Visceral adiposity associated with incidence and development trajectory of cardiometabolic diseases: A prospective cohort study.

BACKGROUND AND AIMS: There is a lack of literature concerning the effects of visceral adipose on the development of first cardiometabolic disease (FCMD) and its subsequent progression to cardiometabolic multimorbidity (CMM) and mortality. METHODS AND RESULTS: 423,934 participants from the UK Biobank with different baseline disease conditions were included in the analysis. CMM was defined as the simultaneous presence of coronary heart disease, T2D, and stroke. Visceral adiposity was estimated by calculating the visceral adiposity index (VAI). Multistate models were used to assess the effect of visceral adiposity on the development of CMM. During a median follow-up of 13.5 years, 50,589 patients had at least one CMD, 6131 were diagnosed with CMM, whereas 24,634 patients died. We observed distinct roles of VAI with respect to different disease transitions of CMM. HRs (95 % CIs) of high VAI were 2.35 (2.29-2.42) and 1.64 (1.50-1.79) for transitions from healthy to FCMD and from FCMD to CMM, and 0.97 (0.93-1.02) for all-cause mortality risk from healthy, FCMD and CMM, respectively. CONCLUSIONS: Our study provides the first evidence that visceral adipose may contribute to the development of FCMD and CMM in healthy participants. However, visceral adipose may confer resistance to all-cause mortality in participants with existing CMD or CMM. A better understanding of the relationship between visceral adipose and CMM can focalize further investigations on patients with CMD with high levels of visceral fat and help take targeted preventive measures to reduce the medical burden on individual patients and society.

Trajectories of quality of life and cognition in different multimorbidity patterns: Evidence from SHARE.

OBJECTIVES: The study aimed to observe the trajectory of quality of life (QoL) and cognition, and to a analyze the bidirectional association between cognition and QoL for diverse multimorbidity patterns. METHODS: In total, 16,153 older participants age ≥50 years were included from the Survey of Health, Ageing and Retirement in Europe (SHARE). We used latent class analysis (LCA) to identify multimorbidity patterns in the baseline population. We used linear mixed models (LMM) to examine the trajectory of cognition and QoL in different multimorbidity patterns. A cross-lagged model was employed to analyze the bidirectional association between cognition and QoL in diverse multimorbidity patterns. RESULTS: Latent class analysis identified four multimorbidity patterns: high and low comorbidity burden (HC and LC), cardiometabolic (CA), and osteoarthrosis (OS). The HC group had the poorest cognitive function and QoL (p for trend < 0.001). Delayed and immediate episodic memory in the OS group declined at a highest rate (p for trend < 0.001). Additionally, a bidirectional association between cognition and QoL was observed. The effect of cognitive function on QoL was relatively stronger than the reverse in the CA and LC groups. CONCLUSIONS: The rate of decline in cognition and QoL over the time differs in diverse multimorbidity patterns, and patients with four or more chronic diseases should be specially considered. Notably, early monitoring of cognitive function and can help break the vicious cycle between cognitive deterioration and poor QoL in patients with OS or CA diseases.

Ultra-processed food consumption, mediating biomarkers, and risk of chronic obstructive pulmonary disease: a prospective cohort study in the UK Biobank.

Background: Ultra-processed food (UPF) is a popular supplement in the UK and other developed countries. However, whether and how UPF intake is associated with chronic obstructive pulmonary disease (COPD) remains unclear. Objective: We aimed to examine the association between UPF consumption and COPD incidence and explore the potential mediating effects of COPD-related biomarkers. Methods: This prospective cohort study included 207 002 participants without COPD at recruitment and completed 24-hour dietary recalls. UPF was defined according to the NOVA classification system. Incident COPD was ascertained using electronic hospital and mortality records. Cox regression models were used to estimate UPF consumption and the subsequent risk of COPD. Substitution analysis was performed to assess the risk of COPD by substituting UPF with an equivalent proportion of unprocessed or minimally processed food (UNPF). Mediation analyses were performed to evaluate the contribution of biomarkers related to the lipid profile, glucose metabolism, and systemic inflammation to the observed associations. Results: During a median follow-up of 13.1 (interquartile range: 12.5-13.9) years, 4670 COPD events were recorded. The adjusted hazard ratio (HR) of COPD in the highest quintile versus the lowest quintile of the UPF consumption proportion (weight percentage of the UPF) was 1.22 (95% confidence interval [CI]: 1.11-1.34). There was a 10% elevated risk of COPD incidence per SD increase in UPF intake (HR: 1.10; 95% CI: 1.08-1.13). Replacing 20% of the UNPF weight with the UPF was associated with a 13% decrease in COPD risk (95% CI: 0.84-0.91). In mediation analyses, biomarkers explained 1.0-10.1% of the association between UPF intake and COPD. Results from stratified and sensitivity analyses further support the robustness of these findings. Conclusions: Elevated UPF consumption was associated with a higher risk of COPD, and this association was primarily mediated by glucose, inflammation, and lipids, whereas substituting UNPF for UPF was associated with a decreased risk of COPD.

Association between coffee and incident heart failure: A prospective cohort study from the UK Biobank.

BACKGROUND AND AIMS: The relationship between coffee consumption and heart failure (HF) incidence is inconclusive. This study aimed to explore the association between time-varying coffee consumption and incident HF using a longitudinal study design. METHODS AND RESULTS: Data were obtained from the UK Biobank, comprising 497,503 adults (age, 56.5 ± 8.1 years; 54.6% women) who were free from HF at baseline in 2006-2010. The median follow-up time for the HF incidence was 11.9 years. Marginal structural models (MSM) were employed to adjust for potential time-varying confounders and account for bias caused by loss of follow-up. Furthermore, we used a restricted cubic spline to test and describe the nonlinear relationship between coffee consumption and HF risk. At baseline, 70.5% of participants reported drinking ≥1 cups/d coffee and 2.7% participants developed HF. After adjusting for potential confounders, we identified a nonlinear J-shaped association between coffee consumption and HF risk (P < 0.001). Compared with drinking coffee <1 cups/d, 1-2 cups/d (HR = 0.878; 95% CI: 0.838-0.920), 3-4 cups/d (HR = 0.920; 95% CI: 0.869-0.974) may be associated with a reduced risk of HF, while >6 cups/d (HR = 1.209; 95% CI: 1.056-1.385) may be associated with a higher risk of HF. However, sensitive analyses stratified by gender and smoking status indicated that >6 cups/d does not significantly increase the risk of HF. Additionally, the type of coffee was found to significant impact on the incidence of HF (P < 0.05). CONCLUSION: In this large cohort of UK adults, moderate coffee consumption may reduce risk of HF incidence.

Association of ultra-processed food consumption with incident depression and anxiety: a population-based cohort study.

Background: Global ultra-processed food (UPF) consumption has risen rapidly. The development and prognosis of depression and anxiety remain unclarified. Herein, we aimed to examine the association between UPF consumption and the incidence and progression trajectory of depression and anxiety. Methods: In our study, participants were recruited between 2006 and 2010. UPF consumption was expressed as UPF servings, energy ratio, and weight ratio. The relationships between UPF consumption and depression or anxiety were assessed using the Cox proportional hazards model. Multi-state models were used to explore the association between UPF consumption and the risks of all transitions from a healthy state to depression or anxiety and then to all-cause mortality. Results: Among the 183 474 participants, 5453 were diagnosed with depression and 6763 with anxiety during the follow-up of 13.1 years. The participants in the highest quartile (Q4) of UPF servings, energy ratio, and weight ratio had an increased risk of depression compared to those in the lowest quartile (Q1), with hazard ratios (HRs) and 95% confidence intervals [CIs] of 1.22 (1.13-1.31), 1.13 (1.05-1.22), and 1.26 (1.17-1.36), respectively. Similarly, participants in Q4 of UPF consumption had a higher risk of anxiety, with HRs (95% CIs) of 1.13 (1.06-1.21), 1.13 (1.05-1.21), and 1.11 (1.04-1.19), compared to those in Q1. The study also found a significant association between UPF consumption and all-cause mortality, which disappeared for participants with depression or anxiety. Conclusions: Our findings revealed that UPF consumption is associated with depression or anxiety.

Bidirectional Association Between Multimorbidity and Frailty and the Role of Depression in Older Europeans.

BACKGROUND: Although previous studies have reported an association between multimorbidity and frailty, its direction and mechanism remain unclear. This study aimed to investigate the direction of this association, as well as the role of depression among older Europeans. METHODS: We used a cross-lagged panel design to evaluate the temporal relationship between multimorbidity and frailty and the role of depression. Multimorbidity status was assessed by the self-reporting of 14 chronic diseases. Frailty was assessed based on the frailty phenotype. The European-Depression Scale (EURO-D) was used to assess depression. RESULTS: There was a bidirectional relationship between frailty and multimorbidity. More severe multimorbidity predicted greater frailty (ß = 0.159; p < .001) and vice versa (ß = 0.107; p < .001). All paths from multimorbidity to frailty were stronger than the paths from frailty to multimorbidity (b1-a1: ß = 0.051; p < .001). Likewise, early multimorbidity change was a significant predictive factor for late frailty change (ß = 0.064; p < .001) and vice versa (ß = 0.048; p < .001). Depression in Wave 5 (T5) mediated the association between frailty in Wave 4 (T4) and multimorbidity in Wave 6 (T6; indirect effect: ß = 0.004; bootstrap 95% confidence interval: 0.003, 0.006). CONCLUSIONS: A positive, bidirectional association was observed between multimorbidity and frailty. Depression may be a potential cause of an increased risk of multimorbidity later in life in frail older adults. Early monitoring of frailty and depression may slow the progression of multimorbidity, thereby interrupting the vicious cycle.

Mechanism of the association between sleep quality and mortality in middle-aged and older adults: A prospective study analysis of the UK Biobank.

BACKGROUND: Although sleep quality is known to be associated with mortality, how poor sleep quality contributes to an increased risk of mortality is still unknown. We aimed to examine whether lifestyle, psychosocial and biological factors mediate the association. METHODS: 205,654 participants from UK Biobank were used for the analysis. The outcome was all-cause, cardiovascular disease (CVD) and cancer mortality by February 2022. Exposure was assessed by a sleep score consisting of five sleep behaviors at baseline. Lifestyle, psychosocial, and biological factors are regarded as potential mediators. Mediation analysis based on Cox proportional hazards models was performed. RESULTS: Poor sleep quality was associated with a higher risk of all-cause (Hazard Ratio [HR] = 1.098; 95% CI: 1.058-1.140), CVD (HR = 1.139; 95% CI: 1.045-1.243) and cancer mortality (HR = 1.095; 95% CI: 1.040-1.152). Lifestyle mediators (smoking, physical activity, sedentary, BMI and diet) could explain between 2.6% and 34.0% of the increased risk of all-cause mortality in individuals with poor sleep quality. Self-reported health, frailty, depression, and loneliness were significant psychosocial mediators of this association pathway. About one-fifth of the association can be explained by the biological role of CRP. Similar mediating patterns were observed for CVD and cancer mortality. LIMITATIONS: Both exposure and mediators were measured at baseline, so the possibility of reverse causality cannot be ruled out. CONCLUSIONS: Poor sleep quality is associated with an increased risk of death through a combination of lifestyle, psychosocial and biological pathways. Adopting healthy lifestyles and staying psychosocial well-being are cost-effective interventions to lower the risk of death.

Bidirectional Associations Between Sleep Quality and Grip Strength and the Mediating Role of Depression: Evidence From Two Nationally Representative Cohorts.

BACKGROUND: Although studies have demonstrated associations between sleep quality (SQ) and grip strength (GS) in older adults, the direction and underlying mechanisms of this relationship are yet to be better delineated. We aimed to longitudinally investigate the bidirectional association between SQ and GS and the mediating role of depression in this association. METHODS: Based on 2 nationally representative samples with people aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS; 4 200 participants) and English Longitudinal Study of Ageing (ELSA; 5 922 participants), cross-lagged panel models were employed to examine the potential bidirectional relationships between objectively measured GS and self-reported SQ. RESULTS: We observed a GS-SQ bidirectional association dominated by GS. After adjusting for potential confounders, a higher GS at T1 predicted better SQ at T2 (ELSA: ß = 0.075; CHARLS: ß = 0.104, p < .001) and vice versa (ELSA: ß = 0.034; CHARLS: ß = 0.030, p < .01). Moreover, depression partially mediated the impact of GS on subsequent SQ (ELSA, indirect effect: 0.0057, 95% confidence interval [CI]: 0.0035-0.0084; CHARLS, indirect effect: 0.0086, 95% CI: 0.0051, 0.0131), but not vice versa. CONCLUSIONS: The results regarding data from both cohorts consistently supported a bidirectional association between GS and SQ and the mediating role of depression in the dominant pathway of this bidirectional relationship. Older adults with a low GS should be made aware of a potentially vicious cycle related to depression that can affect their sleep. Regular screening for depression may help to break this cycle.

The Longitudinal Association Between Frailty, Cognition, and Quality of Life in Older Europeans.

OBJECTIVES: Evidence on the association between frailty and quality of life (QoL) is mostly limited to cross-sectional studies. Thus, the temporal order and potential mechanisms of this association are largely unknown. Our study examines both the directionality of this association and the role of cognition in this association in longitudinal data. METHODS: Cross-lagged panel models were employed to examine the temporal relationship between frailty and QoL, as well as cognition's role among 19,649 older adults in Europe. Frailty, QoL, and cognition were assessed using the health deficit index, CASP-12, and 3 standard cognitive tests, respectively. RESULTS: We observed a bidirectional association between frailty and QoL and their dynamics. High initial levels of frailty predicted poorer QoL later and vice versa (ß = -0.151 and -0.052, p < .001). The early change in frailty predicted the late change in QoL, and vice versa (ß = -0.093 and -0.061, p < .001). Frailty or its early change drives this interrelationship. Cognition at Wave 5 partially mediated frailty's effect at Wave 4 on QoL at Wave 6 (indirect effect: ß = -0.005, 95% confidence interval = -0.006, -0.004). DISCUSSION: Our findings supported that early prevention of frailty and its risk factors may have more influential protective effects on later physical and mental health, as well as the need for ongoing screening for mental health in aging population. Also, the maintenance of good cognitive performance may help interrupt this possible vicious cycle linking frailty and QoL decline.

Moderated-mediation analysis of multimorbidity and health-related quality of life among the Chinese elderly: The role of functional status and cognitive function.

Objectives: To investigate the relationship between multimorbidity and health-related quality of life (HRQoL), and explore the effects of functional status and cognitive function on Chinses elderly behind this relationship. Methods: The Multivariate logistic regression and Tobit regression models were used to determine the influence of multimorbidity on HRQoL. Bootstrap analysis was used to probe the mediating effects of functional status and the moderating role of cognition on multimorbidity and HRQoL. Results: Results of the 2,887 participants age ≥ 60 years included in the analysis, 51.69% had chronic diseases. Stroke (ß = -0.190; 95% confidence interval [CI], -0.232, -0.149; p < 0.001) and the combination of hypertension and stroke (ß = -0.210; 95% CI, -0.259, -0.160; p < 0.001) had the greatest influence on HRQoL. Functional status partially mediated the relationship between the number of non-communicable diseases (No. of NCDs) and HRQoL, while cognitive function had a moderating effect not only in the A-path (No. of NCDs to functional status, ß = 0.143; t = 7.18; p < 0.001) and but also in the C-path (No. of NCDs to HRQoL, ß = 0.007; t = 6.08; p < 0.001). Conclusion: Functional status partially mediated the relationship between multimorbidity and HRQoL in older adults. And cognitive function, if declined, may strengthen this relationship. These findings suggested that improving cognitive function and functional status in those who developed multimorbidity could be a viable prevention or treatment strategy to improve HRQoL in elderly patients.

Associations of ultra-processed food consumption with cardiovascular disease and all-cause mortality: UK Biobank.

BACKGROUND: This study aimed to investigate the associations between ultra-processed food (UPF) consumption and the risk of cardiovascular disease and all-cause mortality in the UK Biobank Cohort. METHODS: This observational prospective study evaluated 60 298 participants aged 40 years or older. We used the NOVA classification system to identify and categorize UPF. The associations among UPF consumption, cardiovascular disease (CVD) incidence and all-cause mortality were estimated using multivariable Cox proportional hazards models. Dose-response analysis of UPF consumption and CVD incidence and mortality was performed using a restricted cubic spline. RESULTS: After a median follow-up of 10.9 years, 6048 participants (10.0%) experienced CVD events, and 5327 (8.8%) and 1503 (2.5%) experienced coronary heart and cerebrovascular diseases, respectively. There were 2590 (4.3%) deaths, of which 384 (0.6%) deaths were caused by CVD. A higher intake of UPF was associated with a higher risk of CVD and all-cause mortality (all P < 0.001). A higher intake of UPF was associated with a higher risk of CVD [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.09-1.26], coronary heart disease (HR = 1.16, 95% CI: 1.07-1.25), cerebrovascular disease (HR = 1.30, 95% CI: 1.13-1.50) and all-cause mortality (HR = 1.22, 95% CI: 1.09-1.36). The association of UPF consumption with a range of CVD incidents and all-cause mortality was monotonic (all P for non-linearity > 0.30). CONCLUSIONS: A higher proportion of UPF consumption was associated with CVD and all-cause mortality. Thus, actions to limit UPF consumption should be incorporated into the CVD and all-cause mortality prevention recommendations.

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank.

BACKGROUND AND AIMS: The visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined. METHODS AND RESULTS: In this large-scale prospective epidemiological study, 357,457 participants (aged 38-73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148-1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150-1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148-1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148-1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25. CONCLUSION: In summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.

Cohort profile: the Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study).

PURPOSE: The Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study) is a prospective population-based study which aims to investigate and identify the determinants of the most prevalent chronic non-communicable diseases (NCDs) and to evaluate the impact of demographic characteristics, lifestyle, dietary habits, cognition, disability and NCDs on the health-related quality of life. PARTICIPANTS: Between March 2019 and June 2020, 10 056 individuals aged ≥18 years were administered a baseline survey through a multistage cluster random sampling in Liyang City, southern Jiangsu Province, China. FINDINGS TO DATE: The Liyang Study included detailed sociodemographic, anthropometric and health-related behaviour, common NCDs and blood sample information. Moreover, the study gathered a series of data on specific scales including the activities of daily living, instrumental activities of daily living, abbreviated mental test, Food Frequency Questionnaire and EuroQol 5-Dimensions 5-Levels Scale. Of the 10 056 participants, 52.92% (n=5322) were female and 92.26% (n=9278) came from rural areas. The mean age was 49.9±16.2 years. Men were more likely to have a higher level of education, annual income and a paid job than women (p<0.05). The top three overall most prevalent NCDs in the study were hypertension (18.06%, n=1815), digestive diseases (7.88%, n=791), and arthritis or rheumatism (5.28%, n=530). Women had a significantly higher prevalence of diabetes (5.46%, n=290 vs 4.42%, n=209, p=0.016) and arthritis (6.04%, n=321 vs 4.42%, n=209, p<0.001) than men, while the opposite was true for chronic lung diseases such as chronic obstructive pulmonary disease (1.37%, n=65 vs 0.92%, n=49, p=0.032) and chronic hepatic diseases (0.80%, n=38 vs 0.47%, n=25, p=0.035). FUTURE PLANS: The current study will give valuable insights into the association between sociodemographic factors, health-related behaviour, diet, cognition, disability and genetic factors and the most prevalent NCDs among local community residents. Starting from 2022, a follow-up survey will be conducted every 3 years to further explore the causal relationship between the above factors and NCDs.

The role of depression and physical activity in the association of between sleep quality, and duration with and health-related quality of life among the elderly: a UK Biobank cross-sectional study.

BACKGROUND: Although studies have shown that sleep quality (duration) is associated with health-related quality of life (HRQoL), most of these studies have been small-sized and targeted at young and middle-aged adults. In addition, few studies have explored the path mechanism of sleep disorders leading to impaired HRQoL. OBJECTIVES: This study aimed to determine the association between sleep quality and duration and HRQoL among the elderly in the United Kingdom, assess whether depression mediated the association, and explore the role of physical activity (PA) in the path association. METHODS: Data were extracted from the baseline survey of the UK Biobank, a large prospective cohort study enrolling more than 500,000 participants, of which 52,551 older adults (aged ≥60 years) were included in the study. HRQoL was assessed using the European Quality of Life-5 Dimensions. Tobit and multivariate logistic regression models were used to determine the association between sleep quality and duration and HRQoL. The mediating and moderated mediation models were estimated using the PROCESS macro and MEDCURVE macro. RESULTS: The Tobit model showed that the elderly with short or long sleep duration (ß = - 0.062, 95% confidence interval [CI] = - 0.071 to - 0.053; ß = - 0.072, 95% CI = - 0.086 to - 0.058) had worse HRQoL after adjusting potential covariates. In the logistic regression models, we found an inverted U-shaped association between sleep duration and HRQoL. Moreover, a significant positive association was observed between sleep quality and HRQoL (all P < 0.05). The results also revealed that depression mediated the association between sleep disorders and HRQoL (sleep quality: ß = 0.008, 95% CI = 0.007-0.010; sleep duration: θ = 0.001 [mean], 95% CI = 0.001-0.002). Furthermore, PA moderated all paths among sleep quality and duration, depression, and HRQoL, and greater effects were observed in the elderly with lower PA levels. CONCLUSIONS: The findings show that poor sleep quality and duration were independently associated with worse HRQoL among the elderly in the United Kingdom. Furthermore, PA buffers the mediating effect of depression and adverse effects of sleep disorders on HRQoL. It is essential to properly increase PA and provide early intervention for depression in the elderly with sleep disorders to improve their HRQoL.

The main mechanisms of trimethyltin chloride-induced neurotoxicity: Energy metabolism disorder and peroxidation damage.

Trimethyltin chloride (TMT) is a by-product in the synthesis of organotin, a plastic stabilizer. With the rapid development of industry, the occupational hazards caused by TMT cannot be ignored. TMT is a typical neurotoxicant, which mainly damages the limbic system and brainstem of the nervous system. Previous studies have demonstrated that the neurotoxicity induced by TMT is linked to the inhibition of energy metabolism, but the underlying mechanism remains elusive. In order to investigate the mechanism of TMT-induced inhibition of energy metabolism, C57BL/6 male mice were administered by IP injection in different TMT doses (0 mg/kg, 1.00 mg/kg, 2.15 mg/kg and 4.64 mg/kg) and times (1d, 3d and 6d), and then the changes of superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Na+-K+-ATPase activity in cerebral cortex, cerebellum, hippocampus, pons, medulla oblongata of mice, the expressions of Na+-K+-ATPase protein, AMP-activated protein kinase (AMPK), phosphorylated AMP-activated protein kinase(p-AMPK)and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) in hippocampus and medulla oblongata were measured; the effects of TMT on the viability, the activity of SOD, glutathione (GSH) and Na+-K+-ATPase, MDA level, and the expression of PGC-1α and Na+-K+-ATPase protein in N2a cells were measured by different TMT doses and times, in order to verify the experiments in vivo. Our results found that most of the mice showed depression, tremor, epilepsy, spasm and other symptoms after TMT exposure. Moreover, with the increase of TMT dose, the activity of Na+-K+-ATPase and the expressions of AMPK protein in the hippocampus and medulla oblongata of mice decreased, and the expressions of p-AMPK protein increased. Peroxidative damage was evident in hippocampus, medulla oblongata of mice and N2a cells, and the expression of PGC-1α and Na+-K+-ATPase protein was significantly down-regulated. Therefore, it is reasonable to believe that TMT-induced neurotoxic symptoms and inhibition of energy metabolism may be related to p-AMPK and down-regulation of PGC-1α in the hippocampus and medulla oblongata.

An improved approach for studying oscillation of second-order neutral delay differential equations.

The paper is devoted to the study of oscillation of solutions to a class of second-order half-linear neutral differential equations with delayed arguments. New oscillation criteria are established, and they essentially improve the well-known results reported in the literature, including those for non-neutral differential equations. The adopted approach refines the classical Riccati transformation technique by taking into account such part of the overall impact of the delay that has been neglected in the earlier results. The effectiveness of the obtained criteria is illustrated via examples.