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1.
BMC Public Health ; 24(1): 3020, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39482632

RESUMO

BACKGROUND: Chronic kidney disease (CKD) and overweight/obesity are significant global public health issues. Appropriate free-time physical activity (PA) is essential for overweight/obese patients with chronic kidney disease, but specific guidelines are lacking. The present study was conducted to determine the association between PA and all-cause mortality in these patients. METHODS: Data from 3,434 overweight/obese adults with CKD from the 1999-2016 National Health and Nutrition Examination Surveys were analyzed. Associations between clinical/laboratory findings and PA intensity (moderate and vigorous) were investigated. The all-cause mortality of patients in different PA categories were compared by Kaplan-Meier analysis. Factors associated with all-cause mortality were determined using a Cox proportional hazards model. A restricted cubic spline was employed to obtain a more flexible and detailed representation of the relationship between PA intensity and all-cause mortality, with better predictive capability. RESULTS: The Kaplan-Meier analysis revealed that greater all-cause mortality was associated with < 10 min/week moderate/vigorous PA (log-rank p < 0.001). A greater survival probability was associated with ≥ 150 min/week vigorous PA or 10-149 min/week moderate PA (log-rank p < 0.001). Age, gender, vigorous PA, smoking status, alcohol consumption, diabetes status, eGFR, serum albumin level, uric acid level, and blood urea nitrogen level were identified as factors associated independently with mortality in the Cox proportional hazards analysis. The restricted cubic splines revealed that these relationships were non-linear (all p < 0.05). Kaplan-Meier analysis of data from patients who engaged in 10-450 min/week moderate/vigorous PA revealed significant differences between the 0-74-min/week and other vigorous PA groups (all log-rank p < 0.001). CONCLUSIONS: Extended durations of vigorous PA are associated with reduced all-cause mortality in overweight/obese patients with CKD. Clinicians should recommend vigorous free-time PA to these patients, and public health interventions should target this goal to maximize patient health.


Assuntos
Exercício Físico , Inquéritos Nutricionais , Obesidade , Sobrepeso , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Obesidade/mortalidade , Obesidade/complicações , Exercício Físico/fisiologia , Estudos Longitudinais , Adulto , Idoso , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia
2.
Cureus ; 16(9): e68430, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39360092

RESUMO

Introduction Knee osteoarthritis (OA) is a prevalent degenerative joint disease that significantly affects quality of life, especially among obese and morbidly obese individuals. Total knee arthroplasty (TKA) is an effective treatment for end-stage OA, but it presents unique challenges in obese patients. The mini-subvastus approach (SA) and robotic-assisted TKA (RA-TKA) are emerging techniques that may address these challenges. This study evaluates the clinical and radiological outcomes of cruciate-retaining (CR) RA-TKA using the mini-subvastus approach in obese and morbidly obese patients. Methods This study included 114 obese patients (215 knees) with primary OA who underwent CR RA-TKA (Maxx Meril CR knee, USA) using the Cuvis Joint® robotic system. Patients had a BMI of ≥30 kg/m² (n=101) and morbid obesity with a BMI ≥40 kg/m² (n=13). Preoperative planning involved CT scans and the J-planner for optimal implant size and positioning. Surgery was performed without tourniquets, and patients were mobilized postoperatively. Clinical outcomes were assessed using visual analog scale (VAS) scores and the American Knee Society Score (AKSS) at three and six months. Results The study included 85 females and 29 males with an average age of 61.8 years. Satisfactory knee exposure was achieved in all cases using SA, with no major complications such as wound infections, deep vein thrombosis, or component misalignment. Intraoperative challenges were managed effectively, including two cases of medial collateral ligament avulsion and one partial patellar tendon avulsion. Postoperative VAS scores showed significant pain reduction from pre-op (6.54) to post-op day 3 (1.3). AKSS improved from a pre-op average of 33.9 to 70.7 at three months and 80.9 at six months. Most patients (80%) achieved exceptional range of motion (ROM) ≥120° at six months. Discussion The mini-subvastus approach in RA-TKA offers several advantages, including reduced postoperative pain, faster recovery, and improved quadriceps strength, even in obese patients. The use of robotic assistance ensures accurate component positioning and alignment, mitigating the challenges typically associated with obese patients undergoing TKA. Conclusion The study demonstrates the feasibility and effectiveness of CR RA-TKA using the mini-subvastus approach in obese and morbidly obese patients. This technique provides adequate exposure, reduces pain, and promotes early mobilization and recovery with satisfactory clinical and radiological outcomes. The findings support the potential for wider adoption of this approach in managing knee OA in obese populations, though further studies with longer follow-up are warranted.

3.
Front Psychol ; 15: 1346896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39380755

RESUMO

Objective: This study was to investigate the developmental characteristics of executive function (EF) in obese adolescents and the time-course effects of a 14-week exercise intervention combining aerobic exercise and resistance training on EF in this population. Methods: The experimental group of 28 obese junior high school students participated in the exercise intervention combining aerobic exercise and resistance training, while the control group of 24 healthy weight junior high school students engaged in the regular recess exercise. EF, including inhibition, working memory, and cognitive flexibility, was assessed 1 week prior to the exercise intervention and at 12 and 14 weeks post-intervention. Changes in EF sub-functions in both groups at different time points during the exercise intervention were analyzed. Results: The findings revealed that obese junior high school students exhibited lower levels of inhibition (p = 0.003, Cohen's d = 0.848) and cognitive flexibility (p = 0.013, Cohen's d = 0.706) compared to their healthy weight peers. The exercise intervention combining aerobic exercise and resistance training led to significant improvements in EF among obese junior high school students, with inhibition (p < 0.01, Cohen's d = 0.713; p = 0.003, Cohen's d = 0.683) and cognitive flexibility (p = 0.001, Cohen's d = 0.797; p < 0.01, Cohen's d = 0.890) showing significant improvement at 12 and 14 weeks post-intervention, and working memory demonstrating significant improvement at 14 weeks (p = 0.004, Cohen's d = 0.710). No significant differences were observed in EF over time in healthy weight junior high school students. Conclusion: Obese adolescents had impaired EF, as evidenced by low levels of the inhibition and cognitive flexibility compared to healthy weight adolescents. The exercise intervention combining aerobic exercise and resistance training had a positive effect on EF of obese adolescents. The time-course effects of the intervention on improvements in inhibition, working memory, and cognitive flexibility varied with intervention duration in obese adolescents, with significant changes in inhibition and cognitive flexibility observed at 12 weeks and significant changes in working memory at 14 weeks.

4.
JDR Clin Trans Res ; : 23800844241276863, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39385374

RESUMO

INTRODUCTION: Obesity is associated with increased periodontal disease prevalence and incidence. This retrospective cohort study examined whether body mass index (BMI) is an effect modifier of periodontal treatment outcomes in patients attending an urban dental school clinic. METHODS: Data were extracted from electronic health records of 344 patients at a large urban dental school clinic who had at least 1 tooth with a probing pocket depth (PD) ≥5 mm at baseline and who subsequently received nonsurgical periodontal treatment. BMI was computed from self-reported weight and height and categorized as obese (≥30 kg/m2), overweight (25-29.9 kg/m2), or healthy (18-24.9 kg/m2). The primary treatment outcome of interest was defined as having no teeth with PD ≥5 mm in a quadrant on follow-up after nonsurgical periodontal therapy. That outcome was considered to represent treatment success in this study. Secondary outcomes included changes in mean PD and clinical attachment loss (CAL). Analyses included 879 treated quadrants among 344 patients (185 males, 159 females; mean age 49 ± 12 y at baseline; mean posttreatment follow-up of 6 ± 2 mo). Clinical outcomes in patients who were overweight or obese were compared to healthy-weight patients using generalized linear models for binary or continuous outcomes, accounting for clustering within patients. Covariates were age, gender, tobacco use, history of diabetes, insurance type, and number of baseline sites ≥5 mm. RESULTS: Obesity was associated with a significantly lower likelihood of successful nonsurgical treatment (odds ratio = 0.47; 95% confidence interval, 0.25-0.88) than healthy weight. Being overweight was not associated with treatment success. Posttreatment reductions in the percentage of sites with pockets ≥5 mm and CAL ≥5 mm were greater in patients with healthy weight as compared to those either overweight or obese. However, posttreatment changes in mean PD and CAL did not differ among the BMI groups. CONCLUSIONS: Obesity adversely modifies the effectiveness of nonsurgical periodontal treatment among dental school clinic patients. KNOWLEDGE TRANSFER STATEMENT: The results of this study may be used by dental providers to better understand and manage periodontal therapy in patients with obesity. Furthermore, patients will be better informed about their therapeutic options and outcome success.

5.
Biochem Biophys Res Commun ; 735: 150800, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39406024

RESUMO

Obesity-mediated hypertension is a worldwide problem. Recent research has indicated that chronic inflammation is associated with the pathogenesis of obese hypertension. Activated immune cells infiltrate target organs, such as arteries, kidneys, and brain, causing end-organ damage and hypertension. Histone deacetylase 6 (HDAC6) regulates the inflammatory cell activity mediating the production of inflammatory cytokines and may play a role in the crosstalk between inflammation and hypertension. In this study, we investigated the roles of HDAC6 in high-fat diet (HFD)-induced kidney inflammation and hypertension. Nine-week-old male C57BL/6 mice were fed either a normal diet (ND) or HFD for 15 weeks. HFD-induced hypertension with increased HDAC6 activities in the kidney and bone marrow-derived macrophages (BMDM). When HFD group reached the hypertensive phase, each group of mice was intraperitoneally injected with vehicle or selective HDAC6 inhibitor Tubacin (1 mg/kg/day) for 14 days. Tubacin treatment lowered blood pressure (BP) of HFD-fed mice to the normal level with successful inhibition of HDAC6 activity. Immunohistochemical staining of F4/80, which is known as a macrophage marker, revealed that HFD promoted macrophage infiltration into the kidney. Consequently, pro-inflammatory factors TNFα and IL-6 gene expressions in the kidney were increased by HFD. Tubacin canceled HFD-induced macrophage infiltration and inflammation in the kidney. HDAC6 gene silencing and Tubacin treatment in Raw 264.7 cells also blocked the chemoattractant-stimulated cell migration in vitro. The results reveal the novel role of HDAC6 in BMDM migration, kidney inflammation, and high BP induced by HFD providing HDAC6 inhibitors as a therapeutic option for obesity-mediated hypertension.

6.
Int J Mol Sci ; 25(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39409093

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, affecting up to 30% of the population, with approximately 20% of cases occurring in non-obese individuals. The recent shift to the term metabolic dysfunction-associated steatosis liver disease (MASLD) highlights the disease's heterogeneity. However, there are no well-established animal models replicating non-obese NAFLD (NO-NAFLD). This study aimed to evaluate the relevance of the high-fat diet (HFD) combined with the propylthiouracil (PTU)-induced rat model in mimicking the histopathology and pathophysiology of NO-NAFLD. We first analyzed metabolic and clinical parameters between NO-NAFLD patients (Average BMI = 21.96 kg/m2) and obese NAFLD patients (Average BMI = 29.7 kg/m2). NO-NAFLD patients exhibited significantly higher levels of carnitines, phospholipids, and triglycerides. In the animal model, we examined serum lipid profiles, liver inflammation, histology, and transcriptomics. Hepatic steatosis in the HFD+PTU model at week 4 was comparable to that of the HFD model at week 8. The HFD+PTU model showed higher levels of carnitines, phospholipids, and triglycerides, supporting its relevance for NO-NAFLD. Additionally, the downregulation of lipid synthesis-related genes indicated differences in lipid accumulation between the two models. Overall, the HFD+PTU-induced rat model is a promising tool for studying the molecular mechanisms of NO-NAFLD.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Hepatopatia Gordurosa não Alcoólica , Propiltiouracila , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Propiltiouracila/efeitos adversos , Propiltiouracila/toxicidade , Ratos , Masculino , Humanos , Dieta Hiperlipídica/efeitos adversos , Feminino , Pessoa de Meia-Idade , Fígado/metabolismo , Fígado/patologia , Obesidade/metabolismo , Obesidade/complicações , Obesidade/induzido quimicamente , Metabolismo dos Lipídeos , Adulto , Triglicerídeos/sangue , Triglicerídeos/metabolismo
7.
Front Endocrinol (Lausanne) ; 15: 1381925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39398340

RESUMO

Background: Obesity among adolescents have become a global public health problem. Exercises can effectively improve the bio-physiological factors of obese adolescents. High-intensive interval training (HIIT) has been applied to obese adolescents. Studies have reported that the Aquatic environment may bring the same or more positive exercise effects as the land environment. Therefore, the purpose of this study was to examine the effects of aquatic and land interventions on selected bio-and physiological variables among obese adolescences. Methods: Twenty-eight obese adolescents who met the requirements participated in and completed this study. The participants were randomly assigned to Aquatic HIIT group (n=17) or Land HIIT group (n=11) for a four-week exercise intervention, 3 time/week. Each Intervention program was one-hour long, including 20 minutes of warm-up, 30 minutes of HIIT and 10 minutes of stretching and relaxation. Bio- and physiological variables including Anthropometry and body composition, Physical Function and blood pressure, and Lipid metabolism indexes were collected before and after the Aquatic and Land interventions. Results: After four weeks of exercise interventions, the body mass, BMI, body fat rate, waist circumference, hip circumference and body water content were significantly reduced (p<0.05), and the lean body mass were significantly increased (p<0.05) in both groups. Both group exhibited significant effects in decreasing, systolic blood pressure (p<0.05), diastolic blood pressure (p<0.01), and increasing vital capacity and total energy consumption (p<0.05). The Aquatic HIIT group showed significant effects on reducing Rest heart rate (p<0.05), but no significant changes in Rest heart rate in Land HIIT group (p=0.364). The low-density lipoprotein cholesterol in both groups was significantly decreased (p<0.05). Moreover, the Aquatic HIIT group had significant better improvements (p<0.05) in lean body mass, waist circumference, waist-to-hip ratio, vital capacity and total energy consumption than Land HIIT group did. Conclusions: The results of the present study demonstrated that in a short-term (4 weeks) both Aquatic and Land HIIT interventions may improve the body composition, physical function, blood pressure and low-density lipoprotein cholesterol (LDL-C) of overweight and obese adolescents. Furthermore, the Aquatic HIIT may be superior than the Land HIIT in weight control among the obese adolescents.


Assuntos
Composição Corporal , Treinamento Intervalado de Alta Intensidade , Humanos , Adolescente , Treinamento Intervalado de Alta Intensidade/métodos , Masculino , Feminino , Obesidade Infantil/terapia , Obesidade Infantil/fisiopatologia , Índice de Massa Corporal , Pressão Sanguínea/fisiologia , Terapia por Exercício/métodos
8.
Nutrients ; 16(19)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39408311

RESUMO

BACKGROUND/OBJECTIVES: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status. METHODS: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively (p < 0.05). RESULTS: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI > 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88-8.52) for the MANO group and 74.59 (95% CI: 13.29-418.68) for the MAO group compared with the MHNO group. CONCLUSIONS: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.


Assuntos
Índice de Massa Corporal , Transplante de Rim , Obesidade , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Transplante de Rim/efeitos adversos , Adulto , Fatores de Risco , Fígado Gorduroso/etiologia , Aspartato Aminotransferases/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Alanina Transaminase/sangue , Transplantados/estatística & dados numéricos , Estudos Transversais
9.
J Pediatr Pharmacol Ther ; 29(5): 550-553, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39411409

RESUMO

Approximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages <18 years who weigh <40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity.

10.
Bioinformation ; 20(8): 862-867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39411758

RESUMO

Hypertension & obesity are important independent predictors of cardiovascular morbidity & mortality specifically left ventricular (LV) functions. With the Objectives to examine the effect of obesity & hypertension on echocardiographic parameters of geometry, systolic, and diastolic functions of left ventricle in asymptomatic adults the cross-sectional study was conducted with 100 individuals (60 male & 40 female). Their Blood Pressure & Body Mass Index was recorded following which they were divided into obese normotensives & non-obese hypertensive. Echocardiographic parameters indicating LV geometry and function were recorded. Data was statistically analysed with Unpaired t test considering p value <0.05 as significant. LV geometry and LV systolic function parameters were significantly altered in non-obese hypertensive. Parameters of LV diastolic functions were affected in obese normotensives. 54% of obese normotensives had LV diastolic dysfunction & 58% of non-obese hypertensive had LV diastolic dysfunction. 2% of obese non-hypertensive individuals had LV systolic dysfunction & 6% of non-obese hypertensive had LV diastolic dysfunction. Hypertension significantly affects LV geometry, LV systolic and diastolic function. Obesity affects LV geometry & diastolic functions of LV even in individuals with preserved systolic function.

11.
Cureus ; 16(9): e69530, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39416581

RESUMO

Infective endocarditis (IE) is a rare but potentially life-threatening condition characterized by inflammation and infection of the inner lining of the cardiac chambers, native or prosthetic valves, or indwelling cardiac devices. In recent decades, its incidence has increased exponentially in healthcare-associated settings such as hemodialysis (HD). The primary causative agent is typically Staphylococcus aureus, followed by streptococci and, in some instances, even fungal infections, although infectious agents do not exclusively cause the condition. In this case report, we detail the clinical presentation of a 46-year-old morbidly obese male with a medical history notable for hypertension, poorly controlled diabetes, and end-stage renal disease necessitating HD. Upon arrival at the emergency department, he presented following a two-week lapse in dialysis sessions, reporting symptoms of altered mental status and lethargy. Shortly after that, the patient's condition rapidly deteriorated, marked by fever, vomiting, and indications of septic shock. Physical examination revealed signs consistent with meningism, alongside the identification of a clotted radio-cephalic fistula, impeding vascular access essential for HD. Furthermore, severe uremia was evident, attributed to the prolonged absence of dialysis treatment. Concurrently, given the patient's presentation of meningeal signs, we were concerned about a potential diagnosis of meningitis. Our immediate priority was to stabilize the patient's vital signs and address the resolution of potential uremic encephalopathy. Additionally, we prioritized the investigation of possible sources of bacterial infection that could be contributing to septic shock and sudden deterioration. This case highlights the complex presentation of IE, which necessitated the collaboration of multidisciplinary teams to address the patient's condition. Additionally, emphasis is placed on HD as a major risk factor for IE, with discussion of associated factors such as constant manipulation of skin flora during dialysis, types of vascular access utilized, and the potential for fistula infection to directly or indirectly contribute to IE. Furthermore, we explore the idea of a possible link between meningism or meningitis and IE.

12.
Farm Hosp ; 2024 Oct 16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39419675

RESUMO

INTRODUCTION: The prevalence of obesity represents a significant global public health challenge, and the available evidence concerning the appropriate dosing of pharmaceutical in patients with obesity is limited. It is uncommon for clinical trials in critically ill patients to include obese individuals, which results in a lack of specific dosing information in product data sheets. The objective of this literature review is to provide clinicians with efficacious and secure guidelines for this cohort of patients. METHODS: A multidisciplinary team comprising pharmacists specialized in hospital pharmacy and physicians with expertise in intensive care medicine was established. The therapeutic groups and, in particular, the most commonly used active ingredients within the Intensive Care Unit were identified and subjected to detailed analysis. The following terms were included in the search: "obese", "overweight", "critical illness", "drug dosification", and "therapeutic dose monitoring". All the information was then evaluated by the working group, which reached a consensus on the dosing recommendations for each drug in obese critically ill patients. RESULTS: A total of 83 drugs belonging to the following therapeutic groups were identified: antivirals, antibacterials, antifungals, immunosuppressants, antiepileptics, vasopressors, anticoagulants, neuromuscular blocking agents and sedatives. A table was produced containing the consensus dosing recommendations for each of the aforementioned drugs following a review of the available evidence. CONCLUSIONS: Drug dosing in obese patients, both in critical and noncritical settings, remains an area with significant uncertainty. This review provides comprehensive and up-to-date information on the dosing of the main therapeutic groups in obese critically ill patients, offering a valuable resource physicians in critical care units and clinical pharmacists in their practice in this setting.

13.
Mol Nutr Food Res ; : e2300672, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420712

RESUMO

SCOPE: The gut microbiota plays a role in fat accumulation and energy homeostasis. Therefore, probiotic supplementation may improve metabolic parameters and control body weight. METHODS AND RESULTS: In this study, mice are fed either a high-fat diet (HFD) or an HFD supplemented with oral gavage of a mixture of three probiotic strains, Bifidobacterium lactis Lafti B94, Lactobacillus plantarum HA-119, and Lactobacillus helveticus Lafti L10 for 7 weeks. It finds that probiotic supplementation modulates body weight gain, food energy efficiency, and fat accumulation caused by the HFD. This probiotic mix prevents liver damage and lipid metabolic disorders in HFD-fed obese mice. The probiotic supplementation significantly downregulates the expression of the proinflammatory cytokines interleukin-1ß, tumor necrosis factor-α, and malondialdehyde (MDA) in the liver and upregulated catalase (CAT), superoxide dismutase (SOD), and nuclear respiratory factor 1 (Nrf1) expression. Mice supplemented with the probiotic mix also show different microbiota compositions, with an increase in Clostridia_UCG-014 and Lachnospiraceae_nk4a136_group and a decrease in the Dubosiella genus compared with those in mice fed only an HFD. Finally, the amounts of fecal pentanoic acid and the three bile acid species increase in mice with probiotic supplementation. CONCLUSION: Treatment with a combination of a mixture of three probiotic strains, B. lactis Lafti B94, L. plantarum HA-119, and L. helveticus Lafti L10 for 7 weeks, ameliorates the effects of HFD induced obesity in mice.

14.
Pharmacotherapy ; 44(10): 794-802, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39382218

RESUMO

BACKGROUND: Model-informed precision dosing (MIPD) optimizes drug doses based on pharmacokinetic (PK) model predictions, necessitating careful selection of models tailored to patient characteristics. This study evaluates the predictive performance of various vancomycin PK models across diverse age and BMI categories, drawing insights from a large multi-site database. METHODS: Adults receiving vancomycin intravenous therapy at United States health systems between January 1, 2022, and December 31, 2023, were included. Patient demographics, vancomycin administration records, and therapeutic drug monitoring levels (TDMs) were collected from the InsightRX database. Age and body mass index (BMI)-based subgroups were formed to assess model performance, with predictions made iteratively. The optimal model for each age-BMI subgroup was chosen based on predefined criteria: models were filtered for mean percentage error (MPE) ≤ 20% and normalized root mean squared error (RMSE) < 8 mg/L, and then the most accurate among them was selected. RESULTS: A total of 384,876 treatment courses across 155 US health systems were analyzed, contributing 841,604 TDMs. Eleven models were compared, showing varying accuracy across age-BMI categories (41%-73%), with higher accuracy observed once TDMs were available for Bayesian estimates of individual PK parameters. Models performed more poorly in younger adults compared to older adults, and the optimal model differed depending on age-BMI categories and prediction methods. Notably, in the a priori period, the Colin model performed best in adults aged 18-64 years across most BMI categories; the Goti/Tong model performed best in the older, non-obese adults; and the Hughes model performed best in many of the obese categories. CONCLUSION: Our study identifies specific vancomycin PK models that demonstrate superior predictions across age-BMI categories in MIPD applications. Our findings underscore the importance of tailored model selection for vancomycin management, especially highlighting the need for improved models in younger adult patients. Further research into the clinical implications of model performance is warranted to enhance patient care outcomes.


Assuntos
Antibacterianos , Teorema de Bayes , Índice de Massa Corporal , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/administração & dosagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Feminino , Masculino , Idoso , Fatores Etários , Adulto Jovem , Monitoramento de Medicamentos/métodos , Software , Modelos Biológicos , Adolescente , Estados Unidos , Idoso de 80 Anos ou mais
15.
Int Arch Allergy Immunol ; : 1-15, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39427653

RESUMO

BACKGROUND: Obese asthma represents a unique phenotype of asthma characterized by severe symptoms, poor medication controls, increased frequency of exacerbations, and an overall diminished quality of life. Numerous factors, including the complex interactions between environment, mechanical processes, inflammatory responses, and metabolites disturbance, contribute to the onset of obese asthma. SUMMARY: Notably, multiple metabolomics studies in the last several years have revealed the significant abnormalities in lipid metabolism among obese asthmatic patients. Several bioactive lipid messengers participate in the development of obese asthma has also been observed. Here, we present and discuss the latest advances regarding how bioactive lipid molecules contribute to the pathogenic process and mechanisms underlying obese asthma. The key roles of potentially significant effector cells and the pathways by which they respond to diverse lipid metabolites are also described. We finally summarize current lipid-related therapeutic options for the treatment of obese asthma and discuss their application prospects. KEY MESSAGES: This review underscores the impacts of abnormal lipid metabolism in the etiopathogenesis of obese asthma and asks for further investigation to elucidate the intricate correlations among lipids, obesity, and asthma.

16.
Hosp Pract (1995) ; : 1-7, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39356238

RESUMO

Metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals represents a distinctive subset of MASH. Current pharmacotherapies, for MASH as demonstrated in clinical trials, predominantly target obese patients with limited consideration for lean MASH. We aimed to systematically review the literature on the pharmacotherapy of lean MASH. We searched standard medical databases, such as PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov to identify eligible studies published in English up to 31 December 2023 regarding the effect of pharmacological interventions in individuals with lean MASH. We have summarized the role of various drug classes including peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, vitamin E, farnesoid X receptor agonists, selective thyroid hormone receptor-ß agonists, and selective cholesterol absorption inhibitors. Consequently, lifestyle interventions, encompassing dietary modifications, exercise, and weight loss particularly directed at visceral obesity or achieving a reduction in body weight are recommended for all non-obese individuals with MASH. A highlight on the only available treatment recommendation for lean MASH is also presented. The available evidence regarding the efficacy of various drugs for the treatment of lean MASH is limited. Conclusive evidence is warranted from clinical trials exclusively involving lean individuals with MASH.

17.
BMC Anesthesiol ; 24(1): 367, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394112

RESUMO

BACKGROUND: Pulse oximetry is a standart of anesthesia for perioperative monitoring. Due to the principles of Hb oxygen dissociation curve, peripheral oxygen saturation has an approximate sensitivity and specificity of 90% for the detection of hypoxemia. OBJECTIVES: The primary outcome of the study was to evaluate ORiⓇ as an early parameter to determine hypoxia in morbidly obese patients. The secondary outcome was to compare the effectiveness of ORiⓇ with SpO2 in non-obese patients. DESIGN: Prospective, observational study. SETTING: Department of elective operating room at tertiary hospital. PATIENTS AND METHODS: Observational study included written informed consent from 51 patients with 19 < BMI < 25 kg/m2 and 51 patients with BMI > 40 kg/m2 undergoing an elective surgery requiring tracheal intubation. In addition to standard monitors, an ORi sensor was placed and baseline values were recorded. The patients were preoxygenated until end tidal expiratory oxygen concentration is reached to 90%. After anesthesia induction and tracheal intubation, the breathing circuit was not connected tracheal tube until the SpO2 decreased to 95%. Shapiro-Wilk, Pearson Chi-square, t-test, and Mann Whitney U test were used for the study. MAIN OUTCOME MEASURES: Times of tolerable apnea, ORiⓇ and SpO2 values at the end of preoxygenation, beginning of intubation, beginning of the ORi alarm, when SpO2 reached 95%, and when ORi reaches a plateau. SAMPLE SIZE: 102 patients. RESULTS: The alert period: time to reach ORiⓇ from 0.24 to a value of 95% SpO2 was observed as 32 s in morbidly obese patients and 94 s in patients with a normal body mass index. The SpO2 alert period was determined as time difference between 97% and 95% SpO2. The data were recorded as 15 s and 36 s, respectively. It was observed that tolerable apnea, ORiⓇ, SpO2 and added alert times were longer in patients with normal BMI compared to morbidly obese patients. CONCLUSIONS: As a result, ORiⓇ can provide an early warning to prevent unexpected hypoxia before saturation begins to decrease in morbidly obese patients. LIMITATIONS: Inability to perform arterial blood gas sampling in the time periods when we looked at the parameters to determine the relationship between ORiⓇ and PaO2. GOV IDENTIFIER: NCT05480748 registered 2022-07-29.


Assuntos
Hipóxia , Obesidade Mórbida , Oximetria , Saturação de Oxigênio , Humanos , Obesidade Mórbida/complicações , Estudos Prospectivos , Feminino , Masculino , Hipóxia/sangue , Pessoa de Meia-Idade , Oximetria/métodos , Saturação de Oxigênio/fisiologia , Adulto , Oxigênio/sangue , Intubação Intratraqueal/métodos , Idoso
18.
Eur J Med Res ; 29(1): 496, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39402650

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) and obesity have become one of the most common chronic diseases, and the global prevalence is increasing year by year. Both are accompanied by hypersensitive C-reactive protein (hs-CRP). At present, there are many predictors of NAFLD. Exploring the relationship between hs-CRP and nonalcoholic fatty liver disease in non-obese people will be helpful for risk prediction and clinical screening in high-risk populations. OBJECTIVE: To explore the relationship between levels of serum hs-CRP and the presence of NAFLD in non-obese people. METHODS: A total of 6558 participants who underwent physical examination from March 2017 to November 2017. Multivariate logistic regression was utilized to analyze the risk factors associated with NAFLD. RESULTS: This study including 4240 males and 2318 females ranging from 20 to 94 years. In 1396 patients with NAFLD, the prevalence rate was 21.3%, among which 1056 (24.9%) males and 340 (14.7%) females had NAFLD. The prevalence of NAFLD was much higher in males compared to females (χ2 = 93.748, P < 0.001). In the nonalcoholic fatty liver group, various factors including hs-CRP, age, WC, BMI, systolic blood pressure and blood pressure diastolic blood pressure were significantly higher than those in the control group. Logistic regression analysis confirmed that hs-CRP was an independent risk factor for NAFLD, even after adjusting for relevant variables. CONCLUSIONS: The prevalence of NAFLD increases with the level of hs-CRP in both men and women who are non-obese. Hs-CRP levels are an important risk factor for nonalcoholic fatty liver disease in non-obese individuals.


Assuntos
Proteína C-Reativa , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Masculino , Feminino , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Idoso , Fatores de Risco , Idoso de 80 Anos ou mais , Adulto Jovem , Prevalência , Obesidade/sangue , Obesidade/complicações , Obesidade/epidemiologia , Biomarcadores/sangue , Índice de Massa Corporal
19.
J Inflamm Res ; 17: 6935-6954, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372588

RESUMO

Background: Obesity is recognized as a primary risk factor for cerebral ischemia, which has shown a significant increase in its incidence among obese patients. The exact mechanism by which obesity exacerbates cerebral ischemic injury is not fully understood though. The present study validated the hypothesis that obesity mediates pyroptosis by the AGEs/RAGE signaling pathway to exacerbate cerebral ischemic injury. Methods: Leptin receptor knockout (Lepr-/- ) rats were used in this study to construct an obesity model, and the middle cerebral artery occlusion (MCAO) models of ischemic stroke were established in Lepr-/- obese rats and their wild-type (WT) littermates respectively. Zea-Longa score, TTC and H&E staining were utilized to evaluate the neurological impairment. Western Blot, immunohistochemistry, and immunofluorescence were used to detect protein expressions. Transmission electron microscopy was used to observe the pores in the neuronal cell membrane in the ischemic penumbra cortex. Results: Compared with WT littermates, Lepr-/- obese rats exhibited exacerbated neuronal injury after MCAO, with higher expressions of NLRP3 inflammasome and pyroptosis-related proteins in the cortical tissue of the penumbra. Moreover, more GSDMD pores were observed on the neuronal cell membranes of Lepr-/- obese rats according to the electron microscopy. Inhibition of NLRP3 inflammasome expression with MCC950 inhibited neuronal pyroptosis after cerebral ischemia in Lepr-/- obese rats, thus reducing neuronal injury. We also found that compared with WT littermates, the levels of AGEs and RAGE in the cortex of Lepr-/- obese rats are significantly higher, with further increase after cerebral ischemia. Inhibition of AGEs/RAGE signaling pathway with FPS-ZM1 reduced the NLRP3 inflammasome-mediated neuronal pyroptosis in Lepr-/- obese rats, thereby mitigating the neuronal damage after cerebral ischemia. Conclusion: The AGEs/RAGE signaling pathway is involved in the exacerbation of cerebral ischemic injury in Lepr-/- obese rats via regulating NLRP3-mediated neuronal pyroptosis.

20.
Andrology ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375297

RESUMO

BACKGROUND: Recurrent pregnancy loss is characterized by three or more consecutive pregnancy losses. Although the causes of recurrent pregnancy loss are often unknown, chromosomal defects and fetal anomalies account for a significant proportion of cases. Previous research has primarily focused on maternal factors, but recent attention has shifted to the role of male lifestyle factors. OBJECTIVES: This study examined how male lifestyle factors and chronic illnesses affect recurrent pregnancy loss in a Danish cohort. Objectives included analyzing demographic and clinical features, as well as assessing lifestyle factors and pregnancy outcomes. MATERIALS AND METHODS: We included 741 males referred to the Danish recurrent pregnancy loss unit between 2009 and 2021, alongside a control group of 1173 males from the PREGCO study. Data on demography, clinical features, lifestyle factors, and pregnancy outcomes were collected and analyzed. RESULTS: The recurrent pregnancy loss group had a higher mean age compared to the controls. Although there was a trend suggesting a higher prevalence of obesity in the recurrent pregnancy loss group, statistical significance was not reached. The prevalence of chronic illnesses was similar in both groups. In the recurrent pregnancy loss group, a higher body mass index and history of previous or current smoking were associated with a lower pregnancy rate, and men who never smoked had an increased likelihood of achieving pregnancy. However, these associations lost significance after adjusting for potential confounders. DISCUSSION: The study suggests an association between male obesity and smoking, and decreased pregnancy rates after referral for recurrent pregnancy loss. However, further research is needed to understand the underlying mechanisms and establish causality in this association. CONCLUSION: The study reveals potential associations between male smoking, male obesity, and reduced pregnancy rates in individuals referred for recurrent pregnancy loss. These findings emphasize the importance of considering male lifestyle factors in the evaluation and management of recurrent pregnancy loss.

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