Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety.

Potent incretin-based therapy shows promise for the treatment of obesity along with reduced incidence of cardiovascular events in patients with preexisting cardiovascular disease and obesity. This study assessed the efficacy and safety of the incretin-based obesity treatments, once-weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg, in people with obesity without diabetes. Of the 744 records identified, seven randomized controlled trials (n = 5140) were included. Five studies (n = 3288) investigated semaglutide and two studies (n = 1852) investigated tirzepatide. The treatment effect, shown as placebo-subtracted difference, on body weight was -15.0% (95% CI, -17.8 to -12.2) with -12.9% (95% CI, -14.7 to -11.1) for semaglutide and -19.2% (95% CI, -22.2 to -16.2) for tirzepatide. The treatment effect on waist circumference was -11.4 cm (95% CI, -13.7 to -9.2) with -9.7 cm (95% CI, -10.8 to -8.5) for semaglutide and -14.6 cm (95% CI, -15.8 to -13.4) for tirzepatide. The adverse events related to semaglutide and tirzepatide were primarily of mild-to-moderate severity and mostly gastrointestinal, which was more frequent during the dose-titration period and leveled off during the treatment period. This emphasizes that once-weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg induce large reductions in body weight and waist circumference and are generally well-tolerated.

Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors.

INTRODUCTION: In bipolar women who took lithium during pregnancy, several epidemiology studies have reported small increases in a rare fetal cardiac defect termed Ebstein's anomaly. METHODS: Behavioral, environmental, and lifestyle-associated risk factors associated with bipolar disorder and health insurance status were determined from an Internet search. The search was conducted from October 1, 2023, through October 14, 2023. The search terms employed included the following: bipolar, bipolar disorder, mood disorders, pregnancy, congenital heart defects, Ebstein's anomaly, diabetes, hypertension, Medicaid, Medicaid patients, alcohol use, cigarette smoking, marijuana, cocaine, methamphetamine, narcotics, nutrition, diet, obesity, body mass index, environment, environmental exposures, poverty, socioeconomic status, divorce, unemployment, and income. No quotes, special fields, truncations, etc., were used in the searches. No filters of any kind were used in the searches. RESULTS: Women who remain on lithium in the United States throughout their pregnancy are likely to be experiencing mania symptoms and/or suicidal ideation refractory to other drugs. Pregnant women administered the highest doses of lithium salts would be expected to have been insufficiently responsive to lower doses. Any small increases in the retrospectively determined risk of fetal cardiac anomalies in bipolar women taking lithium salts cannot be disentangled from potential developmental effects resulting from very high rates of cigarette smoking, poor diet, alcohol abuse, ingestion of illegal drugs like cocaine or opioids, marijuana smoking, obesity, and poverty. CONCLUSIONS: The small risks in fetal cardiac abnormalities reported in the epidemiology literature do not establish a causal association for lithium salts and Ebstein's anomaly.

Obesogenic polystyrene microplastic exposures disrupt the gut-liver-adipose axis.

Microplastics (MP) derived from the weathering of polymers, or synthesized in this size range, have become widespread environmental contaminants and have found their way into water supplies and the food chain. Despite this awareness, little is known about the health consequences of MP ingestion. We have previously shown that the consumption of polystyrene (PS) beads was associated with intestinal dysbiosis and diabetes and obesity in mice. To further evaluate the systemic metabolic effects of PS on the gut-liver-adipose tissue axis, we supplied C57BL/6J mice with normal water or that containing 2 sizes of PS beads (0.5 and 5 µm) at a concentration of 1 µg/ml. After 13 weeks, we evaluated indices of metabolism and liver function. As observed previously, mice drinking the PS-containing water had a potentiated weight gain and adipose expansion. Here we found that this was associated with an increased abundance of adipose F4/80+ macrophages. These exposures did not cause nonalcoholic fatty liver disease but were associated with decreased liver:body weight ratios and an enrichment in hepatic farnesoid X receptor and liver X receptor signaling. PS also increased hepatic cholesterol and altered both hepatic and cecal bile acids. Mice consuming PS beads and treated with the berry anthocyanin, delphinidin, demonstrated an attenuated weight gain compared with those mice receiving a control intervention and also exhibited a downregulation of cyclic adenosine monophosphate (cAMP) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. This study highlights the obesogenic role of PS in perturbing the gut-liver-adipose axis and altering nuclear receptor signaling and intermediary metabolism. Dietary interventions may limit the adverse metabolic effects of PS consumption.

Psychotropic Drug-Related Weight Gain and Its Treatment.

Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial.

AIM: To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals. METHODS: A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software. RESULTS: Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary. CONCLUSION: In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.

Association of hair polychlorinated biphenyls and multiclass pesticides with obesity, diabetes, hypertension and dyslipidemia in NESCAV study.

Obesity, diabetes, hypertension and dyslipidemia are well-established risk factors for cardiovascular diseases (CVDs), and have been associated with exposure to persistent organic pollutants. However, studies have been lacking as regards effects of non-persistent pesticides on CVD risk factors. Here, we investigated whether background chronic exposure to polychlorinated biphenyls (PCBs) and multiclass pesticides were associated with the prevalence of these CVD risk factors in 502 Belgian and 487 Luxembourgish adults aged 18-69 years from the Nutrition, environment and cardiovascular health (NESCAV) study 2007-2013. We used hair analysis to evaluate the chronic internal exposure to three PCBs, seven organochlorine pesticides (OCs) and 18 non-persistent pesticides. We found positive associations of obesity with hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and chlorpyrifos, diabetes with pentachlorophenol (PCP), fipronil and fipronil sulfone, hypertension with PCB180 and chlorpyrifos, and dyslipidemia with diflufenican and oxadiazon, among others. However, we also found some inverse associations, such as obesity with PCP, diabetes with γ-HCH, hypertension with diflufenican, and dyslipidemia with chlorpyrifos. These results add to the existing evidence that OC exposure may contribute to the development of CVDs. Additionally, the present study revealed associations between CVD risk factors and chronic environmental exposure to currently used pesticides such as organophosphorus and pyrethroid pesticides.

Safety and efficacy of remimazolam tosilate combined with low-dose fentanyl for procedural sedation in obese patients undergoing gastroscopy: study protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Obese patients are susceptible to hypoxaemia during procedural sedation. Propofol combined with low-dose opioids is commonly used as a sedation strategy, but it can exacerbate hypoxaemia by causing cardiopulmonary depression and airway obstruction, especially in obese patients. Remimazolam, a novel ultra-short-acting benzodiazepine, has minimal accumulative effects and less cardiorespiratory depression. This study aims to evaluate the safety and efficacy of combining remimazolam tosilate with low-dose fentanyl as an alternative option for procedural sedation in obese patients undergoing gastroscopy. METHODS AND ANALYSIS: This randomised controlled trial (RCT) will be conducted in the Endoscopy Centre of the First Affiliated Hospital of Xiamen University, recruiting 174 participants scheduled for painless gastroscopy with a body mass index of 30-39.9 kg×m-2. All patients will be randomly divided into two groups in a 1:1 ratio. The sedation strategy of the intervention group is remimazolam tosilate combined with fentanyl, while the control group is propofol combined with fentanyl. The primary outcome is the incidence of hypoxaemia and the secondary outcomes include the time to ambulation, need for airway manoeuvres and rescue sedation, sleep quality, the incidence of sedation failure, adverse events and the cost of sedatives. All statistical tests will be performed using IBM SPSS V.20.0 statistical software. A p value<0.05 is considered statistically significant. ETHICS AND DISSEMINATION: This RCT was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Xiamen University (Scientific Research Ethics Review 2022, No.093). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200067076.

Early-life exposure to residential black carbon and childhood cardiometabolic health.

BACKGROUND: Early life exposure to air pollution, such as particulate matter ≤2.5 µm (PM2.5), may be associated with obesity and adverse cardiometabolic health outcomes in childhood. However, the toxicity of PM2.5 varies according to its chemical composition. Black carbon (BC) is a constituent of PM2.5, but few studies have examined its impact on childhood cardiometabolic health. Therefore, we examined relationships between prenatal and early childhood exposure to BC and markers of adiposity and cardiometabolic health in early childhood. METHODS: This study included 578 mother-child pairs enrolled in the Healthy Start study (2009-2014) living in the Denver-metro area. Using a spatiotemporal prediction model, we assessed average residential black carbon levels during pregnancy and in the year prior to the early childhood follow-up visit at approximately 5 years old. We estimated associations between prenatal and early childhood BC and indicators of adiposity and cardiometabolic biomarkers in early childhood (mean 4.8 years; range, 4.0, 8.3), using linear regression. RESULTS: We found higher early childhood BC was associated with higher percent fat mass, fat mass index, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR), and lower leptin and waist circumference at approximately 5 years old, after adjusting for covariates. For example, per interquartile range (IQR) increase in early childhood BC (IQR, 0.49 µg/m3) there was 3.32% higher fat mass (95% CI; 2.05, 4.49). Generally, we did not find consistent evidence of associations between prenatal BC and cardiometabolic health outcomes in early childhood, except for an inverse association between prenatal BC and adiponectin, an adipocyte-secreted hormone typically inversely associated with adiposity. CONCLUSIONS: Higher early childhood, but not in utero, ambient concentrations of black carbon, a component of air pollution, were associated with greater adiposity and altered insulin homeostasis at approximately 5 years old. Future studies should examine whether these changes persist later in life.

The phenotypic heterogeneity of obese and nonobese patients with severe asthma and comparison of omalizumab-mepolizumab treatment efficiency in these patients.

In obese severe asthmatics, the degree of type 2 inflammation may vary according to their atopic status and past smoking history. In this study, we aimed to analyze the clinical and physiopathological features of obese and nonobese severe asthmatics treated with omalizumab or mepolizumab treatment. In addition we aimed to compare the clinical, spirometric outcomes and total peripheral eosinophilic count (TEC) changes after treatment with these 2 biologic agents in obese and nonobese groups. In this retrospective, cross sectional study, 121 severe asthmatic treated with biologic agents (omalizumab = 88 or mepolizumab = 33) for at least 16 weeks were included. Obese (n: 44) and nonobese severe asthmatics (n: 77) were analyzed according to whether they provided a ≥ 10 pack/years (p/y) or <10 p/y smoking history and were found to be atopic. Obese and nonobese groups were compared in terms of the change in the asthma control test, asthma attacks, TEC, and forced expiratory volume in the first second (FEV1) after treatment. In patients with ≥10 p/y smoking history, nonobese group had a significantly higher TEC compared to obese group [median (min-max) 660 cells/µL (200-1500) vs 300 cells/µL (110-770); p: 0.013]. Within the nonobese group, nonatopic patients had a significantly higher TEC compared to atopic patients [median (min-max) 1200 cells/µL (100-2100) vs 310 cells/µL (0-2730); p: 0.021]. Both biologic agents had similar effects on improving asthma control test and in reducing asthma attacks; however, mepolizumab was more effective in suppressing TEC. The improvement in FEV1 in obese group following biologic 2 agents was very similar but in nonobese group, mepolizumab was found to be superior (510 mL vs. 295 mL; p: 0.034). In our real-life study, nonobese severe asthmatics with ≥10 p/y smoking history and those that were nonatopic had higher TEC. Compared to omalizumab, mepolizumab was superior at reducing TEC in all asthmatics and in improving FEV1 in nonobese group.

2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2.

Obesity is a popular public health problem worldwide and is mainly caused by overeating, but little is known about the impacts of synthetic chemicals on obesity. Herein, we evaluated the obesogenic effect caused by 2-ethylhexyl diphenyl phosphate (EHDPHP) on zebrafish. Adult zebrafish were exposed to 5, 35, and 245 µg/L of EHDPHP for 21 days. Results showed that EHDPHP exposure significantly promoted the feeding behavior of zebrafish, as evidenced by shorter reaction time, increased average food intake, feeding rate, and intake frequency (p < 0.05). Transcriptomic, real-time quantitative PCR, and neurotransmitter analyses revealed that the dopamine (DA) receptor D2 (DRD2) was inhibited, which interfered with the DA neural reward regulation system, thus stimulating food addiction to zebrafish. This was further verified by the restored DRD2 after 7 days of Halo (a DRD2 agonist) treatment. A strong interaction between EHDPHP and DRD2 was identified via molecular docking. As a consequence of the abnormal feeding behavior, the exposed fish exhibited significant obesity evidenced by increased body weight, body mass index, plasma total cholesterol, triglyceride, and body fat content. Additionally, the pathways linked to Parkinson's disease, alcoholism, and cocaine addiction were also disrupted, implying that EHDPHP might cause other neurological disorders via the disrupted DA system.

Associations of multiple air pollutants with kidney function in normal-weight and obese adults and effect modification by free fatty acids.

Increasing studies have linked air pollution to kidney dysfunction, however, the associations between the mixture of air pollutants and kidney function and potential effect modifiers remain unclear. We aimed to investigate whether obese adults were more susceptible than normal-weight ones to the joint effects of multiple air pollutants on kidney function and further to explore effect modification by free fatty acids (FFAs). Forty obese and 49 normal-weight adults were recruited from a panel study (252 follow-up visits). Individual exposure levels of air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO) were estimated. Glomerular function (cystatin C (CysC) and estimated glomerular filtration rate (eGFR)) and tubular function (neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1) were evaluated. Plasma levels of FFAs including trans fatty acids (TFAs) and essential fatty acids (EFAs) were quantified using targeted metabolomics. Bayesian kernel machine regression model was applied to estimate the associations between the mixture of air pollutants and kidney function. The results showed significant joint effects of air pollutants on kidney function indicators. In the normal-weight group, the mixture of air pollutants was significantly associated with CysC and eGFRcr-cys when the mixture was at or above its 70 percentile compared with the median, where O3 was identified as the key pollutant. In the obese group, a significantly positive association between the pollutant mixture and NGAL was observed in addition to trends in CysC and eGFRcr-cys, mainly driven by SO2. Interaction analysis suggested that the associations of air pollutants with kidney function were augmented by TFAs in both groups and weakened by EFAs in the normal-weight group. This study highlighted the renal adverse effects of air pollutants and modification of FFAs, which has implications for target prevention for kidney dysfunction associated with air pollution, especially among vulnerable populations.

Metagenomics study on taxonomic and functional change of gut microbiota in patients with obesity with PCOS treated with exenatide combination with metformin or metformin alone.

OBJECTIVE: To investigate the effect of exenatide treatment on the composition of intestinal flora and metabolic pathways in patients with obesity with polycystic ovary syndrome. METHODS: Patients with obesity with polycystic ovary syndrome (PCOS) were distributed to two groups: one received exenatide combined with metformin (COM group, n = 14) and the other used metformin alone (MF group, n = 15). Fresh fecal specimens from the participants, including 29 patients with obesity with PCOS and 6 healthy controls, were collected for metagenomic sequencing. The effect of exenatide combination with metformin or metformin alone on the composition and function of intestinal flora in patients with obesity with PCOS were compared by bioinformatics analysis. RESULTS: The level of BMI, TT, HbA1c, and HDL-c was significantly improved in both groups. The MF and COM groups were abundant in Firmicutes, Bacteroidetes, Uroviricota, Actinobacteria, and Proteobacteria. Abundance of Bacteroidetes, Proteobacteria, Hungatella, and certain probiotics like Phocaeicola and Anaerobutyricum significantly increased in both groups after treatment. Enriched microbial species in the MF and COM group were different. Clostridium, Fusobacterium, and Oxalobacter were the main bacteria in the post-MF group, while Lactococcus_garvieae, Clostridium_perfringens, and Coprococcus_sp_AF16_5 were the main bacteria in the post-COM group. The post-COM group had more probiotic species including Bifidobacterium, Prevotella, and Anaerobutyricum after treatment. CONCLUSION: Both exenatide combined with metformin and metformin monotherapy can improve metabolic and endocrine markers, and the diversity and abundance of gut microbiota in patients with obesity with PCOS. The effects of the combination and monotherapy agents on intestinal flora were consistent to some extent but also unique respectively.

Short-term effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome: a pilot randomized trial.

Objective: To observe the effect of beinaglutide combined with metformin versus metformin alone on weight loss and metabolic profiles in obese patients with polycystic ovary syndrome(PCOS). Methods: A total of 64 overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomly assigned to metformin(MET) 850 mg twice a day(BID) or combined MET 850 mg BID with beinaglutide (COMB) starting at 0.1mg three times a day(TID)and increasing to 0.2mg TID two weeks later. The main endpoints were changes in anthropometric measurements of obesity. Glucose and lipid metabolic, gonadal profiles, and antral follicle count changes as secondary outcomes were also observed. Results: 60(93.75%) patients completed the study. In terms of lowering weight, body mass index (BMI),waist circumference(WC) and waist to height ratio(WHtR), COMB treatment outperformed MET monotherapy. Subjects in the COMB arm lost weight 4.54±3.16kg compared with a 2.47±3.59kg loss in the MET arm. In the COMB group, BMI,WC and WHtR were reduced significantly compared with that in the MET group, respectively. COMB therapy is also more favorable in the reduction of fasting insulin(FINS), total testosterone(TT), and homeostasis model assessment-insulin resistance(HOMA-IR) when compared to MET therapy. Antral follicle count and ovarian volume were non-significantly changed in both groups.The most frequent side effects in both groups were mild and moderate digestive symptoms. Itching and induration at the injection site were reported with COMB treatment. Conclusion: Short-term combined treatment with beinaglutide and metformin appears superior to metformin monotherapy in lowering body weight, BMI, WC,WHtR and improving insulin sensitivity and androgen excess in women with PCOS and obesity, with tolerable adverse events. Clinical trial registration: https://www.chictr.org.cn/listbycreater.aspx, identifier ChiCTR2000033741.

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.

BACKGROUND: Obesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity. METHODS: In this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point). RESULTS: A total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% in the placebo group. At week 36, the mean change ranged from -9.4% to -14.7% with orforglipron and was -2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class. CONCLUSIONS: Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.).

Efficacy and Safety of a Subanesthetic Dose of Esketamine Combined with Propofol in Patients with Obesity Undergoing Painless Gastroscopy: A Prospective, Double-Blind, Randomized Controlled Trial.

Purpose: Patients with obesity are more susceptible to hypoxemia. Anesthetic management for patients with obesity undergoing painless gastroscopy presents a severe challenge for anesthesiologists. Esketamine is a NMDA antagonist that has been proven to be beneficial for ameliorating respiratory depression owing to its sympathomimetic effect; however, there are no relevant reports on its use in patients with obesity. We designed a randomized controlled trial to evaluate whether esketamine can be the ideal adjuvant to propofol sedation in patients with obesity undergoing painless gastroscopy. Patients and Methods: A total of 104 patients with obesity undergoing painless gastroscopy were randomly divided into group C (propofol+saline) and group S (propofol+esketamine 0.25 mg/kg). Anesthesia was induced by 2 mg/kg propofol with saline or esketamine. The consumption of propofol, hemodynamic parameters, duration of procedure, induction time, postoperative awakening time, and orientation recovery time were recorded. Adverse events and satisfaction scores were also recorded. Results: Propofol consumption was 274.4±22.6 mg and 201.3±16.6 mg in groups C and S, respectively. The induction time of groups C and S were 25.4±2.3 s and 17.8±1.9 s, respectively. The postoperative awakening times of groups C and S were 6.2±1.1 min and 4.8±1.3 min, respectively. Hemodynamic parameters were more stable in group S than in group C. The incidence of adverse events such as injection pain, hypoxemia, hypotension, bradycardia, choking, and body movement were significantly lower in group S. The satisfaction scores of the endoscopist and anesthesiologist were (4.58±0.49 vs 3.71±0.83) and (4.75±0.44 vs 3.33±0.92), respectively. Conclusion: The combination of propofol and esketamine (0.25 mg/kg) improves the safety and reduces the incidence of adverse events in patients with obesity during painless gastroscopy. Thus, this method is worthy of clinical application. Clinical Trials Registration: ChiCTR 2200062547.

Pharmacotherapy for obesity: recent evolution and implications for cardiovascular risk reduction.

INTRODUCTION: Obesity is highly prevalent in the U.S. and is associated with an increased risk of major adverse cardiovascular events (MACE). Modalities for the management of obesity include lifestyle intervention, pharmacotherapy, and bariatric surgery. AREAS COVERED: This review describes the evidence on the effects of weight loss therapies on MACE risk. Lifestyle interventions and older antiobesity pharmacotherapies have been associated with <12% body weight reduction and no clear benefit to reduce MACE risk. Bariatric surgery is associated with substantial weight reduction (20-30%) and markedly lower subsequent risk for MACE. Newer antiobesity pharmacotherapies, particularly semaglutide and tirzepatide, have shown greater efficacy for weight reduction compared with older medications and are being evaluated in cardiovascular outcomes trials. EXPERT OPINION: Current practice for cardiovascular risk reduction in patients with obesity is lifestyle intervention for weight loss, combined with the treatment of obesity-related cardiometabolic risk factors individually. The use of medications to treat obesity is relatively rare. In part, this reflects concerns about long-term safety and weight loss effectiveness, possible provider bias, as well as lack of clear evidence of MACE risk reduction. If ongoing outcomes trials demonstrate the efficacy of newer agents in reducing MACE risk, this will likely lead to expanded use in obesity management.

Assessing farmer's exposure to pesticides and the risk for non-communicable diseases: A biomonitoring study.

This cross-sectional study aimed to assess the adverse effects of pesticide use in humans, such as non-communicable diseases, using acetylcholinesterase (AChE) and pesticide concentrations in blood samples. A total of 353 samples (290 case and 63 control) were collected from participants with >20 years of experience in agricultural pesticide use. The pesticide and AChE concentrations were determined using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) and Reverse Phase High Performance Liquid Chromatography (RP-HPLC). Various health risks from pesticide exposure were assessed, including dizziness or headache, tension, anxiety, confusion, loss of appetite, loss of balance, concentration difficulties, irritability, anger, and depression. These risks may be influenced by the duration and intensity of exposure, the type of pesticide, and environmental factors in the affected areas. A total of 26 pesticides were detected in the blood samples from the exposed population, including 16 insecticides, three fungicides, and seven herbicides. Pesticide concentrations ranged from 0.20 to 12.12 ng/mL, and were statistically significant between the case and control groups (p < 0.05, p < 0.01, and p < 0.001). A correlation analysis was performed to determine statistically significance between pesticide concentration and symptoms of non-communicable diseases, such as Alzheimer's, Parkinson's, obesity, and diabetes. The estimated AChE levels in case and control blood samples were 21.58 ± 2.31 and 24.13 ± 1.08 U/mL, respectively (mean ± SD). The AChE levels were significantly lower in case samples than in controls (p < 0.001), which is considered to be an effect of long-term pesticide exposure, and is the cause of Alzheimer's disease (p < 0.001), Parkinson's disease (p < 0.001), and obesity (p < 0.01). Chronic exposure to pesticides and low levels of AChE are somewhat related to non-communicable diseases.

Weight loss efficiency and safety of tirzepatide: A Systematic review.

OBJECTIVE: Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study. METHODS: Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software. RESULTS: In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs. CONCLUSION: In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.

Outdoor air pollution and histologic composition of normal breast tissue.

BACKGROUND: Biologic pathways underlying the association between outdoor air pollution and breast cancer risk are poorly understood. Breast tissue composition may reflect cumulative exposure to breast cancer risk factors and has been associated with breast cancer risk among patients with benign breast disease. Herein, we evaluated whether fine particulate matter (PM2.5) was associated with the histologic composition of normal breast tissue. METHODS: Machine-learning algorithms were applied to digitized hematoxylin and eosin-stained biopsies of normal breast tissue to quantify the epithelium, stroma, adipose and total tissue area from 3,977 individuals aged 18-75 years from a primarily Midwestern United States population who donated breast tissue samples to the Susan G. Komen Tissue Bank (2009-2019). Annual levels of PM2.5 were assigned to each woman's residential address based on year of tissue donation. We applied predictive k-means to assign participants to clusters with similar PM2.5 chemical composition and used linear regression to examine the cross-sectional associations between a 5-µg/m3 increase in PM2.5 and square root-transformed proportions of epithelium, stroma, adipose, and epithelium-to-stroma proportion [ESP], overall and by PM2.5 cluster. RESULTS: Higher residential PM2.5 was associated with lower proportion of breast stromal tissue [ß = -0.93, 95% confidence interval: (-1.52, -0.33)], but was not related to the proportion of epithelium [ß = -0.11 (-0.34, 0.11)]. Although PM2.5 was not associated with ESP overall [ß = 0.24 (-0.16, 0.64)], the association significantly differed by PM2.5 chemical composition (p-interaction = 0.04), with a positive association evident only among an urban, Midwestern cluster with higher concentrations of nitrate (NO3-) and ammonium (NH4+) [ß = 0.49 (0.03, 0.95)]. CONCLUSIONS: Our findings are consistent with a possible role of PM2.5 in breast cancer etiology and suggest that changes in breast tissue composition may be a potential pathway by which outdoor air pollution impacts breast cancer risk. This study further underscores the importance of considering heterogeneity in PM2.5 composition and its impact on breast carcinogenesis.

Type 1 diabetes and diet-induced obesity predispose C57BL/6J mice to PM2.5-induced lung injury: a comparative study.

BACKGROUND: Pre-existing metabolic diseases may predispose individuals to particulate matter (PM)-induced adverse health effects. However, the differences in susceptibility of various metabolic diseases to PM-induced lung injury and their underlying mechanisms have yet to be fully elucidated. RESULTS: Type 1 diabetes (T1D) murine models were constructed by streptozotocin injection, while diet-induced obesity (DIO) models were generated by feeding 45% high-fat diet 6 weeks prior to and throughout the experiment. Mice were subjected to real-ambient PM exposure in Shijiazhuang City, China for 4 weeks at a mean PM2.5 concentration of 95.77 µg/m3. Lung and systemic injury were assessed, and the underlying mechanisms were explored through transcriptomics analysis. Compared with normal diet (ND)-fed mice, T1D mice exhibited severe hyperglycemia with a blood glucose of 350 mg/dL, while DIO mice displayed moderate obesity and marked dyslipidemia with a slightly elevated blood glucose of 180 mg/dL. T1D and DIO mice were susceptible to PM-induced lung injury, manifested by inflammatory changes such as interstitial neutrophil infiltration and alveolar septal thickening. Notably, the acute lung injury scores of T1D and DIO mice were higher by 79.57% and 48.47%, respectively, than that of ND-fed mice. Lung transcriptome analysis revealed that increased susceptibility to PM exposure was associated with perturbations in multiple pathways including glucose and lipid metabolism, inflammatory responses, oxidative stress, cellular senescence, and tissue remodeling. Functional experiments confirmed that changes in biomarkers of macrophage (F4/80), lipid peroxidation (4-HNE), cellular senescence (SA-ß-gal), and airway repair (CCSP) were most pronounced in the lungs of PM-exposed T1D mice. Furthermore, pathways associated with xenobiotic metabolism showed metabolic state- and tissue-specific perturbation patterns. Upon PM exposure, activation of nuclear receptor (NR) pathways and inhibition of the glutathione (GSH)-mediated detoxification pathway were evident in the lungs of T1D mice, and a significant upregulation of NR pathways was present in the livers of T1D mice. CONCLUSIONS: These differences might contribute to differential susceptibility to PM exposure between T1D and DIO mice. These findings provide new insights into the health risk assessment of PM exposure in populations with metabolic diseases.