Bestrophin-like protein 4 is involved in photosynthetic acclimation to light fluctuations in Chlamydomonas.

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2-concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid membranes called pyrenoid tubules, which are proposed to deliver CO2. In the model alga Chlamydomonas (Chlamydomonas reinhardtii), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules, and heterologous expression of BST4 in Arabidopsis (Arabidopsis thaliana) did not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonas bst4 mutants did not show impaired growth under continuous light at air level CO2 but were impaired in their growth under fluctuating light. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we propose that bst4 has a transiently lower thylakoid lumenal pH during dark-to-light transition compared to control strains. We conclude that BST4 is not a tethering protein but is most likely a pyrenoid tubule ion channel involved in the ion homeostasis of the lumen with particular importance during light fluctuations.

Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes ATG8-family protein-dependent clearance of MAVS aggregates.

TAX1BP1 is a selective macroautophagy/autophagy receptor that inhibits NFKB and RIGI-like receptor (RLR) signaling to prevent excessive inflammation and maintain homeostasis. Selective autophagy receptors such as SQSTM1/p62 and OPTN are phosphorylated by the kinase TBK1 to stimulate their selective autophagy function. However, it is unknown if TAX1BP1 is regulated by TBK1 or other kinases under basal conditions or during RNA virus infection. Here, we found that TBK1 and IKBKE/IKKi function redundantly to phosphorylate TAX1BP1 and regulate its autophagic turnover through canonical macroautophagy. TAX1BP1 phosphorylation promotes its localization to lysosomes, resulting in its degradation. Additionally, we found that during vesicular stomatitis virus infection, TAX1BP1 is targeted to lysosomes in an ATG8-family protein-independent manner. Furthermore, TAX1BP1 plays a critical role in the clearance of MAVS aggregates, and phosphorylation of TAX1BP1 controls its MAVS aggrephagy function. Together, our data support a model whereby TBK1 and IKBKE license TAX1BP1-selective autophagy function to inhibit MAVS and RLR signaling.Abbreviations: ATG: autophagy related; BafA1: bafilomycin A1; CALCOCO2: calcium binding and coiled-coil domain 2; GFP: green fluorescent protein; IFA: indirect immunofluorescence assay; IFN: interferon; IκB: inhibitor of nuclear factor kappa B; IKK: IκB kinase; IRF: interferon regulatory factor; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; MEF: mouse embryonic fibroblast; MOI: multiplicity of infection; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; NFKB: nuclear factor kappa B; OPTN: optineurin; Poly(I:C): polyinosinic-polycytidylic acid; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SDD-AGE: semi-denaturing detergent-agarose gel electrophoresis; SeV: Sendai virus; SLR: SQSTM1-like receptor; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TNF: tumor necrosis factor; TRAF: TNF receptor associated factor; VSV: vesicular stomatitis virus; ZnF: zinc finger.

Regional and socioeconomic disparities in calcium scans.

INTRODUCTION: Disparities in cardiovascular care are well recognized, with socioeconomic status being one of the strongest determinants of cardiovascular disease outcomes. This study evaluates whether these disparities translate to coronary artery calcium (CAC) scan utilization. Specifically, we aim to describe regional variation and socioeconomic variables that impact CAC utilization across the United States relative to the prevalence of coronary artery disease (CAD) and related comorbidities. METHODS: This cross-sectional study integrates county-level CAC utilization with CAD prevalence and publicly available socioeconomic variables including self-identified ethnicity, education, and adjusted gross income. CAC utilization rates were sourced from 2022 hospital commercial claims, outpatient Medicare service claims, and independent imaging center claims. Heart disease prevalence and socioeconomic variables were extracted from the Centers for Disease Control and Prevention and the National Center for Chronic Disease Prevention and Health Promotion. Adjusted gross income per capita was gathered from Internal Revenue Service data. RESULTS: CAC utilization was evaluated across 808 counties within the United States, representing 600,379 claims. Median utilization was 1.62 scans per 1,000 persons with a range of 0.03 to 104.39. The West had the highest CAC scan utilization rate (median 3.09 scans per 1,000 persons) with a CAD prevalence of 548 per 100,000 persons. In contrast, the Midwest had the lowest utilization rate (median 1.24 scans per 1,000 persons) with a CAD prevalence of 635 per 100,000 persons. Socioeconomic factors that favor higher CAC utilization include a larger density of White/Caucasian ethnicity (p = 0.007) and a higher adjusted gross income per capita (p = 0.006). Counties with the lowest rates of CAC utilization have a higher population of African Americans (p <0.001) and a higher proportion of females (p <0.001). CONCLUSION: This analysis highlights regional and socioeconomic differences in CAC utilization in the United States. Under-represented ethnicities such as African Americans have among the lowest rates of CAC utilization despite having a higher burden and mortality from heart disease. Discordance between CAC utilization, heart disease prevalence and socioeconomic status reveals a need for targeted interventions and policies aimed at mitigating structural barriers that perpetuate health inequities.

Evaluation of stable angina by coronary computed tomographic angiography versus standard of care: A systematic review and meta-analysis.

INTRODUCTION: There is limited data comparing Coronary Computed Tomography Angiography (CCTA) versus the usual Standard of care (SOC) in patients with suspected stable coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis to compare CCTA versus SOC in patients with stable CAD. METHODS: We searched multiple databases for randomized controlled trials (RCTs) comparing CCTA with SOC, which included various functional testing approaches for evaluating stable CAD. We used a random-effects model to calculate risk ratios (RRs) with 95 % confidence intervals (CIs). Outcomes included all-cause mortality, myocardial infarction (MI), hospitalization for unstable angina (UA), invasive angiography, revascularization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). RESULTS: We identified 6 RCTs with 19,881 patients with stable CAD, of which 9995 underwent CCTA, and 9886 underwent SOC. There were no significant differences between CCTA and SOC in terms of all-cause mortality (RR: 0.91; 95 % CI: 0.70-1.19; p = 0.50), MI (RR: 0.78; 95 % CI: 0.58-1.05; p = 0.11), hospitalizations for UA (RR: 1.20; 95 % CI: 0.95-1.51;p = 0.12), invasive angiography (RR: 0.71; 95 % CI: 0.32-1.61; p = 0.42), revascularization (RR:1.25; 95 % CI: 0.83-1.89; p = 0.29), PCI (RR: 1.20; 95 % CI: 0.78-1.85; p = 0.40), and CABG rates (RR: 0.89; 95 % CI: 0.530-1.49; p = 0.65). CONCLUSION: In patients with stable CAD, CCTA is associated with similar outcomes compared to the usual Standard of care. Given its potential to quickly rule out severe obstructive disease, its ability to provide non-invasive physiology and identify non-obstructive CAD with plaque information makes it an attractive addition to the available armamentarium to evaluate chest pain.

Phosphorylation of aryl hydrocarbon receptor interacting protein by TBK1 negatively regulates IRF7 and the type I interferon response.

The innate antiviral response to RNA viruses is initiated by sensing of viral RNAs by RIG-I-like receptors and elicits type I interferon (IFN) production, which stimulates the expression of IFN-stimulated genes that orchestrate the antiviral response to prevent systemic infection. Negative regulation of type I IFN and its master regulator, transcription factor IRF7, is essential to maintain immune homeostasis. We previously demonstrated that AIP (aryl hydrocarbon receptor interacting protein) functions as a negative regulator of the innate antiviral immune response by binding to and sequestering IRF7 in the cytoplasm, thereby preventing IRF7 transcriptional activation and type I IFN production. However, it remains unknown how AIP inhibition of IRF7 is regulated. We show here that the kinase TBK1 phosphorylates AIP and Thr40 serves as the primary target for TBK1 phosphorylation. AIP Thr40 plays critical roles in regulating AIP stability and mediating its interaction with IRF7. The AIP phosphomimetic T40E exhibited increased proteasomal degradation and enhanced interaction with IRF7 compared with wildtype AIP. AIP T40E also blocked IRF7 nuclear translocation, which resulted in reduced type I IFN production and increased viral replication. In sharp contrast, AIP phosphonull mutant T40A had impaired IRF7 binding, and stable expression of AIP T40A in AIP-deficient mouse embryonic fibroblasts elicited a heightened type I IFN response and diminished RNA virus replication. Taken together, these results demonstrate that TBK1-mediated phosphorylation of AIP at Thr40 functions as a molecular switch that enables AIP to interact with and inhibit IRF7, thus preventing overactivation of type I IFN genes by IRF7.

The role of BST4 in the pyrenoid of Chlamydomonas reinhardtii.

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2-concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid-membranes called pyrenoid tubules, proposed to deliver CO2. In the model alga Chlamydomonas reinhardtii (Chlamydomonas), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules and heterologous expression of BST4 in Arabidopsis thaliana did not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonas bst4 mutant did not show impaired growth at air level CO2. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we show that bst4 displays a transiently lower thylakoid lumenal pH during dark to light transition compared to control strains. When acclimated to high light, bst4 had sustained higher NPQ and elevated levels of light-induced H2O2 production. We conclude that BST4 is not a tethering protein, but rather is an ion channel involved in lumenal pH regulation possibly by mediating bicarbonate transport across the pyrenoid tubules.

Chloroplast magnesium transporters play essential but differential roles in maintaining magnesium homeostasis.

Magnesium (Mg2+) is essential for photosynthesis in the chloroplasts of land plants and algae. Being the central ion of chlorophyll, cofactor and activator of many photosynthetic enzymes including RuBisCO, magnesium-deficient plants may suffer from leaf chlorosis symptoms and retarded growth. Therefore, the chloroplast Mg2+ concentration is tightly controlled by magnesium transport proteins. Recently, three different transporters from two distinct families have been identified in the chloroplast inner envelope of the model plant Arabidopsis thaliana: MGT10, MGR8, and MGR9. Here, we assess the individual roles of these three proteins in maintaining chloroplast Mg2+ homeostasis and regulating photosynthesis, and if their role is conserved in the model green alga Chlamydomonas reinhardtii. Phylogenetic analysis and heterologous expression revealed that the CorC-like MGR8 and MGR9 transport Mg2+ by a different mechanism than the CorA-like MGT10. MGR8 and MGT10 genes are highest expressed in leaves, indicating a function in chloroplast Mg2+ transport. MGR9 is important for chloroplast function and plant adaptation in conditions of deficiency or excess of Mg2+. Transmission electron microscopy indicated that MGT10 plays a differential role in thylakoid stacking than MGR8 and MGR9. Furthermore, we report that MGR8, MGR9, and MGT10 are involved in building up the pH gradient across the thylakoid membrane and activating photoprotection in conditions of excess light, however the mechanism has not been resolved yet. While there are no chloroplast MGR-like transporters in Chlamydomonas, we show that MRS4 is a homolog of MGT10, that is required for photosynthesis and cell growth. Taken together, our findings reveal that the studied Mg2+ transporters play essential but differential roles in maintaining chloroplast Mg2+ homeostasis.

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE.

Aims: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. Methods and Results: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort. Conclusion: Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response.

Two-phase microalgae cultivation for RAS water remediation and high-value biomass production.

The overall goal of this study was to provide solutions to innovative microalgae-based technology for wastewater remediation in a cold-water recirculating marine aquaculture system (RAS). This is based on the novel concept of integrated aquaculture systems in which fish nutrient-rich rearing water will be used for microalgae cultivation. The produced biomass can be used as fish feed, while the cleaned water can be reused, to create a highly eco-sustainable circular economy. Here, we tested three microalgae species Nannochloropis granulata (Ng), Phaeodactylum tricornutum (Pt), and Chlorella sp (Csp) for their ability to remove nitrogen and phosphate from the RAS wastewater and simultaneously produce high-value biomass, i.e., containing amino acids (AA), carotenoids, and polyunsaturated fatty acids (PUFAs). A high yield and value of biomass were achieved for all species in a two-phase cultivation strategy: i) a first phase using a medium optimized for best growth (f/2 14x, control); ii) a second "stress" phase using the RAS wastewater to enhance the production of high-value metabolites. Ng and Pt performed best in terms of biomass yield (i.e., 5-6 g of dry weight, DW.L-1) and efficient cleaning of the RAS wastewater from nitrite, nitrate, and phosphate (i.e., 100% removal). Csp produced about 3 g L-1 of DW and reduced efficiently only nitrate, and phosphate (i.e., about 76% and 100% removal, respectively). The biomass of all strains was rich in protein (30-40 % of DW) containing all the essential AA except Methionine. The biomass of all three species was also rich in PUFAs. Finally, all tested species are excellent sources of antioxidant carotenoids, including fucoxanthin (Pt), lutein (Ng and Csp) and ß-carotene (Csp). All tested species in our novel two-phase cultivation strategy thus showed great potential to treat marine RAS wastewater and provide sustainable alternatives to animal and plant proteins with extra added values.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Extent of subclinical atherosclerosis on coronary computed tomography and impact of statins in patients with diabetes without known coronary artery disease: Results from CONFIRM registry.

BACKGROUND: Absence of subclinical atherosclerosis is considered safe to defer statin therapy in general population. However, impact of statins on atherosclerotic cardiovascular disease in patients with diabetes stratified by coronary artery calcium (CAC) scores and extent of non-obstructive CAD on coronary computed tomography angiography (CCTA) has not been evaluated. METHODS: CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multi-center Registry) study enrolled consecutive adults 18 years of age between 2005 and 2009 who underwent 364-detector row CCTA for suspected CAD. The long-term registry includes data on 12,086 subjects who underwent CCTA at 17 centers in 9 countries. In this sub-study of CONFIRM registry, patients with diabetes mellitus (DM) and without diabetes mellitus with normal CCTA or non-obstructive plaque (<50 % diameter stenosis) for whom data on baseline statin use was available were included. CAC score was calculated using Agatston score. The magnitude of non-obstructive coronary artery disease on CCTA was quantified using segment involvement score (SIS). Primary outcome was major cardiovascular events (MACE) which included all-cause mortality, myocardial infarction, and target vessel re-vascularization. RESULTS: A total of 7247 patients (Mean age 56.8 years) with a median follow up of 5 years were included. For DM patients, baseline statin therapy significantly reduced MACE for patients with CAC ≥100 (HR: 0.24; 95 % CI 0.07-0.87; p = 0.03) and SIS≥3 (HR: 0.23; 95 % CI 0.06-0.83; p = 0.024) compared to those not on statin therapy. Among Diabetics with lower CAC (<100) and SIS (≤3) scores, MACE was similar in statin and non-statin groups. In contrast, among non-DM patients, MACE was similar in statin and no statin groups irrespective of baseline CAC (1-99 or ≥100) and SIS. CONCLUSION: In this large multicenter cohort of patients, the presence and extent of subclinical atherosclerosis as assessed by CAC and SIS identified patients most likely to derive benefit from statin therapy.

Harnessing imaging biomarkers to refine individualized cardiovascular disease risk: a case-based discussion.

Traditional models of cardiovascular risk assessment rely on population-level risk factors and may not accurately capture individualized risk. Imaging biomarkers such as plaque characterization and pericoronary fat inflammation may offer refined risk prediction and allow physicians to personalize care-plans for cardiovascular disease prevention. The integration of plaque morphology and pericoronary inflammation into clinical care is highlighted using a case-based discussion. This article reviews the existing body of evidence supporting the use of novel biomarkers in an individualized comprehensive risk assessment algorithm.

Mixotrophy in a Local Strain of Nannochloropsis granulata for Renewable High-Value Biomass Production on the West Coast of Sweden

A local strain of Nannochloropsis granulata (Ng) has been reported as the most productive microalgal strain in terms of both biomass yield and lipid content when cultivated in photobioreactors that simulate the light and temperature conditions during the summer on the west coast of Sweden. To further increase the biomass and the biotechnological potential of this strain in these conditions, mixotrophic growth (i.e., the simultaneous use of photosynthesis and respiration) with glycerol as an external carbon source was investigated in this study and compared with phototrophic growth that made use of air enriched with 1-2% CO2. The addition of either glycerol or CO2-enriched air stimulated the growth of Ng and theproduction of high-value long-chain polyunsaturated fatty acids (EPA) as well as the carotenoid canthaxanthin. Bioassays in human prostate cell lines indicated the highest antitumoral activity for Ng extracts and fractions from mixotrophic conditions. Metabolomics detected betaine lipids specifically in the bioactive fractions, suggesting their involvement in the observed antitumoral effect. Genes related to autophagy were found to be upregulated by the most bioactive fraction, suggesting a possible therapeutic target against prostate cancer progression. Taken together, our results suggest that the local Ng strain can be cultivated mixotrophically in summer conditions on the west coast of Sweden for the production of high-value biomass containing antiproliferative compounds, carotenoids, and EPA.

Radiation Doses in Patients Undergoing Computed Tomographic Coronary Artery Calcium Evaluation With a 64-Slice Scanner Versus a 256-Slice Scanner.

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression. The mean dose-length product was 21% lower in the study group than in the control group (60.2 ± 27 vs 75.9 ± 22.6 mGy·cm; P <0.001) and also in each body mass index subgroup. Similarly, the mean effective radiation dose was 21% lower in the study group (0.84 ± 0.38 vs 1.06 ± 0.32 mSv) and lower in each weight subgroup. After adjustment for sex, women in the study group had a lower dose-length product (50.4 ± 23.4 vs 64.7 ± 27.6 mGy·cm) than men did and received a lower effective dose (0.7 ± 0.32 vs 0.9 ± 0.38 mSv) (P=0.009). As body mass index and waist circumference increased, so did doses for both scanners. Our study group was exposed to radiation doses lower than the previously determined standard of 1 mSv, even after adjustment for body mass index and waist circumference. In 256-slice scanning for coronary artery calcium, radiation doses are now similar to those in lung cancer screening and mammography.

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

OBJECTIVE: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. METHODS: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. RESULTS: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. CONCLUSION: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

De-risking primary prevention: role of imaging.

Atherosclerotic cardiovascular disease (ASCVD) is a common disease among the general population, and includes four major areas: (1) coronary heart disease (CHD), manifested by stable angina, unstable angina, myocardial infarction (MI), heart failure, and coronary death; (2) cerebrovascular disease, manifested by transient ischemia attack and stroke; (3) peripheral vascular disease, manifested by claudication and critical limb ischemia; and (4) aortic atherosclerosis and aortic aneurysm (thoracic and abdominal). CHD remains the leading cause of death for both men and women in the United States. So, it is imperative to identify people at risk of CHD and provide appropriate medical treatment or intervention to prevent serious complications and outcomes including sudden cardiac death. Coronary artery calcification (CAC) is a marker of subclinical coronary artery disease. Therefore, coronary artery calcium score is an important screening method for Coronary artery disease (CAD). In this article, we performed a comprehensive review of current literatures and studies assessing the prognostic value of CAC for future cardiovascular disease (CVD) events. We searched PubMed, MEDLINE, Google Scholar, and Cochrane library. We also reviewed the 2018 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the assessment of CVD risk. A CAC score of zero corresponds to very low CVD event rates (∼1% per year) and hence a potent negative risk marker. This has been referred to as the 'power of zero' and affords the lowest risk of any method of risk calculation. It is now indicated in the 2018 ACC/AHA Cholesterol guidelines to be used to avoid statins for 5-10 years after a score of zero, and then re-assess the patient.

Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury.

A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays-such as prothrombin time, partial thromboplastin time, and international normalized ratio-have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.

Valve-in-valve transcatheter aortic valve replacement versus redo surgical valve replacement for degenerated bioprosthetic aortic valve: An updated meta-analysis comparing midterm outcomes.

BACKGROUND: Redo surgical aortic valve replacement (redo SAVR) and valve-in-valve transcatheter aortic valve replacement (ViV TAVR) are the two treatment strategies available for patients with severe symptomatic bioprosthetic aortic valve dysfunction. Herein, we performed a systematic review and meta-analysis comparing both early and mid-term outcomes of ViV TAVR versus redo SAVR in patients with bioprosthetic aortic valve disease. METHODS: PubMed, Cochrane reviews, and Google scholar electronic databases were searched and studies comparing ViV TAVR versus redo SAVR were included. The primary outcome of interest was mid-term (1-5 years) and 1-year all-cause mortality. Secondary outcomes included were 30-day all-cause mortality, myocardial infarction, pacemaker implantation, stroke, acute kidney injury, major or life-threatening bleeding, and postprocedural aortic valve gradients. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CIs) were calculated for all outcomes using the DerSimonian-Laird random-effects model. RESULTS: Nine observational studies with a total of 2,891 individuals and mean follow-up of 26 months met the inclusion criteria. There is no significant difference in mid-term and 1-year mortality between ViV-TAVR and redo SAVR groups with RR of 1.15 (95% CI 0.99-1.32; p = .06) and 1.06 (95% CI 0.69-1.61; p = .8). 30-day mortality rate was significantly lower in ViV-TAVR group with RR of 0.65 (95% CI 0.45-0.93; p = .02). ViV-TAVR group had lower 30-day bleeding, length of stay, and higher postoperative gradients. CONCLUSION: Our study demonstrates a lower 30-day mortality and similar 1-year and mid-term mortality for ViV TAVR compared to redo SAVR despite a higher baseline risk. Given these findings and the ongoing advances in the transcatheter therapeutics, VIV TAVR should be preferred over redo SAVR particularly in those at intermediate-high surgical risk.