Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

A general strategy to generate oxygen vacancies in bimetallic layered double hydroxides for water oxidation.

A general electrocatalyst design for water splitting through generating oxygen vacancies in bimetallic layered double hydroxides by using carbon nitride is proposed. The excellent OER activity of the achieved bimetallic layered double hydroxides is attributed to oxygen vacancies, which reduce the energy barrier of the rate-determining step.

Simulation of slip transients and earthquakes in finite thickness shear zones with a plastic formulation.

We perform numerical experiments of damped quasi-dynamic fault slip that include a rate-and-state behavior at steady state to simulate earthquakes and a plastic rheology to model permanent strain. The model shear zone has a finite width which represents a natural fault zone. Here we reproduce fast and slow events that follow theoretical and observational scaling relationships for earthquakes and slow slip events (SSEs). We show that the transition between fast and slow slip occurs when the friction drop in the shear zone is equal to a critical value, Δµc. With lower friction drops, SSEs use nearly all of mechanical work to accumulate inelastic strain, while with higher friction drops fast slips use some of the mechanical work to slip frictionally. Our new formulation replaces the state evolution of rate and state by the stress evolution concurrent with accumulation of permanent damage in and around a fault zone.

Elasticity of Ferropericlase across the Spin Crossover in the Earth's Lower Mantle.

Knowing the elasticity of ferropericlase across the spin transition can help explain seismic and mineralogical models of the lower-mantle including the origin of seismic heterogeneities in the middle to lowermost parts of the lower mantle. However, the effects of spin transition on full elastic constants of ferropericlase remain experimentally controversial due to technical challenges in directly measuring sound velocities under lower-mantle conditions. Here we have reliably measured both VP and VS of a single-crystal ferropericlase ((Mg0.92,Fe0.08)O) using complementary Brillouin Light Scattering and Impulsive Stimulated Light Scattering coupled with a diamond anvil cell up to 96 GPa. The derived elastic constants show drastically softened C11 and C12 within the spin transition at 40-60 GPa while C44 is not affected. The spin transition is associated with a significant reduction of the aggregate VP/VS via the aggregate VP softening because VS softening does not visibly occur within the transition. Based on thermoelastic modelling along an expected geotherm, the spin crossover in ferropericlase can contribute to 2% reduction in VP/VS in a pyrolite mineralogical model in mid lower-mantle. Our results imply that the middle to lowermost parts of the lower-mantle would exhibit enhanced seismic heterogeneities due to the occurrence of the mixed-spin and low-spin ferropericlase.

Consumption of fruit and vegetable and risk of coronary heart disease: a meta-analysis of prospective cohort studies.

BACKGROUND: Observational studies suggest that an association between fruit and vegetable consumption and coronary heart disease (CHD). However, the results are inconsistent. We conducted a meta-analysis to evaluate the relationship of fruit and vegetable consumption with CHD risk and quality the dose-response relationship between them. METHODS: Relevant prospective studies were identified by a search of PubMed, Embase and Web of Science databases to July 2014. A random-effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI). RESULTS: Twenty-three studies involving 937,665 participants and 18,047 patients with CHD were included. Compared with the lowest consumption levels of total fruit and vegetable, fruit and vegetable, the RR of CHD was 0.84 (95% CI, 0.79-0.90), 0.86 (95% CI, 0.82-0.91), 0.87 (95% CI, 0.81-0.93), respectively. The dose-response analysis indicated that, the RR of CHD was 0.88 (95% CI: 0.85-0.91) per 477 g/day of total fruit and vegetable consumption, 0.84 (95% CI: 0.75-0.93) per 300 g/day of fruit intake and 0.82 (95% CI: 0.73-0.92) per 400 g/day of vegetable consumption. A nonlinear association of CHD risk with fruit or vegetable consumption separately was found (P for nonlinearity <0.001). In the subgroup analysis of location, a significant inverse association was observed in Western populations, but not in Asian populations. CONCLUSIONS: This meta-analysis indicates that total fruit and vegetable, fruit and vegetable consumption, are significantly associated with a lower risk of CHD. The significant inverse association was found in Western populations, but not in Asian populations, which warrants further research.

Breakfast skipping and the risk of type 2 diabetes: a meta-analysis of observational studies.

OBJECTIVE: Breakfast skipping has been reported to be associated with type 2 diabetes (T2D), but the results are inconsistent. No meta-analyses have applied quantitative techniques to compute summary risk estimates. The present study aimed to conduct a meta-analysis of observational studies summarizing the evidence on the association between breakfast skipping and the risk of T2D. DESIGN: Systematic review and meta-analysis. SETTING: Relevant studies were identified by a search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) and SINOMED up to 9 August 2014. We also reviewed reference lists from retrieved articles. We included studies that reported risk estimates (including relative risks, odds ratios and hazard ratios) with 95% confidence intervals for the association between breakfast skipping and the risk of T2D. SUBJECTS: Eight studies involving 106,935 participants and 7419 patients with T2D were included in the meta-analysis. RESULTS: A pooled adjusted relative risk for the association between exposure to breakfast skipping and T2D risk was 1·21 (95% CI 1·12, 1·31; P=0·984; I² =0·0%) in cohort studies and the pooled OR was 1·15 (95% CI, 1·05, 1·24; P=0·770; I² =0·0%) in cross-sectional studies. Visual inspection of a funnel plot and Begg's test indicated no evidence of publication bias. CONCLUSIONS: Breakfast skipping is associated with a significantly increased risk of T2D. Regular breakfast consumption is potentially important for the prevention of T2D.

Shift work and diabetes mellitus: a meta-analysis of observational studies.

BACKGROUND: Observational studies suggest that shift work may be associated with diabetes mellitus (DM). However, the results are inconsistent. No systematic reviews have applied quantitative techniques to compute summary risk estimates. OBJECTIVES: To conduct a meta-analysis of observational studies assessing the association between shift work and the risk of DM. METHODS: Relevant studies were identified by a search of PubMed, Embase, Web of Science and ProQuest Dissertation and Theses databases to April 2014. We also reviewed reference lists from retrieved articles. We included observational studies that reported OR with 95% CIs for the association between shift work and the risk of DM. Two authors independently extracted data and assessed the study quality. RESULTS: Twelve studies with 28 independent reports involving 226 652 participants and 14 595 patients with DM were included. A pooled adjusted OR for the association between ever exposure to shift work and DM risk was 1.09 (95% CI 1.05 to 1.12; p=0.014; I(2)=40.9%). Subgroup analyses suggested a stronger association between shift work and DM for men (OR=1.37, 95% CI 1.20 to 1.56) than for women (OR=1.09, 95% CI 1.04 to 1.14) (p for interaction=0.01). All shift work schedules with the exception of mixed shifts and evening shifts were associated with a statistically higher risk of DM than normal daytime schedules, and the difference among those shift work schedules was significant (p for interaction=0.04). CONCLUSIONS: Shift work is associated with an increased risk of DM. The increase was significantly higher among men and the rotating shift group, which warrants further studies.

Determinants of initial utilization of community healthcare services among patients with major non-communicable chronic diseases in South China.

BACKGROUND: Although expected to act as gate-keeping primary care providers, as community health service (CHS) facilities are severely under-utilized; Chinese people in both rural and urban areas used predominantly higher-tier facilities for primary care purpose, with significant financial and outcome consequences. This study intends to explore the determinants of initial utilization of CHS among patients with major non-communicable chronic diseases (NCDs) in order to understand the care-seeking behavior among urban and rural residents in South China. METHODS: A multi-stage cluster random sampling methodology was adopted to create a sample of 19,466 adults with NCDs from 7,970 urban households and 32,035 adults with NCDs from 3,860 rural households in Guangdong, China. Interviews and physical examinations were conducted in 2010 to collect data on patient characteristics, medical conditions, and awareness and utilization of healthcare. Descriptive analysis and logistic regression analysis were performed to study utilization patterns and the factors associated with the patterns. RESULTS: Prevalence of major NCDs in urban areas was significantly higher than that in rural areas (12.55% vs. 8.70%; p<0.001). Second-tier district hospitals were most preferred for initial consultation (46.05% in rural areas vs. 45.32% in urban areas; p<0.001), followed by tertiary general or specialized hospitals (28.39% in rural areas vs. 33.89% in urban areas; p<0.001). The proportion of patients who had initial use of CHS was relatively low (25.56% in rural areas vs. 20.79% in urban areas; p<0.001). Awareness of self-care and the presence of medical insurance were leading factors associated with first contact of CHS facilities in both urban and rural areas. CONCLUSION: The study suggests that CHS facilities are not often used as the first contact for patients in both rural and urban areas in south China. Much effect must be made to enhance the gatekeeper system and improve medical insurance coverage in future healthcare reforms.

Depression and the risk of coronary heart disease: a meta-analysis of prospective cohort studies.

BACKGROUND: Several systematic reviews and meta-analyses demonstrated the association between depression and the risk of coronary heart disease (CHD), but the previous reviews had some limitations. Moreover, a number of additional studies have been published since the publication of these reviews. We conducted an updated meta-analysis of prospective studies to assess the association between depression and the risk of CHD. METHODS: Relevant prospective studies investigating the association between depression and CHD were retrieved from the PubMed, Embase, Web of Science search (up to April 2014) and from reviewing reference lists of obtained articles. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. RESULTS: Thirty prospective cohort studies with 40 independent reports met the inclusion criteria. These groups included 893,850 participants (59,062 CHD cases) during a follow-up duration ranging from 2 to 37 years. The pooled relative risks (RRs) were 1.30 (95% CI, 1.22-1.40) for CHD and 1.30 (95% CI, 1.18-1.44) for myocardial infarction (MI). In the subgroup analysis by follow-up duration, the RR of CHD was 1.36 (95% CI, 1.24-1.49) for less than 15 years follow-up, and 1.09 (95% CI, 0.96-1.23) for equal to or more than 15 years follow-up. Potential publication bias may exist, but correction for this bias using trim-and-fill method did not alter the combined risk estimate substantially. CONCLUSIONS: The results of our meta-analysis suggest that depression is independently associated with a significantly increased risk of CHD and MI, which may have implications for CHD etiological research and psychological medicine.

Prevalence of anxiety and depressive symptoms and related risk factors among physicians in China: a cross-sectional study.

BACKGROUND: Physicians' poor mental health not only hinders their professional performance and affects the quality of healthcare provided but also adversely affects patients' health outcomes. Few studies in China have evaluated the mental health of physicians. The purposes of this study are to quantify Chinese physicians' anxiety and depressive symptoms as well as evaluate associated risk factors. METHODS: In our study, 2641 physicians working in public hospitals in Shenzhen in southern China were recruited and interviewed by using a structured questionnaire along with validated scales testing anxiety and depressive symptoms. Multivariable logistic regression models were used to identify risk factors for anxiety and depressive symptoms. RESULTS: An estimated 25.67% of physicians had anxiety symptoms, 28.13% had depressive symptoms, and 19.01% had both anxiety and depressive symptoms. More than 10% of the participants often experienced workplace violence and 63.17% sometimes encountered it. Among our study population, anxiety and depressive symptoms were associated with poor self-reported physical health, frequent workplace violence, lengthy working hours (more than 60 hours a week), frequent night shifts (twice or more per week), and lack of regular physical exercise. CONCLUSIONS: Our study demonstrates that anxiety and depressive symptoms are common among physicians in China, and the doctor-patient relationship issue is particularly stressful. Interventions implemented to minimize workload, improve doctor-patient relationships, and assist physicians in developing healthier lifestyles are essential to combat anxiety and depressive symptoms among physicians, which may improve their professional performance.

Construction of the pharmacophore model of acetylcholinesterase inhibitor.

Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.