metabolic pathways of D-arginine, D-ornithine, linoleic acid, and glycerophospholipid metabolism were closely related to obesity. Finally, mediation analysis revealed 20 mediation relationships, including the causal pathway from gut microbiota to obesity, mediated by 17 metabolites, 2 peripheral cells, and 1 inflammatory cytokine. Sensitivity analysis represented no heterogeneity or pleiotropy in this study. Our findings support a causal relationship among gut microbiota, plasma metabolites, peripheral cells, inflammatory cytokines, and obesity. These biomarkers provide new insights into the mechanisms underlying obesity and contribute to its prevention, diagnosis, and treatment.

Association of Prediabetes and Recurrent Stroke in Atrial Fibrillation Patients: A Population-Based Analysis of Hospitalizations and Outcomes.

Prediabetes is a risk factor for ischemic stroke in atrial fibrillation (AF) patients, yet, its impact on recurrent stroke in AF patients remains understudied. Using the 2018 National Inpatient Sample, we investigated the link between Prediabetes and recurrent stroke in AF patients with prior stroke or transient ischemic attack (TIA). Among 18,905 non-diabetic AF patients, 480 (2.5%) had prediabetes. The prediabetic group, with a median age of 78, exhibited a two-fold higher risk of recurrent stroke compared to the non-prediabetic cohort (median age 82), as evidenced by both unadjusted (OR 2.14, 95% CI 1.72-2.66) and adjusted (adjusted for socio-demographics/comorbidities, OR 2.09, 95% CI 1.65-2.64, p < 0.001). The prediabetes cohort, comprising more male and Black patients, demonstrated associations with higher Medicaid enrollment, admissions from certain regions, and higher rates of hyperlipidemia, smoking, peripheral vascular disease, obesity, and chronic obstructive pulmonary disease (all p < 0.05). Despite higher rates of home health care and increased hospital costs in the prediabetes group, the adjusted odds of all-cause mortality were not statistically significant (OR 0.55, 95% CI 0.19-1.56, p = 0.260). The findings of this study suggest that clinicians should be vigilant in managing prediabetes in AF patients, and strategies to prevent recurrent stroke in this high-risk population should be considered.

Neuroinflammation in Obese Children.

Obesity is associated with chronic persistent inflammation due to a pool of tissue macrophages that can penetrate the blood-brain barrier and cause neuroinflammation. The analysis of the association of CD14+CD163+ monocytes in the peripheral blood with cognitive functions in 56 obese children (mean age 11.95 (9.45; 14.45) years) was carried out. The control group consisted of 10 children (mean age 10.4 (9.3; 13.8) years). Standard deviation of the body mass index (SDS BMI) and height (SDS height) were calculated using WHO AnthroPlus software (for children of 6-19 years). Body composition was assessed using bioimpedance measurement. Mononuclear cells were isolated from whole blood by centrifugation on a Ficoll-Urografin density gradient (ρ=1.077 g/ml). The content of CD14+CD163+ monocytes in the peripheral blood was assessed by flow cytometry. To analyze cognitive functions, the intelligence coefficient (IQ) was calculated and a Russian adaptation of the Rey test was performed. We found an increase in the number of M2-polarized CD14+CD163+ monocytes in the peripheral blood with an increase in the obesity degree and in the presence of cognitive decline, as well as a negative correlation of the level of M2-polarized monocytes and IQ, taking into account the excess of visceral fat. The revealed data on the relationship of M2-polarized CD14+CD163+ peripheral blood monocytes with obesity in children and the development of neuropsychological deficiency confirm the role of peripheral visceral obesity and neuroinflammation.

Abstract 15832: Racial Differences in the Utilization and Outcomes of Transcatheter Aortic Valve Replacement

Introduction: The use of transcatheter aortic valvular replacement (TAVR) improves outcomes in patients with aortic stenosis (AS). However, there is limited data describing racial disparities in TAVR use. Our aim was to evaluate outcomes according to racial groups and TAVR use in the national inpatient sample (NIS). Methods: We identified all patients undergoing TAVR between 2016 - 2020 from the NIS of the Health Care Utilization Project database. Patients were classified according to ethnic groups as white, black, Hispanic, and Asians. Outcomes included TAVR utilization by ethnic group, mortality, respiratory failure rates, cardiogenic shock, cardiac arrest, and hospital length of stay (H-LOS). Multivariate analysis was performed adjusting for age, sex, cardiovascular comorbidities, and socioeconomic status. Results: From 296,740 patients who underwent TAVR, 89.5% were white, 4.24% were black, 4.9% were Hispanic, and 1.39% were Asian. Blacks had higher rates of CHF, chronic kidney disease, peripheral vascular disease, obesity, and anemia but lower rates of myocardial infarction, CABG, pacemaker placement and PCI. Hispanic patients showed higher rates of AKI, while Asian patients had higher rates of DM. Blacks had lower adjusted mortality rates compared to whites (aOR: 0.56; CI 0.35 - 0.88 p=0.014). Respiratory failure rates (aOR: 0.82; CI 0.68 - 0.98, p=0.031) and H-LOS (5.2 days vs 3.7 days) were higher in black patients. Whites had a steeper increase in TAVR use compared to other groups during the study period. Patients with AS undergoing TAVR had significant lower adjusted mortality (aOR: 0.95; CI 0.92 - 0.98 p=0.005). Conclusion: White patients are most likely to receive TAVR compared to other ethnic groups. Such differences in TAVR utilization by ethnic group should be studied further to decrease healthcare disparities

Dyspnea-Related Ticagrelor Discontinuation After Percutaneous Coronary Intervention

BackgroundNearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases. ObjectivesThe authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI). MethodsIn the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables. ResultsThe incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566). ConclusionsIn the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

Obesity: a gender-view.

There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective. A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed. The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender-dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements. Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.

Exploring the impact of ketogenic diet on multiple sclerosis: obesity, anxiety, depression, and the glutamate system.

Multiple sclerosis (MS) is a neurodegenerative disorder. Individuals with MS frequently present symptoms such as functional disability, obesity, and anxiety and depression. Axonal demyelination can be observed and implies alterations in mitochondrial activity and increased inflammation associated with disruptions in glutamate neurotransmitter activity. In this context, the ketogenic diet (KD), which promotes the production of ketone bodies in the blood [mainly β-hydroxybutyrate (βHB)], is a non-pharmacological therapeutic alternative that has shown promising results in peripheral obesity reduction and central inflammation reduction. However, the association of this type of diet with emotional symptoms through the modulation of glutamate activity in MS individuals remains unknown. To provide an update on the topic and discuss the potential impact of KD on anxiety and depression through the modulation of glutamate activity in subjects with MS. The main findings suggest that the KD, as a source of ketone bodies in the blood, improves glutamate activity by reducing obesity, which is associated with insulin resistance and dyslipidemia, promoting central inflammation (particularly through an increase in interleukins IL-1β, IL-6, and IL-17). This improvement would imply a decrease in extrasynaptic glutamate activity, which has been linked to functional disability and the presence of emotional disorders such as anxiety and depression.

Small airway dysfunction and obesity in asthmatic patients: a dangerous liaison?

Asthma is a chronic condition characterized by inflammation throughout the entire bronchial airways. Recent findings suggest that ventilation inhomogeneity and small airway dysfunction (SAD) play a particularly significant role in asthma development and clinical manifestations. Obesity is a considerable risk factor for asthma development and morbidity in children and adults. A growing body of evidence suggests that SAD is linked to more severe asthma and poor asthma control in obese patients. However, the knowledge about the relationship between peripheral airway compromise and obesity in asthma is limited, mainly because of the historical lack of access to non-invasive assessment methods for studying SAD. Conventional lung function measurements, like spirometry, cannot accurately assess small airway function. However, in recent years, new specialized tests available in outpatient settings have been found to distinguish SAD from large airway obstruction more accurately compared to spirometry. Therefore, understanding the degree of peripheral airway implication in the underlying pathology is critical for effective asthma control and therapeutic decisions. This review highlights recent findings on the impact of SAD on asthma patients who are obese. Additionally, it explores how new diagnostic methods, such as impulse oscillometry (IOS), may be used in outpatient settings to detect small airway impairment in obese asthma at an early stage, potentially leading to improved asthma treatment.

Intimal CD31-Positive Relative Surfaces Are Associated with Systemic Inflammatory Markers and Maturation of Arteriovenous Fistula in Dialysis Patients.

Arteriovenous fistula dysfunction is a widely disputed subject in the scientific literature on end-stage kidney disease (ESKD). The main cause of mortality and morbidity in these patients is the non-maturation or dysfunction of the arteriovenous fistula. Despite the many complications, the native arteriovenous fistula remains the gold standard in the treatment of these patients requiring renal replacement. This study aims to discuss the predictive role of some systemic inflammatory biomarkers (NLR, PLR, SII, IL-6), intimal hyperplasia, and neoangiogenesis (characterized by intimal-media CD31-positive relative surface) in arteriovenous fistula maturation failure. The present study was designed as an observational, analytical, and prospective study which included patients diagnosed with ESKD with indications of radio-cephalic arteriovenous fistula (RCAVF). Demographic data, comorbidities, preoperative laboratory data and histological/digital morphometry analysis results were processed. The patients included were divided into two groups based on their AVF maturation status at 8 weeks: "Maturation" (Group 1) and "Failed Maturation" (Group 2). There was no difference in the demographic data. In terms of comorbidities, the second group had a greater incidence of heart failure (p = 0.03), diabetes (p = 0.04), peripheral artery disease (p = 0.002), and obesity (p = 0.01). Additionally, regarding the laboratory findings, these patients had higher levels of serum uric acid (p = 0.0005), phosphates (p < 0.0001), and creatinine (p = 0.02), as well as lower levels of total calcium (p = 0.0002), monocytes (p = 0.008), and lymphocytes (p < 0.0001). Moreover, all inflammatory markers (p = 0.001; p < 0.0001; p = 0.006, and p = 0.03) and Ca-P product (p < 0.0001) had higher baseline values in Group 2. Upon immunohistochemical analysis, regarding the density of neoformed vessels, there was a higher incidence of CD31-positive surfaces (p = 0.006) and CD31-positive relative surfaces (p = 0.001); the NLR (r = 0.323; p = 0.03), PLR (r = 0.381; p = 0.04), SII (r = 0.376; p = 0.03), and IL-6 (r = 0.611; p < 0.001) are all significantly correlated with vascular density, as evidenced by CD31. Heart failure, peripheral artery disease, obesity, and diabetes, as well as the systemic inflammatory markers (NLR, PLR, SII, IL-6), intimal hyperplasia, and CD31-positive relative surfaces are predictors of arteriovenous fistula maturation failures.

Disease Characteristic of Obese Patients with Seek Treatment at RSUD Dr. H. Chasan Boesoirie Ternate

Obesity is the accumulation of excess fat due to an imbalance in energy intake with the energy used by the body. Obesity can be differentiated based on the distribution of fat into 2, namely central obesity, which is also called "apple shape obesity" or "android obesity", which is more often found in men, and peripheral obesity which is also called "gynecoid obesity" or "peer shape obesity", which is more often found in women. Some of the risk factors for obesity such as genetics, socioeconomic status, environment, and psychology.&#x0D; This study aims to determine the characteristics of obese patients who seek treatment at RSUD Dr. H. Chasan Boesoirie Ternate in 2019. This study used a descriptive design with a cross-sectional method with a total sample was 95 medical record data for obese patients. This study used secondary data from medical records of obese patients at RSUD Dr. H. Chasan Boesoirie Ternate in 2019.&#x0D; Characteristics of diseases in obese patients at RSUD Dr. H. Chasan Boesoirie Ternate in 2019 were found to be 20-60 years 75 people (80%), women 69 people (72.6%), work as housewives 54 people (56.8%), the level of high school education was 36 people (37.9%), obesity I 68 people (71.6%), and the type of type 2 diabetes mellitus 46 people (48.4%).&#x0D; The highest distribution of obese people was found the most in female, the age group of 20-60 years, and the most comorbidity in diabetes mellitus.&#x0D;

The association between pulmonary artery enlargement and mortality in an Emergency Department population undergoing computed tomography pulmonary angiography.

Findings of an enlarged pulmonary artery diameter (PAd) and increased pulmonary artery to ascending aorta ratio (PA:AA) on contrast-enhanced computed tomography pulmonary angiography (CTPA) are associated with increased mortality in particular groups of patients with cardiopulmonary disease. However, the frequency and prognostic significance of these incidental findings has not been studied in unselected patients evaluated in the Emergency Department (ED). This study aims to determine the prevalence and associated prognosis of enlarged pulmonary artery measurements in an ED cohort. We measured PA and AA diameters on 990 CTPA studies performed in the ED. An enlarged PA diameter was defined as >27 mm in females and >29 mm in males, while an increased PA:AA was defined as >0.9. Poisson regression was performed to calculate prevalence ratios for relevant comorbidities, and multivariable Cox regression was performed to calculate hazard ratios (HR) for mortality of patients with enlarged pulmonary artery measurements. An enlarged PAd was observed in 27.9% of 990 patients and was more commonly observed in older patients and in patients with obesity or heart failure. Conversely, PA:AA was increased in 34.2% of subjects, and was more common in younger patients and those with peripheral vascular disease or obesity. After controlling for age, sex, and comorbidities, both enlarged PAd (HR 1.29, 95% CI 1.00-1.68, p = 0.05) and PA:AA (HR 1.70, 95% CI 1.31-2.22 p < 0.01) were independently associated with mortality. In sum, enlarged PAd and increased PA:AA are common in patients undergoing CTPAs in the ED setting and both are independently associated with mortality.

Adipose Tissue in Peripheral Obesity as an Assessment Factor for Pressure Ulcers.

Scope and Significance: Pressure ulcers are very difficult to treat and pose an economic burden, just below cancer and cardiovascular illness, at 4.82 billion U.S. dollars. It is important to understand the pathophysiology of the condition, risk stratification, and ways of preventing it. Prevention forms the most important aspect of their management. The authors systematically evaluated the existing risk prediction scales and explored the evidence from literature regarding the role of additional factors including body mass index, obesity, subcutaneous tissue thickness, and skin integrity in pressure ulcers. With this review it is hoped that the future management of pressure ulcers will concentrate on the preventable and alterable factors in its pathophysiology. Translational Relevance: The review focuses on how adipose tissue thickness can predict the occurrence of pressure ulcer. If adequately proved that a definite thickness of peripheral adipose tissue is efficient in prevention of pressure ulcers, then methods of maintaining the thickness of this tissue will be the next effective strategy in the management of this chronic issue. Clinical Relevance: The review addresses the management of pressure ulcers to wound care providers and emphasize on confounding parameters of obesity, subcutaneous tissue thickness, and skin integrity during the treatment regimen of pressure ulcers. Objectives: The main objective of this review is to draw a consensus concerning the role of adipose tissue in pressure ulcers, based on the published research. A review of the various preexisting predictive scales for pressure ulcers is a secondary objective to highlight the shortcomings in ulcer management. This review finally aims in the future at paving a way to refine our prognosticating scales for pressure sores based on these results. Accurate preventative injury risk scales are needed so that preventative resources can be directed to the patients for whom they are the most appropriate.

Diabetic foot ulcers: Classification, risk factors and management.

Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection, amputation, and death, and is affecting increasing numbers of patients with diabetes mellitus. The pathogenesis of foot ulcers is complex, and different factors play major roles in different stages. The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate, which means that management and nursing plans need to be considered carefully. The importance of establishment of measures for prevention and management of DFU has been emphasized. Therefore, a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management. In the first part of this review, we list several commonly used classification systems and describe their application conditions, scope, strengths, and limitations; in the second part, we briefly introduce the common risk factors for DFU, such as neuropathy, peripheral artery disease, foot deformities, diabetes complications, and obesity. Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management; in the last part, we emphasize the importance of preventive education, characterize several of the most frequently used management approaches, including glycemic control, exercise, offloading, and infection control, and call for taking into account and weighing the quality of life during the formulation of treatment plans. Multidisciplinary intervention and management of diabetic foot ulcers (DFUs) based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs, and improve their prognosis.

A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice.

Obesity is a chronic peripheral inflammation condition that is strongly correlated with neurodegenerative diseases and associated with exposure to environmental chemicals. The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor activated by environmental chemical, such as dioxins, and also is a regulator of inflammation through interacting with nuclear factor (NF)-κB. In this study, we evaluated the anti-obesity and anti-inflammatory activity of HBU651, a novel AhR antagonist. In BV2 microglia cells, HBU651 successfully inhibited lipopolysaccharide (LPS)-mediated nuclear localization of NF-κB and production of NF-κB-dependent proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also restored LPS-induced mitochondrial dysfunction. While mice being fed a high-fat diet (HFD) induced peripheral and central inflammation and obesity, HBU651 alleviated HFD-induced obesity, insulin resistance, glucose intolerance, dyslipidemia, and liver enzyme activity, without hepatic and renal damage. HBU651 ameliorated the production of inflammatory cytokines and chemokines, proinflammatory Ly6chigh monocytes, and macrophage infiltration in the blood, liver, and adipose tissue. HBU651 also decreased microglial activation in the arcuate nucleus in the hypothalamus. These findings suggest that HBU651 may be a potential candidate for the treatment of obesity-related metabolic diseases.

Ultrasound-Guided Access Reduces Vascular Complications in Patients Undergoing Catheter Ablation for Cardiac Arrhythmias.

Femoral vascular access using the standard anatomic landmark-guided method is often limited by peripheral artery disease and obesity. We investigated the effect of ultrasound-guided vascular puncture (UGVP) on the rate of vascular complications in patients undergoing catheter ablation for atrial or ventricular arrhythmias. The data of 479 patients (59% male, mean age 68 years ± 11 years) undergoing catheter ablation for left atrial (n = 426; 89%), right atrial (n = 28; 6%) or ventricular arrhythmias (n = 28; 6%) were analyzed. All patients were on uninterrupted oral anticoagulants and heparin was administered intravenously during the procedure. Femoral access complications were compared between patients undergoing UGVP (n = 320; 67%) and patients undergoing a conventional approach (n = 159; 33%). Complication rates were also compared between patients with a BMI of &gt;30 kg/m2 (n = 136) and patients with a BMI &lt; 30 kg/m2 (n = 343). Total vascular access complications including mild hematomas were n = 37 (7.7%). In the conventional group n = 17 (10.7%) and in the ultrasound (US) group n = 20 (6.3%) total vascular access complications occurred (OR 0.557, 95% CI 0.283-1.096). UGVP significantly reduced the risk of hematoma &gt; 5 cm (OR 0.382, 95% CI 0.148, 0.988) or pseudoaneurysm (OR 0.160, 95% CI 0.032, 0.804). There was no significant difference between the groups regarding retroperitoneal hematomas or AV fistulas (p &gt; 0.05). In patients with BMI &gt; 30 kg/m2, UGVP led to a highly relevant reduction in the risk of total vascular access complications (OR 0.138, 95% CI 0.027, 0.659), hematomas &gt; 5 cm (OR 0.051, 95% CI 0.000, 0.466) and pseudoaneurysms (OR 0.051, 95% CI 0.000, 0.466). UGVP significantly reduces vascular access complications. Patients with a BMI &gt; 30 kg/m2 seem to particularly profit from a UGVP approach.

Temporal trends of arrhythmias at delivery hospitalizations in the United States: Analysis from the National Inpatient Sample, 2009-2019.

Cardiac arrhythmias are associated with increased maternal morbidity. There are limited data on trends of arrhythmias among women hospitalized for delivery. We used the National Inpatient Sample (NIS) database to identify delivery hospitalizations for individuals aged 18-49 years between 2009 to 2019 and utilized coding data from the 9th and 10th editions of the International Classification of Diseases to identify supraventricular tachycardias (SVT), atrial fibrillation (AF), atrial flutter, ventricular tachycardia (VT), and ventricular fibrillation (VF). Arrhythmia trends were analyzed by age, race-ethnicity, hospital setting, and hospital geographic regions. Multivariable logistic regression was used to evaluate the association of demographic, clinical, and socioeconomic characteristics with arrhythmias. Among 41,576,442 delivery hospitalizations, the most common arrhythmia was SVT (53%), followed by AF (31%) and VT (13%). The prevalence of arrhythmia among delivery hospitalizations increased between 2009 and 2019. Age > 35 years and Black race were associated with a higher arrhythmia burden. Factors associated with an increased risk of arrhythmias included valvular disease (OR: 12.77; 95% C1:1.98-13.61), heart failure (OR:7.13; 95% CI: 6.49-7.83), prior myocardial infarction (OR: 5.41, 95% CI: 4.01-7.30), peripheral vascular disease (OR: 3.19, 95% CI: 2.51-4.06), hypertension (OR: 2.18; 95% CI: 2.07-2.28), and obesity (OR 1.69; 95% CI: 1.63-1.76). Delivery hospitalizations complicated by arrhythmias compared with those with no arrhythmias had a higher proportion of all-cause in-hospital mortality (0.95% vs. 0.01%), cardiogenic shock (0.48% vs. 0.00%), preeclampsia (6.96% vs. 3.58%), and preterm labor (2.95% vs. 2.41%) (all p < 0.0001). Pregnant individuals with age > 35 years, obesity, hypertension, valvular heart disease, or severe pulmonary disease are more likely to have an arrhythmia history or an arrhythmia during a delivery hospitalization. Delivery hospitalizations with a history of arrhythmia are more likely to be complicated by all-cause in-hospital mortality, cardiovascular, and adverse pregnancy outcomes (APOs). These data highlight the increased risk associated with pregnancies among individuals with arrhythmias.

A PDK-1 allosteric agonist improves spatial learning and memory in a βAPP/PS-1 transgenic mouse-high fat diet intervention model of Alzheimer's disease

Diabetes mellitus (DM), peripheral insulin resistance (IR) and obesity are clear risk factors for Alzheimer's disease. Several anti-diabetic drugs and insulin have been tested in rodents and humans with MCI or AD, yielding promising but inconclusive results. The PDK-1/Akt axis, essential to the action of insulin, has not however been pharmacologically interrogated to a similar degree. Our previous cell culture and in vitro studies point to such an approach. Double transgenic APPsw/PSENdE9 mice, a model for Alzheimer's disease, were used to test the oral administration of PS48, a PDK-1 agonist, on preventing the expected decline in learning and memory in the Morris Water Maze (MWM). Mice were raised on either standard (SD) or high fat (HFD) diets, dosed beginning 10 months age and tested at an advanced age of 14 months.PS48 had positive effects on learning the spatial location of a hidden platform in the TG animals, on either SD or HFD, compared to vehicle diet and WT animals. On several measures of spatial memory following successful acquisition (probe trials), the drug also proved significantly beneficial to animals on either diet. The PS48 treatment-effect size was more pronounced in the TG animals on HFD compared to on SD in several of the probe measures. HFD produced some of the intended metabolic effects of weight gain and hyperglycemia, as well as accelerating cognitive impairment in the TG animals. PS48 was found to have added value in modestly reducing body weights and improving OGTT responses in TG groups although results were not definitive. PS48 was well tolerated without obvious clinical signs or symptoms and did not itself affect longevity. These results recommend a larger preclinical study before human trial.

Time-restricted feeding mitigates obesity through adipocyte thermogenesis.

Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. We found that genetic enhancement of adipocyte thermogenesis through ablation of the zinc finger protein 423 (ZFP423) attenuated obesity caused by consumption of a high-fat diet during the inactive (light) period by increasing futile creatine cycling in mice. Circadian control of adipocyte creatine metabolism underlies the timing of diet-induced thermogenesis, and enhancement of adipocyte circadian rhythms through overexpression of the clock activator brain and muscle Arnt-like protein-1 (BMAL1) ameliorated metabolic complications during diet-induced obesity. These findings uncover rhythmic creatine-mediated thermogenesis as an essential mechanism that drives metabolic benefits during time-restricted feeding.