Increased Levels of Urine Volatile Organic Compounds Are Associated With Diabetes Risk and Impaired Glucose Homeostasis.

CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the effect of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation. OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population. METHODS: Urinary concentrations of VOC metabolites were obtained from the National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOC mixtures. RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOC metabolites showed positive associations with diabetes mellitus (OR, 1.15-1.43; all P < .05), insulin resistance (IR) (OR, 1.02-1.06; P < .05), and other glucose homeostasis indicators (ß, 0.04-2.32; all P < .05). Mixed VOC models revealed positive correlations between the WQS indices and diabetes risk (OR = 1.52; 95% CI, 1.29-1.81), IR (OR = 1.36; 95% CI, 1.14-1.62), and other glucose homeostasis indicators (ß, 0.17-2.22; all P < .05). CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.

Angioplasty for dysfunctional arteriovenous fistulas: A meta-analysis of recent randomized controlled trials compared paclitaxel-coated balloon versus conventional balloon angioplasty.

BACKGROUND: Stenosis in arteriovenous fistulas (AVF) due to neointimal hyperplasia is one of the most common causes of hemodialysis vascular access dysfunction. Treating patients with dysfunctional AVF with drug-coated balloon (DCB) angioplasty may potentially improve outcomes. OBJECTIVES: This systematic review aimed to compare the effectiveness and safety of DCB angioplasty versus conventional balloon angioplasty by pooling evidence from the most recent randomized controlled trials. METHODS: We conducted a comprehensive literature search in the Web of Science, Embase, and Cochrane central databases. Two independent researchers screened the article, extracted interest, and evaluated included studies for risk of bias. Pooled estimation was conducted in terms of 6-month target-lesion primary patency (TLPP) and target-lesion reintervention (TLR), as well as other outcomes. RESULTS: Results were expressed with odds ratio (OR) and 95% confidence interval (CI). A total of five RCTs were identified and included in the meta-analyses, with 1107 participants. DCB has a trend of a higher rate of TLPP (OR 1.79, 95% CI 0.66-4.90, p = 0.181) and a significantly lower rate of TLR (0.52, 95% CI 0.29-0.92, p = 0.034), as compared to conventional balloon angioplasty. No difference in the 6-month access circuit primary patency and reinvention was observed between the two groups. CONCLUSION: DCB may be an alternative treatment of dysfunctional AVF given a trend of a higher rate of TLPP and a significantly lower rate of TLR than conventional balloon angioplasty within 6 months after the indexed procedure. Moreover, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Considering variations in the DCB technique, further studies are warranted for a standardized process.

Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study.

INTRODUCTION: Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors. METHODS AND ANALYSIS: This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR. ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.

Association of cholecystectomy with osteoporosis risk: a prospective study using data from the UK Biobank.

Objective: To investigate whether prior cholecystectomy is associated with incident osteoporosis. Background: Cholecystectomy may have consequences involving abnormal metabolism. Studies investigating the association between prior cholecystectomy and osteoporosis have yielded inconsistent results. Methods: In total, 17,603 UK Biobank participants underwent cholecystectomy, and 35,206 matched controls were included in this study. They were followed up for incident osteoporosis, which was determined using ICD-10 codes (M80-82). The association between cholecystectomy and osteoporosis was assessed using Cox proportional regression modeling. The association between osteoporosis risk and cholecystectomy was further analyzed across age, sex, serum vitamin D level, and body mass index (BMI) categories. Results: Within a median follow-up period of 13.56 years, 3,217 participants were diagnosed with osteoporosis. After adjustment for relevant confounders, prior cholecystectomy was associated with a 1.21 times higher risk of osteoporosis in women (hazard ratio (HR): 1.21 [95% CI, 1.12-1.31], p < 0.001) and a 1.45 times higher risk in men (HR: 1.45 [95% CI, 1.10-1.90], p = 0.007). In women, the association was stronger for patients who were aged 40-55 years, with BMI < 18.5 kg/m2, and vitamin D between 30 and 50 nmol/ml. No significant interactions between cholecystectomy and income level, education level, presence of hypertension, or diabetes were identified in either sex. Conclusions: Our findings indicated that people who underwent cholecystectomy had a higher risk of developing osteoporosis after adjustment for potential confounders. Our findings suggest that awareness of the risk of osteoporosis in patients with a history of cholecystectomy is merited.

Association of B vitamin intake and total homocysteine levels with all-cause and cause-specific mortality in central obesity.

OBJECTIVES: Future primary prevention strategies may benefit from understanding the connection between mortality in individuals with central obesity and modifiable lifestyle factors like dietary intake. This study sought to determine whether there was a separate relationship between folate, vitamin B6, and vitamin B12 intake and all-cause and cause-specific mortality in the US population with central obesity. METHODS: The study analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2016. Using the Cox proportional hazards model, the association between dietary intake of B vitamins and all-cause and cause-specific mortality was examined. A total of 7718 adults with central obesity were enrolled, with a mean age of 49.87 (SD = 0.25) y at baseline. RESULTS: Folate intake was independently associated with a decreased incidence of all-cause mortality (adjusted hazard ratio = 0.71; 95% CI, 0.58-0.87). Furthermore, higher intake of vitamin B6 and vitamin B12 was inversely correlated with cardiovascular disease mortality (adjusted hazard ratio = 0.63; 95% CI, 0.40-0.98; and adjusted hazard ratio = 0.44; 95% CI, 0.29-0.65, respectively) and the finding reveal an interaction between homocysteine and vitamin B12 and folate on All-cause mortality CONCLUSIONS: The findings of this study suggest that vitamin B12 and folate intake may be protective factors in individuals with central obesity. It is important to consider both their total homocysteine level and body mass index in conjunction with these nutrients. Further research is needed to validate these findings.

Transferring From Textual Entailment to Biomedical Named Entity Recognition.

Biomedical Named Entity Recognition (BioNER) aims at identifying biomedical entities such as genes, proteins, diseases, and chemical compounds in the given textual data. However, due to the issues of ethics, privacy, and high specialization of biomedical data, BioNER suffers from the more severe problem of lacking in quality labeled data than the general domain especially for the token-level. Facing the extremely limited labeled biomedical data, this work studies the problem of gazetteer-based BioNER, which aims at building a BioNER system from scratch. It needs to identify the entities in the given sentences when we have zero token-level annotations for training. Previous works usually use sequential labeling models to solve the NER or BioNER task and obtain weakly labeled data from gazetteers when we don't have full annotations. However, these labeled data are quite noisy since we need the labels for each token and the entity coverage of the gazetteers is limited. Here we propose to formulate the BioNER task as a Textual Entailment problem and solve the task via Textual Entailment with Dynamic Contrastive learning (TEDC). TEDC not only alleviates the noisy labeling issue, but also transfers the knowledge from pre-trained textual entailment models. Additionally, the dynamic contrastive learning framework contrasts the entities and non-entities in the same sentence and improves the model's discrimination ability. Experiments on two real-world biomedical datasets show that TEDC can achieve state-of-the-art performance for gazetteer-based BioNER.

Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population.

AIMS: To evaluate the ability of Systematic COronary Risk Estimation 2 (SCORE2) and other pre-screening methods to identify individuals with high coronary artery calcium score (CACS) in the general population. METHODS AND RESULTS: Computed tomography-based CACS quantification was performed in 6530 individuals aged 45 years or older from the general population. Various pre-screening methods to guide referral for CACS were evaluated. Miss rates for high CACS (CACS ≥300 and ≥100) were evaluated for various pre-screening methods: moderate (≥5%) and high (≥10%) SCORE2 risk, any traditional coronary artery disease (CAD) risk factor, any Risk Or Benefit IN Screening for CArdiovascular Disease (ROBINSCA) risk factor, and moderately (>3 mg/24 h) increased urine albumin excretion (UAE). Out of 6530 participants, 643 (9.8%) had CACS ≥300 and 1236 (18.9%) had CACS ≥100. For CACS ≥300 and CACS ≥100, miss rate was 32 and 41% for pre-screening by moderate (≥5%) SCORE2 risk and 81 and 87% for high (≥10%) SCORE2 risk, respectively. For CACS ≥300 and CACS ≥100, miss rate was 8 and 11% for pre-screening by at least one CAD risk factor, 24 and 25% for at least one ROBINSCA risk factor, and 67 and 67% for moderately increased UAE, respectively. CONCLUSION: Many individuals with high CACS in the general population are left unidentified when only performing CACS in case of at least moderate (≥5%) SCORE2, which closely resembles current clinical practice. Less stringent pre-screening by presence of at least one CAD risk factor to guide CACS identifies more individuals with high CACS and could improve CAD prevention.

Association of serum levels of calcium, phosphate, and vitamin D with risk of developing aortic stenosis: the UK Biobank cohort.

AIMS: This study was aimed to investigate the associations of serum calcium, phosphate, and vitamin D levels with the risk of developing aortic stenosis (AS). METHODS AND RESULTS: We included 296 415 participants who were free of prior diagnosis of any valvular heart disease from the UK Biobank. Serum levels of phosphate, calcium, and vitamin D were measured. Incidental AS was determined by the records of hospital data. Cox regression was used to examine the association of serum mineral levels with incidental AS after adjustment for potential confounders. The mean age was 56.4 years (SD 8.14) and 53.3% of participants were women. During an average follow-up of 8.1 years, 1232 individuals developed AS. After adjustment, each 0.5-unit increase in serum phosphate level was associated with a 50% increase of AS risk (hazard ratio 1.50, 95% confidence interval 1.26-1.80). We observed no association of serum calcium and vitamin D levels with AS. CONCLUSION: Increased serum phosphate level, but not calcium or vitamin D, was associated with a higher risk of incident AS, this association did not differed substantially between patients with and without decreased kidney function. This finding implied that phosphate may be a potential interventional target for AS.

The Safety and Necessity of Concomitant Cholecystectomy During Bariatric Surgery in Patients with Obesity: a Systematic Review and Meta-analysis.

Concomitant cholecystectomy (CCE) during bariatric surgery(BS)in patients with obesity remains a matter of debate. This study aimed to estimate the safety and necessity of CCE during BS. This study analyzed the postoperative complications in patients who underwent CCE during BS and subsequent cholecystectomy rate following BS. Patients in CCE and BS-only groups had no difference in mortality. A higher postoperative complication rate was observed in the CCE group (OR 1.2, 95% CI 1.1-1.3) (p < 0.001) but no severe complication in both groups. Following BS, gallstone patients had a higher subsequent cholecystectomy rate than those with normal gallbladders (OR 2.47%, 95% CI 1.5-4.1) (p < 0.001). Concomitant cholecystectomy increased the rates of postoperative complications during BS. We only recommend CCE for documented gallstones rather than for normal gallbladder.

Angiotensin-converting enzyme inhibitor for post-transcatheter aortic valve implantation patients: study protocol for a multicenter randomized, open-label blinded endpoint control trial.

BACKGROUND: With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. METHODS: A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. DISCUSSION: This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021.

In Vitro and In Vivo Comparative Evaluation of a Shellac-Ammonium Paclitaxel-Coated Balloon versus a Benchmark Device.

OBJECTIVES: The present study was designed to compare the characteristics and performance regarding drug delivery of a novel drug-coated balloon (DCB) to a benchmark device (Restore® versus SeQuent® Please) in an in vitro and in vivo model. BACKGROUND: Although Restore® and SeQuent® are both paclitaxel-coated, they use different coating excipient, shellac-ammonium salt and iopromide, respectively. Preclinical study comparing these two different commercial DCBs regarding their characteristics and effects on early vascular response is sparse. METHODS: Restore® and SeQuent® DCBs were scanned with electron microscopy for surface characteristic assessment. Both DCBs were transported in an in vitro vessel model for the evaluation of drug wash-off rate and particulate formation. Eighteen coronary angioplasties with either Restore® or SeQuent® DCBs were conducted in 6 swine (three coronary vessels each). Histopathological images of each vessel were evaluated for vessel injury. RESULTS: The surface of Restore® DCB was smooth and evenly distributed with hardly visible crystal, while SeQuent® DCB showed a rougher surface with relatively larger apparent crystals. Restore® DCB had a lower drug wash-off rate and fewer large visible particles, compared to the SeQuent® DCB. No significant difference in mean injure score was found between Restore® and SeQuent® group. CONCLUSION: Our results suggest that Restore® is better in preclinical performance regarding less release of particles and lower drug wash-off rate as compared to SeQuent® Please. The Restore® DCB, using stable amorphous coating and shellac-ammonium salt as an excipient, appears to provide an advantage in drug delivery efficacy; however, further clinical studies are warranted.

Coronary Artery Calcium and Cognitive Function in Dutch Adults: Cross-Sectional Results of the Population-Based ImaLife Study.

Background The aim of this study was to investigate whether increased severity of coronary artery calcium (CAC), an imaging biomarker of subclinical coronary atherosclerosis, is associated with worse cognitive function independent of cardiovascular risk factors in a large population-based Dutch cohort with broad age range. Methods and Results A cross-sectional analysis was performed in 4988 ImaLife participants (aged 45-91 years, 58.3% women) without history of cardiovascular disease. CAC scores were obtained using nonenhanced cardiac computed tomography scanning. The CogState Brief Battery was used to assess 4 cognitive domains: processing speed, attention, working memory, and visual learning based on detection task, identification task, 1-back task, and 1-card-learning task, respectively. Differences in mean scores of each cognitive domain were compared among 4 CAC categories (0, 1-99, 100-399, ≥400) using analysis of covariates to adjust for classical cardiovascular risk factors. Age-stratified analysis (45-54, 55-64, and ≥65 years) was performed to assess whether the association of CAC severity with cognitive function differed by age. Overall, higher CAC was associated with worse performance on 1-back task after adjusting for classical cardiovascular risk factors, but CAC was not associated with the other cognitive tasks. Age-stratified analyses revealed that the association of CAC severity with working memory persisted in participants aged 45 to 54 years, while in the elderly this association lost significance. Conclusions In this Dutch population of ≥45 years, increased CAC severity was associated with worse performance of working memory, independent of classical cardiovascular risk factors. The inverse relationship of CAC score categories with working memory was strongest in participants aged 45 to 54 years.

Cardiovascular Risk Factors and Coronary Calcification in a Middle-aged Dutch Population: The ImaLife Study.

PURPOSE: To assess the presence of coronary artery calcium (CAC) and its association with cardiovascular risk factors and Systematic COronary Risk Evaluation (SCORE) risk in a middle-aged Dutch population. METHODS: Classic cardiovascular risk factors and CAC were analyzed in 4083 participants aged 45 to 60 years (57.9% women) from the population-based ImaLife study. CAC scores were quantified on noncontrast cardiac CT scans. Age-specific and sex-specific distribution of CAC categories (0, 1 to 99, 100 to 299, ≥300) and percentiles were determined. SCORE risk categories (<1%, ≥1% to 5%, and ≥5%) were compared with CAC distribution. Population attributable fractions (PAFs) of classic risk factors for CAC were estimated. RESULTS: CAC was present in 54.5% male and 26.5% female participants. The percentage of individuals with CAC increased with increasing age. Mean SCORE was 2.0% in men and 0.7% in women. In SCORE <1%, 32.7% of men and 17.1% of women had CAC. In men with SCORE ≥5%, 26.9% had no CAC. Only 0.1% of women had SCORE ≥5%. PAF of classic risk factors for CAC was 18.5% in men and 31.4% in women. PAF was highest for hypertension (in men 8.0%, 95% confidence interval, 4.2%-11.8%; in women 13.1%, 95% confidence interval, 7.9%-18.2%) followed by hypercholesterolemia and obesity. CONCLUSION: In this middle-aged cohort, more than half of the men and a quarter of the women had CAC. One out of 4 men at high risk (SCORE ≥5%) could be placed into a lower risk category owing to absence of CAC. Thus, adding CAC scoring to SCORE could have considerable effect on cardiovascular risk classification. Elimination of exposure to classic risk factors could reduce limited proportion of CAC in a middle-aged population.

High-pitch dual-source CT for coronary artery calcium scoring: A head-to-head comparison of non-triggered chest versus triggered cardiac acquisition.

BACKGROUND: To determine the effect of low-dose, high-pitch non-electrocardiographic (ECG)-triggered chest CT on coronary artery calcium (CAC) detection, quantification and risk stratification, compared to ECG-triggered cardiac CT. METHODS: We selected 1,000 participants from the ImaLife study, 50% with coronary calcification on cardiac CT. All participants underwent non-contrast cardiac CT followed by chest CT using third-generation dual-source technology. Reconstruction settings were equal for both acquisitions. CAC scores were determined by Agatston's method, and divided dichotomously (0, >0), and into risk categories (0, 1-99, 100-399, ≥400). We investigated the influence of heart rate and body mass index (BMI) on risk reclassification. RESULTS: Positive CAC scores on cardiac CT ranged from 1 to 6926 (median 39). Compared to cardiac CT, chest CT had sensitivity of 0.96 (95%CI 0.94-0.98) and specificity of 0.99 (95%CI 0.97-0.99) for CAC detection (κ = 0.95). In participants with coronary calcification on cardiac CT, CAC score on chest CT was lower than on cardiac CT (median 30 versus 40, p˂0.001). Agreement in CAC-based risk strata was excellent (weighted κ = 0.95). Sixty-five cases (6.5%) were reclassified by one risk category in chest CT, with fifty-five (84.6%) shifting downward. Higher BMI resulted in higher reclassification rate (13% for BMI ≥30 versus 5.2% for BMI <30, p = 0.001), but there was no effect of heart rate. CONCLUSION: Low-dose, high-pitch chest CT, using third-generation dual-source technology shows almost perfect agreement with cardiac CT in CAC detection and risk stratification. However, low-dose chest CT mainly underestimates the CAC score as compared to cardiac CT, and results in inaccurate risk categorization in BMI ≥30.

Deep learning for automated exclusion of cardiac CT examinations negative for coronary artery calcium.

PURPOSE: Coronary artery calcium (CAC) score has shown to be an accurate predictor of future cardiovascular events. Early detection by CAC scoring might reduce the number of deaths by cardiovascular disease (CVD). Automatically excluding scans which test negative for CAC could significantly reduce the workload of radiologists. We propose an algorithm that both excludes negative scans and segments the CAC. METHOD: The training and internal validation data were collected from the ROBINSCA study. The external validation data were collected from the ImaLife study. Both contain annotated low-dose non-contrast cardiac CT scans. 60 scans of participants were used for training and 2 sets of 50 CT scans of participants without CAC and 50 CT scans of participants with an Agatston score between 10 and 20 were collected for both internal and external validation. The effect of dilated convolutional layers was tested by using 2 CNN architectures. We used the patient-level accuracy as metric for assessing the accuracy of our pipeline for detection of CAC and the Dice coefficient score as metric for the segmentation of CAC. RESULTS: Of the 50 negative cases in the internal and external validation set, 62 % and 86 % were classified correctly, respectively. There were no false negative predictions. For the segmentation task, Dice Coefficient scores of 0.63 and 0.84 were achieved for the internal and external validation datasets, respectively. CONCLUSIONS: Our algorithm excluded 86 % of all scans without CAC. Radiologists might need to spend less time on participants without CAC and could spend more time on participants that need their attention.

The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function: A Systematic Review and Meta-Analysis.

AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.

Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study.

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality.

Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i.p.) and myocardial function was assessed 6 h later using echocardiography and hemodynamics. Deteriorated cardiac function evidenced by reduction of the percentage of left ventricular ejection fraction and fractional shortening after LPS administration was significantly attenuated by cardiomyocyte specific expression of ACOT1. αMHC-ACOT1 mice exhibited a markedly increase in glucose utilization and cardiac FAO compared with LPS-treated WT mice. Suppression of cardiac peroxisome proliferator activated receptor alpha (PPARa) and PPARγ-coactivator-1α (PGC1a) signaling observed in LPS-challenged WT mice was activated by the presence of ACOT1. These results suggest that ACOT1 has potential therapeutic values to protect heart from sepsis mediated dysfunction, possibly through activating PPARa/PGC1a signaling.

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway.

BACKGROUND/AIMS: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF). However, whether bradykinin can regulate TF expression remains to be investigated. METHODS: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS) to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. RESULTS: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-x03BA;B level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. CONCLUSION: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.