Generation of cylindrical vector modes via astigmatic mode conversion.

In this work, we propose and demonstrate experimentally a compact technique for generating cylindrical vector beams based on a Michelson interferometer and a π-astigmatic mode converter. The latter is required to invert the topological charge of higher-order Laguerre-Gauss (LG) beams. Our proposed technique generalizes the use of astigmatic mode conversion, commonly associated only with scalar beams, to vector beams with a non-homogeneous polarization distribution. We anticipate that many applications based on Michelson interferometers will benefit from the unique properties of vector beams.

Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

BACKGROUND: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. METHODS: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. FINDINGS: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. INTERPRETATION: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community.

How to cite this article: Xiao-Bo H, Poonyathawon S, Semedi BP, Xiao-Yi Z, Wei F, Da-Wei W, et al. International-focused Online Forum: A Good Way to Jointly Manage the COVID-19 Pandemic for Global Critical Care Community. Indian J Crit Care Med 2020;24(4):283-284.

The clinical characteristics of alcohol-related ocular rupture.

PURPOSE: To evaluate the characteristics and outcomes of drunken patients treated for ocular rupture, and to compare these results to patients injured without alcohol consumption. DESIGN AND METHODS: The medical records of 182 patients with or without alcohol consumption before injury who were treated and followed up because of ocular rupture at the Affiliated Hospital of Weifang Medical University from October 2007 to October 2011 were evaluated retrospectively. The characteristics and outcomes of 45 alcohol-related injury patients were compared with the rest in the cohort. The clinical data included in this study were: anatomic sites and length of the wound, involvement of ocular adnexa injuries, evisceration rate, and final mean visual acuity. RESULTS: Wound locations were significantly different between the alcohol-related group and the non-alcohol-related one. Compared with the non-alcohol-related ocular rupture population, the anatomic sites of the drunken patients were more likely to be located at zone I and zone II (60.0 vs 40.1 %; χ2 = 5.39,P < 0.05). The difference of wound length between the alcohol-related group and the non-alcohol-related one was significant. The alcohol-related patients had a longer wound length (Z = -8.590,P < 0.05). Compared with the non-alcohol population, the alcohol-consuming patients were more likely to suffer adnexa injuries (84.4 vs 59.8 %; χ2 = 5.86,P < 0.05), and had worse final visual acuities (Z = -7.195,P < 0.05). The evisceration rate of the alcohol-related patients was significantly higher than the non-alcohol patients (24.4 vs 9.4 %; χ2 = 6.62,P < 0.05). CONCLUSIONS: Drinking more easily leads to injury of the front part of eyes. Moreover, the drunken patients had a worse visual acuity outcome, longer wound length, higher evisceration rate, and were more prone to endure adnexa injuries. The importance of prevention and education to recognize the hazards of drinking cannot be overemphasized.

Apoptosis of human umbilical vein endothelial cells (HUVEC) induced by IgA1 isolated from Henoch-Schonlein purpura children.

OBJECTIVE: It had been shown that apoptosis of vascular endothelial cells played an important role in the pathogenesis of HSP. The present study was designed to investigate the apoptosis of vascular endothelial cells induced by isolated IgA1 from sera of HSP patients. METHODS: HUVEC were cultured in 3 different types of media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by the TUNEL method and flow cytometry, respectively. The expression of bax/bcl-2 and p53 was detected with the methods of Real-time PCR and Westernblot, respectively. RESULT: The results showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than that the normal controls (14.77±2.23% vs 9.97±1.48%) and blank controls (14.77±2.23% vs 2.25±0.77%) (P <0.01). Moreover the rate of HUVEC by IgA1 from normal healthy children was higher than the blank controls (9.97±1.48% vs 2.25±0.77%) (P <0.01). In addition, the bax and P53 expression were up-regulated and the Bcl-2 expression was down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24 hours. CONCLUSIONS: These findings suggested that IgA1 from HSP patients could induce the apoptosis of HUVEC, which might be related to the vascular endothelial injury of HSP.

Industrial Metaverse for Smart Manufacturing: Model, Architecture, and Applications.

Smart manufacturing has been transforming toward industrial digitalization integrated with various advanced technologies. Metaverse has been evolving as a next-generation paradigm of a digital space extended and augmented by reality. In the metaverse, users are interconnected for various virtual activities. In consideration of advanced possibilities that may be brought by the metaverse, it is envisioned that industrial metaverse should be integrated into smart manufacturing to upgrade industry for more visible, intelligent and efficient production in the future. Therefore, a conceptual model, named IMverse Model, and novel characteristics of the industrial metaverse for smart manufacturing are proposed in this article. Besides, an industrial metaverse architecture, named IMverse Architecture, is proposed involving several key enabling technologies. Typical innovative applications of the industrial metaverse throughout the whole product life cycle for smart manufacturing are presented with insights. Nonetheless, in prospect of future, the industrial metaverse still faces limitations and is far from implementation. Thus, challenges and open issues of the industrial metaverse for smart manufacturing are discussed, then outlook is provided for further research and application.

Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

The effects of hypothermia on glutamate and γ-aminobutyric acid metabolism during ischemia in monkeys: a repeated-measures ANOVA study.

During an ischemic stroke, the brain releases various factors, including glutamate and γ-aminobutyric acid. Glutamate can cause neurotoxic effects through certain receptors and exacerbate neurological damage, while γ-aminobutyric acid as an inhibitory neurotransmitter can antagonize the excitotoxic effects of glutamate and enhance the tolerance of neurons to ischemia. Therefore, in this study, the content of amino acid neurotransmitters in brain tissue before ischemia, after 10 min of ischemia, hypothermic perfusion, and rewarming were analyzed by high-performance liquid chromatography-UV in an animal model of ischemic stroke generated by blocking the bilateral common carotid arteries of rhesus monkeys. The changes in amino acid neurotransmitters in the rhesus monkey brain during post-ischemia hypothermic perfusion and rewarming were investigated by statistical methods of repeated measures ANOVA, showing that the concentration change of glutamate had not only a temporal factor but also was influenced by temperature, and there was an interaction effect between the two. Time but not temperature affected the change in γ-aminobutyric acid concentration, and there was an interaction effect between the two. Accordingly, hypoperfusion exerts a protective effect during ischemia by inhibiting the release of excitatory amino acid neurotransmitters, while the antagonistic effect of GABA on Glu is not significant.

Why is the air humid during wintertime heavy haze days in Beijing?

Atmospheric humidity has been shown to promote haze formation, but it remains unclear why the air is humid during heavy haze days in winter. Here we combine water vapor isotope measurements with WRF-Chem simulations to elucidate increasing humidity with aggravation of haze during wintertime in urban Beijing. The vapor isotopic analysis in Beijing shows that the combustion-derived water (CDW) constitutes 11.0± 6.2 % of the atmospheric moisture and its fraction in total moisture increases with aggravation of haze. Modeling results reveal that, in addition to the water vapor transported from south or east to Beijing with occurrence of haze, CDW has a considerable impact on the increasing humidity when haze becomes heavy or severe. Aerosol-radiation interactions generally decrease the water vapor content and only increase humidity with occurrence of severe haze with hourly PM2.5 concentrations exceeding 250µg m-3. Although CDW is insignificant in the global atmospheric vapor budget, it could play an important role in modifying the local weather during haze days.

Medications for blood pressure, blood glucose, lipids, and anti-thrombotic medications: relationship with cardiovascular disease and death in adults from 21 high-, middle-, and low-income countries with an elevated body mass index.

AIMS: Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described. METHODS AND RESULTS: We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P < 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to <25 kg/m2, the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications. CONCLUSION: To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI.

Measuring and predicting personal and household Black Carbon levels from 88 communities in eight countries.

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10-5 m-1) of collected PM2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10-5 m-1, respectively. The correlation between BC and PM2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC.

Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study.

OBJECTIVE: To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study. DESIGN: Prospective cohort study. SETTING: PURE study in 21 countries. PARTICIPANTS: 148 858 participants with median follow-up of 9.5 years. EXPOSURES: Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice. MAIN OUTCOME MEASURE: Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre. RESULTS: Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes. CONCLUSION: High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.

Associations of unprocessed and processed meat intake with mortality and cardiovascular disease in 21 countries [Prospective Urban Rural Epidemiology (PURE) Study]: a prospective cohort study.

BACKGROUND: Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent. OBJECTIVE: The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD. METHODS: The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts. RESULTS: In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs. <50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004). CONCLUSIONS: In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

Expression and role of adiponectin receptor 1 in lipopolysaccharide-induced proliferation of cultured rat adventitial fibroblasts.

Adiponectin is an adipose-derived hormone that has anti-diabetic and anti-atherogenic effects through interaction with AdipoR1 and AdipoR2 (adiponectin receptors 1 and 2), but little is known about the expression and function of adiponectin and its receptors in adventitia and adventitial fibroblasts. In the present study, we have demonstrated that AdipoR1 is highly expressed in rat adventitia and cultured adventitial fibroblasts by quantitative real-time PCR, Western blotting and immunofluorescent staining, whereas Adipo2 is low-expressed. The expression of AdipoR1 have been observed to decrease gradually in adventitial fibroblasts in response to LPS (lipopolysaccharide) treatment. No local expression of adiponectin has been detected in adventitial tissues, indicating that serum adiponectin is the ligand for AdipoR1 in adventitial fibroblasts. In addition, treatment of recombinant adiponectin inhibited LPS-induced proliferation of adventitial fibroblasts via activation of the AMPK (adenosine monophosphate-activated protein kinase). AdipoR1 siRNA (small interfering RNA) transfection potently knocked down the receptor protein. The siRNA-AdipoR1 transfected cells and AMPK inhibitor compound C treated cells showed decreased phosphorylated level of AMPK as determined by Western blot analysis, and increased the proliferation of adventitial fibroblasts as determined by BrdU (5-bromo-29-deoxyuridine) staining. These results demonstrated that adiponectin stimulates the proliferation of adventitial fibroblasts via the AdipoR1 and AMPK signalling pathways.

Xenobiotic transcription factors CncC and maf regulate expression of CYP321A16 and CYP332A1 that mediate chlorpyrifos resistance in Spodoptera exigua.

Insect cytochrome P450 s (P450 s) are associated with the metabolic detoxification of toxic xenobiotics and their constitutive upregulation is often associated with resistance to natural and synthetic toxicants. The P450 s CYP321A16 and CYP332A1 are constitutively overexpressed in an insecticide-resistant strain of beet armyworm, Spodoptera exigua. However, the function and upstream regulation of these two P450 s remain unknown. Here, we investigated the function of CYP321A16 and CYP332A1 in resistance to the organophosphate insecticide, chlorpyrifos and their regulation by the transcription factors CncC and Maf. Transgenic strains of Drosophila melanogaster expressing CYP321A16 or CYP332A1 showed higher levels of tolerance to chlorpyrifos than the control flies with the same genetic background. Furthermore, recombinant CYP321A16 and CYP332A1 proteins metabolized chlorpyrifos. Analysis of the putative promoter sequences of the genes coding for CYP321A16 and CYP332A1 revealed conserved CncC/Maf binding sites. Transfection of luciferase reporter plasmids containing the promoter of CYP450 gene together with CncC and Maf expression plasmids significantly enhanced the activity of the reporter. Promoter truncation identified a site in the promoter of CYP321A16 that is critical for the CncC/Maf binding. These data demonstrate that resistance to chlorpyrifos in S. exigua is conferred by the combined action of CYP321A16 and CYP332A1 and uncovered their regulation by the transcription factors CncC and Maf.

Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

Spontaneous recovery of conditioned eyeblink responses is associated with transiently decreased cerebellar theta activity in guinea pigs.

Behavioral studies have demonstrated that extinguished conditioned eyeblink responses (CR) can spontaneously recover after extinction. However, the neural mechanisms underlying this process are still unclear. We have shown that spontaneous cerebellar theta activity was predictive of subsequent CR extinction. Here, we sought to further evaluate the association between spontaneous recovery and cerebellar theta activity in behaving guinea pigs. It was found that trace conditioning training significantly diminished the degree of spontaneous recovery during extinction sessions as compared to delay training. Moreover, by recording local field potential in the cerebellum of guinea pigs undergoing an eyeblink conditioning extinction task, we found that spontaneous recovery of delay-paradigm CRs was associated with transiently decreased CS-evoked theta activity in the cerebellum. These findings suggest that decreased CS-evoked cerebellar theta activity may contribute to the neural process that is important for the spontaneous recovery of extinguished motor memory. Future studies are needed to clarify the neural mechanism underlying changed cerebellar theta activity during altered behavioral contingencies.

Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats.

Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis.

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.