Life's essential 8 metrics and mortality outcomes in insulin resistance: The role of inflammation, vascular aging, and gender.

BACKGROUND: Insulin resistance (IR) elevates cardiovascular disease (CVD) and mortality risks. Insulin resistance (IR) increases the risk of CVDs and mortality. Recently, the American Heart Association introduced the Life's Essential 8 (LE8) framework to assess cardiovascular health (CVH). However, its impact on mortality in IR populations is unknown. METHODS: Analyzing 2005-2018 National Health and Nutrition Examination Survey data, we studied 5301 IR adults (≥20 years). LE8 scores were calculated and participants were categorized into low, moderate, and high CVH groups. Systemic immune-inflammation index (SII) and heart age/vascular age (HVA) were measured as potential mediators. Cox models estimated all-cause and CVD mortality hazard ratios (HRs), stratified by LE8 score and sex, and adjusted for covariates. Mediation analyses assessed SII and HVA's indirect effects. This study is an observational cohort study. RESULTS: Over a 7.5-year median follow-up, 625 deaths occurred, including 159 CVD-related. Compared to low CVH, moderate and high CVH groups showed reduced all-cause (HR = 0.72, 95% CI 0.58-0.89; HR = 0.38, 95% CI 0.22-0.67) and CVD mortality (HR = 0.42, 95% CI 0.26-0.69; HR = 0.15, 95% CI 0.04-0.57). A 10-point LE8 increase correlated with 15% and 31% reductions in all-cause and CVD mortality, respectively. SII and HVA mediated up to 38% and 12% of these effects. The LE8's protective effect was more pronounced in men. CONCLUSION: LE8 effectively evaluates CVH and lowers mortality risk in IR adults, partially mediated by SII and HVA. The findings inform clinical practice and public health strategies for CVD prevention in IR populations.

Heterogeneity of aging and mortality risk among individuals with hypertension: Insights from phenotypic age and phenotypic age acceleration.

OBJECTIVES: Hypertension, a key contributor to mortality, is impacted by biological aging. We investigated the relationship between novel biological aging metrics - Phenotypic Age (PA) and Phenotypic Age Acceleration (PAA) - and mortality in individuals with hypertension, exploring the mediating effects of arterial stiffness (estimated Pulse Wave Velocity, ePWV), and Heart/Vascular Age (HVA). METHODS: Using data from 62,160 National Health and Nutrition Examination Survey (NHANES) participants (1999-2010), we selected 4,228 individuals with hypertension and computed PA, PAA, HVA, and ePWV. Weighted, multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating PA, PAA to mortality, and mediation roles of ePWV, PAA, HVA were evaluated. Mendelian randomization (MR) analysis was employed to investigate causality between genetically inferred PAA and hypertension. RESULTS: Over a 12-year median follow-up, PA and PAA were tied to increased mortality risks in individuals with hypertension. All-cause mortality hazard ratios per 10-year PA and PAA increments were 1.96 (95% CI, 1.81-2.11) and 1.67 (95% CI, 1.52-1.85), respectively. Cardiovascular mortality HRs were 2.32 (95% CI, 1.97-2.73) and 1.93 (95% CI, 1.65-2.26) for PA and PAA, respectively. ePWV, PAA, and HVA mediated 42%, 30.3%, and 6.9% of PA's impact on mortality, respectively. Mendelian randomization highlighted a causal link between PAA genetics and hypertension (OR = 1.002; 95% CI, 1.000-1.003). CONCLUSION: PA and PAA, enhancing cardiovascular risk scores by integrating diverse biomarkers, offer vital insights for aging and mortality evaluation in individuals with hypertension, suggesting avenues for intensified aging mitigation and cardiovascular issue prevention. Validations in varied populations and explorations of underlying mechanisms are warranted.

Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study.

Background: Atrial fibrillation (AF) is the most common and persistent form of arrhythmia. Recently, increasing evidence has shown a link between immune responses and atrial fibrillation. However, whether the immune response is a cause or consequence of AF remains unknown. We aimed to determine whether genetically predicted peripheral immunity might have a causal effect on AF. Methods: First, we performed Mendelian randomization (MR) analyses using genetic variants strongly associated with neutrophil, eosinophil, basophil, lymphocyte, and monocyte cell counts as instrumental variables (IVs). Lymphocyte counts were then subjected to further subgroup analysis. The effect of immune cell counts on AF risk was measured using summary statistics from genome-wide association studies (GWAS). Results: Two-sample MR analysis revealed that a higher neutrophil count, basophil count and lymphocyte count had a causal effect on AF [Odds ratio (OR), 1.06, 95% confidence interval (CI), 1.01-1.10, P = 0.0070; OR, 1.10; 95% CI, 1.04-1.17; P = 0.0015; OR, 0.96; 95% CI, 0.93-0.99; P = 0.0359]. In addition, in our further analysis, genetically predicted increases in CD4 + T-cell counts were also associated with an increased risk of AF (OR, 1.04; 95% CI, 1.0-.09; P = 0.0493). Conclusion: Our MR analysis provided evidence of a genetically predicted causal relationship between higher peripheral immune cell counts and AF. Subgroup analysis revealed the key role of peripheral lymphocytes in AF, especially the causal relationship between CD4 + T cell count and AF. These findings are beneficial for future exploration of the mechanism of AF.

Arbutin Ameliorates Murine Colitis by Inhibiting JAK2 Signaling Pathway.

Background and objective: Abnormal activation of Janus kinase 2 (JAK2) promotes the pathogenesis and progress of inflammatory bowel disease (IBD) by stimulating the cytokine traffic. Based on docking studies, arbutin, a natural product extracted from a traditional medicinal plant bearberry, was found to bind to JAK2. The study aimed to investigate the effects and mechanisms of regulating JAK2 by arbutin on colitis in mice. Methods: A mice colitis model was established to mimic human IBD. The mice freely drank water containing dextran sulfate sodium. Inflammation in epithelial (IEC6) and immune (RAW264.7) cells was analyzed following treatment with lipopolysaccharides (LPS). Results: Colitis symptoms, including body weight loss, increased disease activity index, and increased colon weight/length ratio, were significantly alleviated by arbutin. Mediators of colonic pro-inflammatory cytokines as well as apoptosis markers in colitis were suppressed by the glycoside. High expression of phosphorylated JAK2 in colitis was significantly reversed by arbutin. The effects of arbutin treatment on colitis were considerably inhibited by the JAK2 inhibitor AG490. LPS-induced inflammatory responses were also suppressed by arbutin, which was notably inhibited by the JAK2 inhibitor AG490. Conclusion: The findings obtained herein suggest the protective role of arbutin and provide novel insights into alternative colitis treatments, which involve inhibition of the JAK2 signaling pathway.

Sudden cardiac death in patients with myocardial infarction: 1.5 primary prevention.

Sudden cardiac death (SCD) is one of the most common causes of death in the world. Coronary heart disease (CHD) is the root cause of most patients with SCD, and myocardial infarction (MI) is the main cause of SCD among all types of CHD. Early identification of high-risk patients after an MI, and the application of related prevention strategies and disease-specific treatments will be the key to reduce SCD. The mechanism of SCD after MI varies over time, and the relevant risk prediction indicators are also dynamic and different. In the existing guidelines for MI patients, the static and slightly single stratification of primary (PP) and secondary (SP) prevention has significant room for improvement. The 1.5 primary prevention (1.5PP) is defined as patients with PP who also had the following risk factors: non-sustained ventricular tachycardia (NSVT), frequent premature ventricular contractions (PVCs), severe heart failure (left ventricular ejection fraction, LVEF <25%), and syncope or pre-syncope. The emergence of 1.5PP has provided a new method for the stratification and management of SCD after an MI.

Evolution of brachytherapy treatment planning to deterministic radiation transport for calculation of cardiac dose.

Brachytherapy was among the first methods of radiotherapy and has steadily continued to evolve. Here we present a brief review of the progression of dose calculation methods in brachytherapy to the current state-of-the art computerized methods for heterogeneity correction. We further review the origin and development of the BrachyVision (Varian Medical Systems, Inc., Palo Alto, CA) treatment planning system and evaluate dosimetric results from 12 patients implanted with the strut-assisted volumetric implant (SAVI) applicator (Cianna Medical, Aliso Viejo, CA) for accelerated partial breast irradiation (APBI). Dosimetric results from plans calculated using homogenous and heterogeneous algorithms have been compared to investigate the impact of heterogeneity corrections. Our study showed large percent difference between mean cardiac doses 11.8 ± 6.2% (p = 0.0007) calculated with and without heterogeneity corrections. Our findings are consistent with those of others, indicating an overestimation of the distal dose to organs-at-risk by traditional methods, especially at interfaces between air and tissue.

Gene expression profiling in the thiamethoxam resistant and susceptible B-biotype sweetpotato whitefly, Bemisia tabaci.

Thiamethoxam has been used as a major insecticide to control the B-biotype sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Due to its excessive use, a high level of resistance to thiamethoxam has developed worldwide over the past several years. To better understand the molecular mechanisms underlying this resistance in B. tabaci, gene profiles between the thiamethoxam-resistant and thiamethoxam-susceptible strains were investigated using the suppression subtractive hybridization (SSH) library approach. A total of 72 and 52 upand down-regulated genes were obtained from the forward and reverse SSH libraries, respectively. These expressed sequence tags (ESTs) belong to several functional categories based on their gene ontology annotation. Some categories such as cell communication, response to abiotic stimulus, lipid particle, and nuclear envelope were identified only in the forward library of thiamethoxam-resistant strains. In contrast, categories such as behavior, cell proliferation, nutrient reservoir activity, sequence-specific DNA binding transcription factor activity, and signal transducer activity were identified solely in the reverse library. To study the validity of the SSH method, 16 differentially expressed genes from both forward and reverse SSH libraries were selected randomly for further analyses using quantitative realtime PCR (qRT-PCR). The qRT-PCR results were fairly consistent with the SSH results; however, only 50% of the genes showed significantly different expression profiles between the thiamethoxam-resistant and thiamethoxam-susceptible whiteflies. Among these genes, a putative NAD-dependent methanol dehydrogenase was substantially over-expressed in the thiamethoxamresistant adults compared to their susceptible counterparts. The distributed profiles show that it was highly expressed during the egg stage, and was most abundant in the abdomen of adult females.

Induction effects of host plants on insecticide susceptibility and detoxification enzymes of Bemisia tabaci (Hemiptera: Aleyrodidae).

BACKGROUND: The polyphagous B-biotype Bemisia tabaci (Gennadius) has developed a high resistance to commonly used insecticides in China. To illustrate the induced changes by host plant, bioassay and biochemical research on five different host populations were investigated. RESULTS: Except for bifenthrin, all tested insecticides showed lower toxicity to the B. tabaci poinsettia population compared with other host populations. Moreover, four insecticides, the exceptions being abamectin and fipronil, showed highest toxicity towards the tomato population. The LC(50) values of the poinsettia population, particularly towards acetamiprid, were 14.8-, 10.3- and 7.29-fold higher than those of tomato, cucumber and cabbage respectively. The CarE activities of B. tabaci cabbage and cucumber populations were all significantly higher than those of poinsettia, cotton and tomato populations. The ratio of the cabbage population was 1.97-, 1.79- and 1.30-fold higher than that of poinsettia, cotton and tomato respectively. The frequency profiles for this activity also have obvious differences. The GST and P450 activities of the cucumber population were the lowest in the five host populations. CONCLUSION: Long-term induction of host plants for B-biotype B. tabaci could influence their susceptibilities to several insecticides. Rational selection and usage of insecticides for particular hosts will be helpful for resistance management and control of this species.

Cross-resistance study and biochemical mechanisms of thiamethoxam resistance in B-biotype Bemisia tabaci (Hemiptera: Aleyrodidae).

BACKGROUND: B-biotype Bemisia tabaci (Gennadius) has invaded China over the past two decades. To understand the risks and to determine possible mechanisms of resistance to thiamethoxam in B. tabaci, a resistant strain was selected in the laboratory. Cross-resistance and the biochemical mechanisms of thiamethoxam resistance were investigated in the present study. RESULTS: A 66.3-fold thiamethoxam-resistant B. tabaci strain (TH-R) was established after selection for 36 generations. Compared with the susceptible strain (TH-S), the selected TH-R strain showed obvious cross-resistance to imidacloprid (47.3-fold), acetamiprid (35.8-fold), nitenpyram (9.99-fold), abamectin (5.33-fold) and carbosulfan (4.43-fold). No cross-resistance to fipronil, chlorpyrifos or deltamethrin was seen. Piperonyl butoxide (PBO) and triphenyl phosphate (TPP) exhibited significant synergism on thiamethoxam effects in the TH-R strain (3.14- and 2.37-fold respectively). However, diethyl maleate (DEM) did not act synergistically with thiamethoxam. Biochemical assays showed that cytochrome P450 monooxygenase activities increased 1.21- and 1.68-fold respectively, and carboxylesterase activity increased 2.96-fold in the TH-R strain. However, no difference was observed for glutathione S-transferase between the two strains. CONCLUSION: B-biotype B. tabaci develops resistance to thiamethoxam. Cytochrome P450 monooxygenase and carboxylesterase appear to be responsible for the resistance. Reasonable resistance management that avoids the use of cross-resistance insecticides may delay the development of resistance to thiamethoxam in this species.