Functional Outcome in Obese Patients Undergoing Image-Based Cruciate Retaining Robotic-Assisted Total Knee Arthroplasty Using the Subvastus Approach: A Short-Term Study.

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.

The AGEs/RAGE Signaling Pathway Regulates NLRP3-Mediated Neuronal Pyroptosis After MCAO Injury in Lepr-/- Obese Rats.

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.

An insight into the updated pharmacotherapy of metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals: a review.

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.

Curcumin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice.

SCOPE: Curcumin (Cur), with diverse pharmacological properties, shows anti-obesity, immunomodulatory, and anti-inflammatory effects. Its role in ulcerative colitis complicated by obesity remains unclear. METHODS AND RESULTS: Here, colitis is induced in obese mice using dextran sulfate sodium (DSS), followed by administration of Cur at a dosage of 100 mg kg-1 for 14 days. Cur effectively alleviates DSS-induced colitis in obese mice, accompanied by an increase in body weight and survival rate, reduction in disease activity index, elongation of the colon, decrease in colonic weight, and improvements in ulcer formation and inflammatory cell infiltration in colonic tissues. Additionally, Cur effectively improves lipid metabolism and the composition of the gut microbiota, and enhances mucosal integrity and boosts anti-oxidative stress capacity in obese mice with colitis. Importantly, Cur is effective in improving the homeostasis of memory T cells in obese mice with colitis. Furthermore, Cur regulates inflammatory cytokines expression and inhibits activation of the JAK2/STAT signaling pathway in colonic tissues of obese mice with colitis. CONCLUSIONS: Cur alleviates colitis in obese mice through a comprehensive mechanism that improves lipid metabolism, modulates gut microbiota composition, enhances mucosal integrity and anti-oxidative stress, balances memory T cell populations, regulates inflammatory cytokines, and suppresses the JAK2/STAT signaling pathway.

Time-course effects of exercise intervention on executive function in adolescents with obesity.

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.

Is lifestyle different in male partners experiencing recurrent pregnancy loss compared to men fathering a live birth?

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.

Impacts of age and BMI on vancomycin model choice in a Bayesian software: Lessons from a very large multi-site retrospective study.

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.

Effect Modification by Obesity on Nonsurgical Periodontal Treatment.

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.

Exploring Public Emotions on Obesity During the COVID-19 Pandemic Using Sentiment Analysis and Topic Modeling: Cross-Sectional Study.

BACKGROUND: Obesity is a chronic, multifactorial, and relapsing disease, affecting people of all ages worldwide, and is directly related to multiple complications. Understanding public attitudes and perceptions toward obesity is essential for developing effective health policies, prevention strategies, and treatment approaches. OBJECTIVE: This study investigated the sentiments of the general public, celebrities, and important organizations regarding obesity using social media data, specifically from Twitter (subsequently rebranded as X). METHODS: The study analyzes a dataset of 53,414 tweets related to obesity posted on Twitter during the COVID-19 pandemic, from April 2019 to December 2022. Sentiment analysis was performed using the XLM-RoBERTa-base model, and topic modeling was conducted using the BERTopic library. RESULTS: The analysis revealed that tweets regarding obesity were predominantly negative. Spikes in Twitter activity correlated with significant political events, such as the exchange of obesity-related comments between US politicians and criticism of the United Kingdom's obesity campaign. Topic modeling identified 243 clusters representing various obesity-related topics, such as childhood obesity; the US President's obesity struggle; COVID-19 vaccinations; the UK government's obesity campaign; body shaming; racism and high obesity rates among Black American people; smoking, substance abuse, and alcohol consumption among people with obesity; environmental risk factors; and surgical treatments. CONCLUSIONS: Twitter serves as a valuable source for understanding obesity-related sentiments and attitudes among the public, celebrities, and influential organizations. Sentiments regarding obesity were predominantly negative. Negative portrayals of obesity by influential politicians and celebrities were shown to contribute to negative public sentiments, which can have adverse effects on public health. It is essential for public figures to be mindful of their impact on public opinion and the potential consequences of their statements.

Oxygen reserve index vs. peripheral oxygen saturation for the prediction of hypoxemia in morbidly obese patients: a prospective observational study.

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.

Saturation Effect of Lipid Accumulation Product (LAP) Index on Spinal Bone Mineral Density: A Population-Based Study.

Lipid accumulation product (LAP) has a positive effect on spinal bone mineral density (BMD). However, once LAP levels exceed 27.26, the rate of spinal BMD increase slow down or even decline. This indicates a biphasic relationship between lipid metabolism and BMD, suggesting potential benefits within a certain range and possible adverse effects beyond that range. This study aimed to investigate the potential association between LAP index and BMD in US adults, as well as to explore the presence of a potential saturation effect in this relationship. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. A multiple stepwise regression model was employed to examine the association between LAP index and total spinal BMD. Additionally, a generalized additive model and a smooth curve fitting algorithm were utilized to examine the relationship, and saturation effect study was conducted to determine the saturation level. The calculation formula of LAP used in the study was: (LAP = (waist circumstances (WC) (cm) - 58) × triglyceride (TG) (mmol/L)) for women, and (LAP = (WC (cm) - 65) × TG (mmol/L)) for men. The study involved a total of 7913 participants aged 20 years or older. Through multiple stepwise regression analysis, it was found that individuals with higher LAP scores exhibited higher total spinal BMD. In both the crude and partially adjusted models, total spinal BMD was significantly higher in the highest LAP quartile (Q4) compared to the lowest LAP quartile (Q1) (P < 0.05). Utilizing a generalized additive model and smooth curve, a nonlinear relationship between LAP and total spinal BMD was observed. Furthermore, the study identified the saturation value of LAP to be 27.26, indicating a saturation effect. This research highlights a nonlinear relationship between LAP and total spinal BMD, along with the presence of a saturation effect.

Impaired Sensitivity to Thyroid Hormones is Associated with Central Obesity in Euthyroid Type 2 Diabetes Mellitus Patients with Overweight and Obesity.

Background: Thyroid hormone levels are associated with the distribution of body components in humans. Objective: This study aimed to investigate the associations between thyroid hormone (TH) levels, central sensitivity to THs, and body composition in overweight and obese patients with euthyroid type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study included 1215 euthyroid T2DM patients (721 men and 494 women) aged 20-80 years. The thyroid hormone sensitivity indices included the thyroid feedback quartile-based index (TFQI), thyrotroph T3 resistance index (TT3RI), thyrotroph T4 resistance index (TT4RI), and thyroid-stimulating hormone index (TSHI). The appendicular fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, and appendicular skeletal muscle mass (ASM) were measured via dual-energy X-ray absorptiometry. Results: The data revealed a greater proportion of subjects with impaired central sensitivity to THs in the obese group. TFQIFT4 and TFQIFT3 levels were positively correlated with the upper limb fat ratio, lower limb fat ratio, gynoid fat ratio, and total fat ratio. TSHI was positively correlated with body mass index (BMI), upper limb fat ratio, lower limb fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, total fat ratio, and appendicular skeletal muscle mass index (ASMI) in women. In men, TSHI was only positively correlated with upper limb fat ratio, lower limb fat ratio, and total fat ratio. Logistic regression analysis indicated that TT3RI and TFQIFT3 were independently and positively associated with central obesity and low muscle mass in overweight and obese men. No significant differences were found among the women. Conclusion: THs central sensitivity is related to the body composition of euthyroid T2DM patients. Specifically, high levels of TT3RI and TFQIFT3 are associated with central obesity and low muscle mass in T2DM men with overweight and obesity.

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Adolescents Without Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have become the leading anti-obesity drugs for adults, and a similar trend may follow in adolescents with its recent approval for this age group. However, there is a lack of comparative analysis on the weight loss effects and safety of GLP-1 RAs in obese or overweight pediatric and adolescent populations, especially those who are non-diabetic. This systematic review and meta-analysis aim to provide current evidence on the efficacy and safety of GLP-1 RAs as an anti-obesity treatment in obese or overweight non-diabetic pediatric and adolescent populations. METHOD:  We searched electronic databases from inception until January 2024 for randomized controlled trials (RCTs) that analyzed the weight loss effect of GLP-1 receptor agonists in adolescents with obesity or overweight without diabetes mellitus. Search results were screened, and eligible studies were included to perform a systematic review and meta-analysis using the Review Manager (RevMan) computer program Version 5.4.1 (The Cochrane Collaboration, 2020) with a random-effects model. The primary efficacy outcomes were changes in body weight, BMI, and BMI Z-score, while the secondary outcomes were the incidence of gastrointestinal adverse events, treatment discontinuation rate due to adverse events, and incidence of serious adverse events. The mean difference, odds ratio, and 95% confidence interval (CI) were used to present the meta-analysis results. Publication bias was visualized using a funnel plot. The quality of the studies was analyzed using Cochrane's Risk of Bias tool (RoB2). RESULTS: A total of seven RCTs with 576 adolescent participants were included in the analysis. GLP-1 RAs significantly achieved greater weight loss than placebo, with a mean difference of -4.98 kg (-8.49, -1.46), I² = 99%, p = 0.006. Subgroup analysis showed that semaglutide had the most pronounced anti-obesity effect (mean difference of -17.70 kg (-18.89, -16.51), p < 0.00001), compared to liraglutide (mean difference of -2.26 kg (-5.17, 0.65), I² = 99%, p = 0.13) and exenatide (mean difference of -3.17 kg (-4.45, -1.90), I² = 0%, p < 0.0001). Similar results were obtained for other efficacy parameters such as BMI and BMI z-score. However, GLP-1 RA was associated with more gastrointestinal adverse events (such as nausea and vomiting) than placebo (3.06 (2.12, 4.42), I² = 0%, p < 0.00001), with incidence comparable among all GLP-1 RAs in the subgroup analysis. The overall risk of bias among included studies was either of 'some concern' or 'high risk.' CONCLUSIONS: Our meta-analysis demonstrated that GLP-1 RAs had a superior anti-obesity effect compared to placebo or lifestyle modification in obese or overweight non-diabetic adolescents, particularly semaglutide, which had a more pronounced anti-obesity effect than liraglutide and exenatide, with tolerable gastrointestinal adverse effects.

Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.

Cholesterol homeostasis is essential for healthy mammalian cells and dysregulation of cholesterol metabolism contributes to the pathogenesis of various diseases including cancer. Cancer cells are dependent on cholesterol. Malignant progression is associated with high cellular demand for cholesterol, and extracellular cholesterol uptake is often elevated in cancer cell to meet its metabolic needs. Tumors take up cholesterol from the blood stream through their vasculature. Breast cancer grows in, and ovarian cancer metastasizes into fatty tissue that provides them with an additional source of cholesterol. High levels of extracellular cholesterol are beneficial for tumors whose cancer cells master the uptake of extracellular cholesterol. In this review we concentrate on cholesterol uptake mechanisms, receptor-mediated endocytosis and macropinocytosis, and how these are utilized and manipulated by cancer cells to overcome their possible intrinsic or pharmacological limitations in cholesterol synthesis. We focus especially on the involvement of lysosomes in cholesterol uptake. Identifying the vulnerabilities of cholesterol metabolism and manipulating them could provide novel efficient therapeutic strategies for treatment of cancers that manifest dependency for extracellular cholesterol.

Short-term HIIT impacts HDL function differently in lean, obese, and diabetic subjects.

Introduction: High density lipoproteins (HDL) exert cardiovascular protection in part through their antioxidant capacity and cholesterol efflux function. Effects of exercise training on HDL function are yet to be well established, while impact on triacylglycerol (TG)-lowering has been often reported. We previously showed that a short-term high-intensity interval training (HIIT) program improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells in insulin-resistant subjects. The purpose of this study is to evaluate HDL function along with changes of lipoproteins after the short-term HIIT program in lean, obese nondiabetic, and obese type 2 diabetic (T2DM) subjects. Methods: All individuals underwent a supervised 15-day program of alternative HIIT for 40 minutes per day. VO2peak was determined before and after this training program. A pre-training fasting blood sample was collected, and the post-training fasting blood sample collection was performed 36 hours after the last exercise session. Results: Blood lipid profile and HDL function were analyzed before and after the HIIT program. Along with improved blood lipid profiles in obese and T2DM subjects, the HIIT program affected circulating apolipoprotein amounts differently. The HIIT program increased HDL-cholesterol levels and improved the cholesterol efflux capacity only in lean subjects. Furthermore, the HIIT program improved the antioxidant capacity of HDL in all subjects. Data from multiple logistic regression analysis showed that changes in HDL antioxidant capacity were inversely associated with changes in atherogenic lipids and changes in HDL-TG content. Discussion: We show that a short-term HIIT program improves aspects of HDL function depending on metabolic contexts, which correlates with improvements in blood lipid profile. Our results demonstrate that TG content in HDL particles may play a negative role in the anti-atherogenic function of HDL.

Increased nuclear receptor subfamily 2, group E, member 1 (NR2E1) concentrations of PBMCs are associated with chronic inflammation in overweight/obesity.

Background: Chronic inflammation plays a crucial role in the pathogenesis of overweight/obesity. Nuclear receptor subfamily 2, group E, member 1 (NR2E1) is one of the nuclear receptor family proteins that play crucial roles in regulating numerous life processes. In this study, we attempted to detect NR2E1 levels in peripheral blood mononuclear cells (PBMCs) of overweight/obese people and preliminarily elucidate the regulatory role of NR2E1 in obesity-related chronic inflammation. Methods: We conducted a cross-sectional analysis of the clinical and biochemical data from 62 overweight/obese people and 70 control subjects. PBMCs of the participants were collected for detection of NR2E1 levels. PBMCs isolated from the control subjects were treated with different concentrations of palmitic acid (PA). We also transfected p-EGFP-N1-NR2E1 plasmids into PBMCs and treated them with PA, then detected TNF-α and IL-6 concentrations in the supernatant of PBMCs. Results: The NR2E1 mRNA and protein levels in overweight/obese people were both significantly higher than those in normal-BMI people (p < 0.01). NR2E1 mRNA levels in PBMCs of overweight/obese people were positively related with TC, FFA, IL-6, TNF-α (r = 0.387, 0.440, 0.610, 0.530, p < 0.01) and LDL-c (r = 0.290, p < 0.05). A similar correlation was also found between NR2E1 protein levels and these parameters. The expression of NR2E1 in PBMCs from the control subjects increased apparently with the treatment of PA in a concentration-depend manner in vitro. Overexpression of NR2E1 in PBMCs decreased TNF-α and IL-6 expression induced by PA (p < 0.01). Conclusion: NR2E1 levels are increased in overweight/obese people and have a positive relationship with TC, FFA, LDL-C, TNF-α and IL-6. Overexpression of NR2E1 could alleviate PA-induced chronic inflammation. NR2E1 may be a potential target for regulating chronic inflammation in obesity.

Maternal dietary practices during pregnancy and obesity of neonates: a machine learning approach towards hierarchical and nested relationships in a Tibet Plateau cohort study.

Studies on obesity and risk factors from a life-course perspective among residents in the Tibet Plateau with recent economic growth and increasing obesity are important and urgently needed. The birth cohort in this area provides a unique opportunity to examine the association between maternal dietary practice and neonatal obesity. The study aims to detect the prevalence of obesity among neonates, associated with maternal diet and other factors, supporting life-course strategies for obesity control. A cohort of pregnant women was enrolled in Tibet Plateau and followed till childbirth. Dietary practice during pregnancy was assessed using the Chinese FFQ - Tibet Plateau version, food items and other variables were associated with the risk for obesity of neonates followed by logistic regression, classification and regression trees (CART) and random forest. Of the total 1226 mother-neonate pairs, 40·5 % were Tibetan and 5·4 % of neonates with obesity. Consuming fruits as a protective factor for obesity of neonates with OR (95 % CI) = 0·61 (0·43, 0·87) from logistic regression; as well as OR = 0·20 (0·12, 0·35) for consuming fruits (≥ weekly) from CART. Removing fruit consumption to avoid overshadowing effects of other factors, the following were influential from CART: maternal education (more than middle school, OR = 0·22 (0·13, 0·37)) and consumption of Tibetan food (daily, OR = 3·44 (2·08, 5·69). Obesity among neonates is prevalent in the study population. Promoting healthy diets during pregnancy and strengthening maternal education should be part of the life-course strategies for obesity control.

Evidence of obesity-induced inflammatory changes in client-owned cats.

Background and Aim: Insulin resistance and type 2 diabetes mellitus are common health issues in obese (OB) cats. In humans, obesity leads to alterations in adipokine and proinflammatory cytokine secretion, causing persistent inflammation. The inflammatory impact of obesity in cats remains unproven. This study investigated associations between obesity and inflammatory and metabolic changes in three groups of client-owned Brazilian domestic shorthair cats: naturally lean, overweight (OW), and OB. Materials and Methods: Cats from the Veterinary Hospital of Professor Sylvio Barbosa e Cardoso (FAVET/UECE) were clinically evaluated. Blood samples were collected for hematological and biochemical profile measurements, and part of the serum was used for measuring adipokine and inflammatory cytokines using sandwich enzyme-linked immunosorbent assay. Results: In both the OW and OB groups, serum cholesterol and insulin concentrations increased, while triglyceride concentrations were notably elevated in the OB group. In the OW and OB groups, serum adiponectin, tumor necrosis factor-α, and interleukin-1ß levels were elevated, and leptin levels were significantly higher in the OB group. Conclusion: This study is the first in Brazil to reveal increased serum levels of inflammatory markers in OW and OB client-owned felines. OW cats exhibited higher proinflammatory marker levels, implying obesity-induced inflammation.

Effect of a Web-Based Nutritional and Physical Activity Intervention With Email Support (the EDDY Program) on Primary School Children's BMI Z-Score During the COVID-19 Pandemic: Intervention Study.

Background: COVID-19 mitigation measures enhanced increases in children's weight and BMI due to decreased physical activity and increased energy intake. Overweight and obesity were major worldwide problems before the pandemic, and COVID-19 increased their severity even more. High BMI directly correlates with health disadvantages including cardiovascular diseases, musculoskeletal disorders, and mental health diseases. Therefore, it is vitally important to develop counteracting interventions to maintain children's health during exceptional situations like pandemics. However, worldwide data from such interventions are limited, and to our knowledge, no suitable study has been carried out during the pandemic in Austria. Objective: This study was conducted to examine a 15-week web-based intervention with email support, the EDDY (Effect of Sports and Diet Trainings to Prevent Obesity and Secondary Diseases and to Influence Young Children's Lifestyle) program and the effect of nutritional education and physical activity on children's BMI z-score during the COVID-19 pandemic in Vienna, Austria. Methods: The intervention consisted of 3 weekly videos-2 physical activity and 1 nutritional education video, respectively-and a biweekly email newsletter for the parents. This study was conducted in a Viennese primary school from February to June 2021 by a team of physicians, nutritionists, and sports scientists, including both professionals and students. The study population included an intervention group (who received web-based nutritional and physical activity training) and a control group (who received no intervention), comprising in total 125 children aged 8 to 11 years. Due to COVID-19 mitigation measures, the control group was a comparative group observed during the prior school year (2019-2020). Anthropometric measurements were obtained before and after the intervention in both groups. Results: Due to a high dropout rate (n=57, 45.6%) because of the mitigation measures, there were 41 children in the intervention group and 27 in the control group. At baseline, the BMI z-score was 1.0 (SD 1.1) in the intervention group and 0.6 (SD 1.2) in the control group (P=.17). After the study period, the BMI z-score decreased by 0.06 (SD 0.21) in the intervention group, whereas it increased by 0.17 (SD 0.34) in the control group (P<.001). Comparing the change in BMI z-scores within BMI categories in the intervention group and control group revealed a statistically significant difference in the normal-weight children (P=.006). Further results showed that the decrease in BMI z-score was significant in the intervention group among both boys (P=.004) and girls (P=.01). Conclusions: A web-based intervention with combined nutritional education and physical activity training might be an adequate tool to lessen the enhanced increase in body weight during a pandemic. Therefore, additional studies with greater sample sizes and different locations are needed. As the implementation of such intervention programs is essential, further studies need to be established rapidly.

The serum uric acid-to-high-density lipoprotein cholesterol ratio is a predictor for all-cause and cardiovascular disease mortality: a cross-sectional study.

Objective: The exact relationship between the serum uric acid-to-HDL cholesterol ratio (UHR) and mortality rates remains enigmatic among American adults. This study aims to clarify the association between UHR and both all-cause and cardiovascular disease (CVD) mortality in US adults. Methods: This study enrolled 48054 patients from the National Health and Nutrition Examination Survey (NHANES). Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31,2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between UHR and mortality. Dose-response relationships were explored using restricted cubic splines, and stratified analyses were conducted based on gender, age, race, education, PIR, smoking status, alcohol intake, physical activity, BMI, diabetes and hypertension. Results: During the follow-up period, the overall mortality for all-cause and CVD was 10.9% and 2.7%, respectively. The adjusted HRs in the highest quintile were 1.16 (95% CI: 1.05, 1.29) for all-cause mortality and 1.2 (95% CI: 1, 1.45) for CVD mortality. In diabetes, obese, and CVD subgroups, significantly elevated adjusted HRs were observed for both all-cause and CVD mortality. Specifically, diabetes patients had adjusted HRs of 1.32 (95% CI: 1.11, 1.57) and 1.38 (95% CI: 1.01, 1.90), obese individuals had HRs of 1.32 (95% CI: 1.10, 1.58) and 1.55 (95% CI: 1.06, 2.28), and CVD patients had HRs of 1.29 (95% CI: 1.10, 1.50) and 1.38 (95% CI: 1.06, 1.79), respectively. A non-linear relationship between UHR and mortality was identified, with critical thresholds of 12.4 for all-cause mortality and 10.7 for CVD mortality in the general population. Significant interactions were observed between UHR and stratified variables, including gender, BMI, education, smoking, alcohol use, and hypertension for all-cause mortality, while significant interactions were observed based on gender, smoking, and alcohol intake for CVD mortality. Comparable trends were also observed in patient with diabetes, obese and CVD. Conclusions: In this cohort study, we provide novel insights into the association between serum UHR concentrations and mortality in the general population. UHR is a strong predictor of all-cause and cardiovascular mortality in the general population.